Effects of Yishentongluo recipe on Nrf2 and HO-1 pathway activation leading to reduction of oxidative stress and kidney fibrosis in membranous nephropathy rat model / Efectos de la receta de Yishentongluo sobre la activación de las vías Nrf2 y HO-1 que conducen a la reducción del estrés oxidativo y fibrosis renal en un modelo de rata con nefropatía membranosa

This study investigated Yishentongluo Recipe (YSTLF) effects on renal oxidative stress and fibrosis in membranous nephropathy (MN) rats. MN was induced by cationized bovine serum albumin injection. Rats were divided into control, MN, YSTLF, and benazepril groups. After four weeks of treatment, urine protein levels (UTP), serum total cholesterol (TC), triglycerides (TG), total protein (TP), and albumin (ALB) were assessed. Kidney microstructure, IgG immune complex deposition, and protein expressions of superoxide dismutase (SOD), malondialdehyde (MDA), transforming growth factor ß1 (TGF-ß1), collagen I (Collagen-I), α-smooth muscle actin (α-SMA), nuclear factor E2-related factor (Nrf2), haem oxygenase 1 (HO-1), and NADPH oxidase 4 (NOX4) were evaluated. YSTLF and BNPL treatments reduced UTP, TC, TG, increased TP and ALB levels, downregulated TGF-ß1, Collagen-I, and α-SMA, and upregulated Nrf2, HO-1, and NOX4. YSTLF partially reversed SOD reduction and MDA elevation, suggesting its efficacy in alleviating renal oxidative stress and fibrosis in MN rats via Nrf2/HO-1 signaling pathway activation.

Este estudio investigó los efectos de la receta Yishentongluo (YSTLF) sobre el estrés oxidativo renal y la fibrosis en ratas con nefropatía membranosa (MN). La MN se indujo mediante inyección de albúmina sérica bovina cationizada. Las ratas se dividieron en grupos de control, MN, YSTLF y benazepril. Después de cuatro semanas de tratamiento, se evaluaron los niveles de proteína en orina (UTP), colesterol total (CT), triglicéridos (TG), proteína total (TP) y albúmina (ALB) en suero. Se evaluaron la microestructura renal, el depósito de complejos inmunes IgG y expresiones proteicas de superóxido dismutasa (SOD), malondialdehído (MDA), factor de crecimiento transformante ß1 (TGF-ß1), colágeno I (Colágeno-I), α-actina del músculo liso (α-SMA), el factor nuclear E2 (Nrf2), la hemooxigenasa 1 (HO-1) y la NADPH oxidasa 4 (NOX4). Los tratamientos con YSTLF y BNPL redujeron UTP, TC, TG, aumentaron los niveles de TP y ALB, regularon negativamente TGF-ß1, Colágeno-I y α-SMA, y regularon positivamente Nrf2, HO-1 y NOX4. YSTLF revirtió parcialmente la reducción de SOD y la elevación de MDA, lo que sugiere su eficacia para aliviar el estrés oxidativo renal y la fibrosis en ratas MN mediante la activación de la vía de señalización Nrf2/HO-1.

Morphological and Morphometric Analysis, Apoptosis and Oxidative Stress Study in Hep 2 Cells Treated by Resveratrol or Quercetine / Análisis Morfológico y Morfométrico, Estudio de Apoptosis y Estrés Oxidativo en Células Hep 2 Tratadas con Resveratrol o Quercetina

SUMMARY: Resveratrol (RES) and quercetine (QRC), is a promising agent relevant for both cancer chemoprevention and treatment via several signaling pathways, involved in their anticancer activity related to its chemotherapeutic potential, associated with the induction of ROS generation in cancer cells, leading to apoptosis. In our study, we have summarized the mechanisms of action of RES and QRC, and their pharmacological implications and potential therapeutic applications in cancer therapy. After treatment of Hep 2 cells with QRC or RES, the death pathways such as the cytochrome c release, ERK1/2 and IRS-1 pathways were upregulated, while cell survival pathway, including PI3K/AKT were downregulated. The RES and QRC caused oncosis, cells hypertrophy, hypercondensatin of chromatin, rupture of the plasma membrane and nuclear membrane, and formation of apoptotic bodies. Morphometric measurements of some cellular and nuclear parameters showed that RES and QRC induced an increase in cells and nuclear size, the nucleocytoplasmic ratio remained below 1 (N-Cyt R < 1), sign of low nuclear activity. The RES and QRC induced apoptosis of Hep2 cells by increasing of oxidative stress markers, MDA, and by modulating detoxifying enzymes, CAT and SOD. Our study results prove antiproliferative and proapoptotic properties of quercetin and resveratrol with regard to larynx cancer.

Resveratrol (RES) y quercetina (QRC), es un agente prometedor y relevante tanto para la quimioprevención como para el tratamiento del cáncer a través de varias vías de señalización, involucrado en su actividad anticancerígena relacionada con su potencial quimioterapéutico, asociado con la inducción de la generación de especies reactivas del oxígeno (ROS) en células cancerosas, lo que lleva a apoptosis. En nuestro estudio, hemos resumido los mecanismos de acción de RES y QRC, y sus implicaciones farmacológicas y posibles aplicaciones terapéuticas en la terapia del cáncer. Después del tratamiento de las células Hep 2 con QRC o RES, las vías de muerte, tal como la liberación de citocromo c, las vías ERK1/2 e IRS-1, se regulaban positivamente, mientras que la vía de supervivencia celular, incluida PI3K/AKT, se regulaba negativamente. El RES y el QRC provocaron oncosis, hipertrofia celular, hipercondensación de la cromatina, rotura de la membrana plasmática y nuclear y formación de cuerpos apoptóticos. Las mediciones morfométricas de algunos parámetros celulares y nucleares mostraron que RES y QRC indujeron un aumento en las células y el tamaño nuclear, la proporción nucleocitoplasmática se mantuvo por debajo de 1 (N- Cyt R <1), signo de baja actividad nuclear. RES y QRC indujeron la apoptosis de las células Hep2 aumentando los marcadores de estrés oxidativo, MDA, y modulando las enzimas desintoxicantes, CAT y SOD. Los resultados de nuestro estudio demuestran las propiedades antiproliferativas y proapoptóticas de la quercetina y el resveratrol con respecto al cáncer de laringe.

An Assessment of Ankle Function, Oxidative Damage, and Inflammatory Factor Levels in Minimally Invasive Ankle Joint Fusion Surgery for the Treatment of Traumatic Ankle Osteoarthritis

SUMMARY: Traumatic ankle osteoarthritis is a degenerative condition resulting from traumatic injuries. The objective of this study was to evaluate the impact of minimally invasive ankle joint fusion surgery on ankle function, oxidative damage, and inflammatory factor levels in traumatic ankle osteoarthritis patients. A total of 112 traumatic ankle osteoarthritis patients treated in our hospital from January 2022 to January 2023 were enrolled. They were randomly rolled into a control group (Group C) and an experimental group (Group E), with the former undergoing conventional open ankle joint fusion surgery and the latter receiving minimally invasive ankle joint fusion surgery. A comparison was made between the two groups based on American Orthopedic Foot and Ankle Society (AOFAS), bony fusion rates, and visual analog scale (VAS) scores at pre-operation, and at 1, 2, and 3 months post-operation. Additionally, serum oxidative damage indicators and inflammatory factor levels were measured to evaluate the recovery effects in both groups. Relative to Group C, Group E showed drastically increased AOFAS scores and bony fusion rates (P<0.05), as well as greatly decreased VAS scores (P<0.05). Moreover, Group E exhibited more pronounced improvements in oxidative damage indicators and inflammatory factors versus Group C (P<0.05). Minimally invasive ankle joint fusion surgery drastically improves ankle function in traumatic ankle osteoarthritis patients and reduces levels of oxidative damage and inflammatory response. This provides an important clinical treatment option.

La osteoartritis traumática del tobillo es una afección degenerativa resultante de lesiones traumáticas. El objetivo de este estudio fue evaluar el impacto de la cirugía mínimamente invasiva de fusión de la articulación talocrural sobre la función del tobillo, el daño oxidativo y los niveles de factor inflamatorio en pacientes con osteoartritis traumática del tobillo. Se inscribieron un total de 112 pacientes con artrosis traumática de tobillo tratados en nuestro hospital desde enero de 2022 hasta enero de 2023. Fueron divididos aleatoriamente en un grupo de control (Grupo C) y un grupo experimental (Grupo E), donde el primero se sometió a una cirugía de fusión de la articulación talocrural abierta convencional y el segundo recibió una cirugía de fusión de la articulación talocrural mínimamente invasiva. Se realizó una comparación entre los dos grupos según la Sociedad Estadounidense de Ortopedia de Pie y Tobillo (AOFAS), las tasas de fusión ósea y las puntuaciones de la escala visual analógica (EVA) antes de la operación y 1, 2 y 3 meses después de la operación. Además, se midieron los indicadores de daño oxidativo sérico y los niveles de factor inflamatorio para evaluar los efectos de la recuperación en ambos grupos. En relación con el grupo C, el grupo E mostró puntuaciones AOFAS y tasas de fusión ósea drásticamente aumentadas (P <0,05), así como puntuaciones VAS muy disminuidas (P <0,05). Además, el grupo E exhibió mejoras más pronunciadas en los indicadores de daño oxidativo y factores inflamatorios en comparación con el grupo C (P <0,05). La cirugía de fusión de la articulación talocrural mínimamente invasiva mejora drásticamente la función del tobillo en pacientes con osteoartritis traumática del tobillo y reduce los niveles de daño oxidativo y la respuesta inflamatoria. Esto proporciona una importante opción de tratamiento clínico.

Association of IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with COPD: a cross-sectional study / Asociación de los genotipos de IGF-1 e IGF-2 con la fuerza muscular respiratoria en individuos con EPOC: estudio transversal

INTRODUCTION: Chronic obstructive pulmonary disease is a systemic disease characterized not only by respiratory symptoms but also by physical deconditioning and muscle weakness. One prominent manifestation of this disease is the decline in respiratory muscle strength. Previous studies have linked the genotypes of insulin-like growth factor 1 and 2 (IGF-1 and IGF-2) to muscle weakness in other populations without this disease. However, there is a notable knowledge gap regarding the biological mechanisms underlying respiratory muscle weakness, particularly the role of IGF-1 and IGF-2 genotypes in this pulmonary disease. Therefore, this study aimed to investigate, for the first time, the association between IGF-1 and IGF-2 genotypes with respiratory muscle strength in individuals with chronic obstructive pulmonary disease. In addition, we analyzed the relationship between oxidative stress, chronic inflammation, and vitamin D with respiratory muscle strength. METHODS: A cross sectional study with 61 individuals with chronic obstructive pulmonary disease. Polymerase chain reaction of gene polymorphisms IGF-1 (rs35767) and IGF-2 (rs3213221) was analyzed. Other variables, related to oxidative stress, inflammation and Vitamin D were dosed from peripheral blood. Maximal inspiratory and expiratory pressure were measured. RESULTS: The genetic polymorphisms were associated with respiratory muscle strength ( 3.0 and 3.5; = 0.57). Specific genotypes of IGF-1 and IGF-2 presented lower maximal inspiratory and expiratory pressure (<0.05 for all). Oxidative stress, inflammatory biomarkers, and vitamin D were not associated with respiratory muscle strength. CONCLUSION: The polymorphisms of IGF-1 and IGF-2 displayed stronger correlations with respiratory muscle strength compared to blood biomarkers in patients with chronic obstructive pulmonary disease. Specific genotypes of IGF-1 and IGF-2 were associated with reduced respiratory muscle strength in this population.

INTRODUCCIÓN: La enfermedad pulmonar obstructiva crónica es una enfermedad sistémica caracterizada no solo por síntomas respiratorios, sino también por el deterioro físico y la debilidad muscular. Una manifestación destacada de esta enfermedad es el declive en la fuerza de los músculos respiratorios. Estudios previos han vinculado los genotipos de factor de crecimiento insulínico 1 y 2 (IGF-1 e IGF-2) con la debilidad muscular en poblaciones sin esta enfermedad. Sin embargo, existe un vacío de conocimiento con respecto a los mecanismos biológicos subyacentes a la debilidad de los músculos respiratorios, en particular el papel de los genotipos IGF-1 e IGF-2 en esta enfermedad pulmonar. Por lo tanto, este estudio tuvo como objetivo investigar, por primera vez, la asociación de los genotipos IGF-1 e IGF-2 con la fuerza de los músculos respiratorios en individuos con enfermedad pulmonar obstructiva crónica. Además, analizamos la relación entre el estrés oxidativo, la inflamación crónica y la vitamina D con la fuerza de los músculos respiratorios. MÉTODOS: Un estudio transversal con 61 individuos con enfermedad pulmonar obstructiva crónica. Se analizó la reacción en cadena de la polimerasa de los polimorfismos genéticos IGF-1 (rs35767) e IGF-2 (rs3213221). Otras variables relacionadas con el estrés oxidativo, la inflamación y la vitamina D se dosificaron a partir de muestras de sangre periférica. Se midieron las presiones inspiratorias y espiratorias máximas. RESULTADOS: Los polimorfismos genéticos están asociados con la fuerza de los músculos respiratorios (F: 3.0 y 3.5; R2= 0.57). Genotipos específicos de IGF-1 e IGF-2 presentaron bajos valores en las presiones inspiratorias y espiratorias (p<0.05 en todos los casos). El estrés oxidativo, los biomarcadores inflamatorios y la vitamina D no se asociaron con la fuerza de los músculos respiratorios. CONCLUSIÓN: Los polimorfismos de IGF-1 e IGF-2 mostraron correlaciones más sólidas con la fuerza de los músculos respiratorios en pacientes con enfermedad pulmonar obstructiva crónica en comparación con los biomarcadores sanguíneos. Genotipos específicos de IGF-1 e IGF-2 se asociaron con una disminución de la fuerza de los músculos respiratorios en esta población.

Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice / 神经科学通报·英文版

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Oxidative and osmotolerant effects in Salvator merianae (Squamata: Teiidae) red blood cells during hibernation / Efeitos de oxidação e osmotolerância dos eritrócitos de Salvator merianae (Squamata: Teiidae) durante a hibernação

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.

Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

Development of chitosan based microencapsulated spray dried powder of tuna fish oil: oil load impact and oxidative stability / Desenvolvimento de pó microencapsulado por pulverização de óleo de atum à base de quitosana: impacto da carga de óleo e estabilidade oxidativa

Abstract The impact of fish oil concentration on the oxidative stability of microcapsules through the spray drying process using chitosan and maltodextrin as wall material was studied. Emulsions were prepared with different Tuna fish oil (TFO) content (TFO-10%, TFO20%, TF030% TF0-40%) while wall material concentration was kept constant. Microencapsulated powder resulting from emulsion prepared with high fish oil load have high moisture content, wettability, total oil and low encapsulation efficiency, hygroscopicity and bulk tapped density. Oxidative stability was evaluated periodically by placing microcapsules at room temperature. Microcapsules prepared with TFO-10% presented high oxidative stability in terms of peroxide value (2.94±0.04) and anisidine value (1.54±0.02) after 30 days of storage. It was concluded that optimal amounts of fish oil for microencapsulation are 10% and 20% using chitosan and maltodextrin that extended its shelf life during study period.

Resumo Foi estudado o impacto da concentração de óleo de peixe na estabilidade oxidativa de microcápsulas por meio do processo de secagem por atomização, utilizando quitosana e maltodextrina como material de parede. As emulsões foram preparadas com diferentes teores de óleo de atum (TFO) (TFO-10%, TFO20%, TF030% TF0-40%), enquanto a concentração de material de parede foi mantida constante. O pó microencapsulado resultante da emulsão preparada com alta carga de óleo de peixe tem alto teor de umidade, molhabilidade e óleo total e baixa eficiência de encapsulação, higroscopicidade e densidade extraída a granel. A estabilidade oxidativa foi avaliada periodicamente colocando microcápsulas à temperatura ambiente. As microcápsulas preparadas com TFO-10% apresentaram alta estabilidade oxidativa em termos de valor de peróxido (2,94 ± 0,04) e valor de anisidina (1,54 ± 0,02) após 30 dias de armazenamento. Concluiu-se que as quantidades ideais de óleo de peixe para microencapsulação são de 10% e 20% usando quitosana e maltodextrina que prolongaram sua vida útil durante o período de estudo.

Activation of M1 muscarinic acetylcholine receptors by proline-rich oligopeptide 7a (

Background: The bioactive peptides derived from snake venoms of the Viperidae family species have been promising as therapeutic candidates for neuroprotection due to their ability to prevent neuronal cell loss, injury, and death. Therefore, this study aimed to evaluate the cytoprotective effects of a synthetic proline-rich oligopeptide 7a (PRO-7a; <EDGPIPP) from Bothrops jararaca snake, on oxidative stress-induced toxicity in neuronal PC12 cells and astrocyte-like C6 cells. Methods: Both cells were pre-treated for four hours with different concentrations of PRO-7a, submitted to H2O2-induced damage for 20 h, and then the oxidative stress markers were analyzed. Also, two independent neuroprotective mechanisms were investigated: a) L-arginine metabolite generation via argininosuccinate synthetase (AsS) activity regulation to produce agmatine or polyamines with neuroprotective properties; b) M1 mAChR receptor subtype activation pathway to reduce oxidative stress and neuron injury. Results: PRO-7a was not cytoprotective in C6 cells, but potentiated the H2O2-induced damage to cell integrity at a concentration lower than 0.38 μM. However, PRO-7a at 1.56 µM, on the other hand, modified H2O2-induced toxicity in PC12 cells by restoring cell integrity, mitochondrial metabolism, ROS generation, and arginase indirect activity. The α-Methyl-DL-aspartic acid (MDLA) and L-NΩ-Nitroarginine methyl ester (L-Name), specific inhibitors of AsS and nitric oxide synthase (NOS), which catalyzes the synthesis of polyamines and NO from L-arginine, did not suppress PRO-7a-mediated cytoprotection against oxidative stress. It suggested that its mechanism is independent of the production of L-arginine metabolites with neuroprotective properties by increased AsS activity. On the other hand, the neuroprotective effect of PRO-7a was blocked in the presence of dicyclomine hydrochloride (DCH), an M1 mAChR antagonist. Conclusions: For the first time, this work provides evidence that PRO-7a-induced neuroprotection seems to be mediated through M1 mAChR activation in PC12 cells, which reduces oxidative stress independently of AsS activity and L-arginine bioavailability.(AU)

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Effects of vitamin D supplementation on oxidative stress biomarkers of Iranian women with polycystic ovary syndrome: a meta-analysis study

Abstract Objective To identify the impact of redox imbalance on the clinical evolution of patients with polycystic ovary syndrome and carry out a qualitative and quantitative projection of the benefits of vitamin D supplementation. Data sources Combinations of the keywords polycystic ovary syndrome, vitamin D, oxidative stress, reactive oxygen species, antioxidant, and free radicals were used in PubMed, Cochrane Library, LILACS, EMBASE, and Web of Science databases. The last search was conducted on August 22, 2023.Selection of studies: Based on the inclusion and exclusion criteria, studies were selected considering a low risk of bias, published in the last 5 years in English, which investigated the effects of vitamin D supplementation in women with PCOS, focusing on oxidative stress markers. Of the 136 articles retrieved, 6 intervention studies (445 women) were included. Data collection The risk of bias in included studies was assessed using the Jadad scale, and analysis and visualization of continuous data were performed using Review Manager 5.4.1, summarized as standardized mean differences (SMD) with confidence intervals (CI) of 95%. Data synthesis Vitamin D effectively reduced malondialdehyde (P=0.002) and total testosterone (P=0.0004) levels and increased total antioxidant capacity levels (P=0.01). Although possible improvements in the modified Ferriman-Gallwey hirsutism score, levels of sex hormone-binding globulin, and free androgen index were identified and the results were not statistically significant. Conclusion Vitamin D is a promising alternative for the treatment of PCOS with a positive influence on the oxidative, metabolic, and endocrine disorders of this syndrome.

Embryo development is impaired by sperm mitochondrial-derived ROS

BACKGROUND: Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. RESULTS: We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. CONCLUSION: Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.

Efectos de inducción recíproca entre periodontitis e hiposalivación: revisión de la literatura / Reciprocal induction effects between periodontitis and hyposalivation: a review of the literature

Muchas investigaciones se han ocupado de evaluar la vinculación entre las afecciones bucales y otras funciones o afecciones del organismo. Algunos de esos estudios han sentado precedentes acerca de la influencia mutua que puede existir entre la fun-cionalidad de las glándulas salivales y la enfermedad periodontal, y cómo la presencia de una condición puede modificar la evolución o inducir la aparición de la otra. El objetivo del presente trabajo es hacer una revisión bibliográfica de las publicaciones cientí-ficas que evalúan los efectos de inducción recíproca que existe entre la enfermedad periodontal y la hi-posalivación. Trabajos de nuestro grupo y de otros autores demuestran que la hiposalivación reduce la capacidad del organismo para defenderse contra las bacterias patógenas, mantener un ambiente sa-ludable y facilitar la cicatrización en la cavidad bu-cal, promoviendo los procesos de inflamación y daño tisular gingivoperiodontal. A su vez, varios estudios reportan que la enfermedad periodontal induce cam-bios en las glándulas salivales y altera el volumen de secreción salival. Por su parte, el sistema endo-cannabinoide (SEC) muestra estar involucrado tanto en el proceso de secreción salival como en la infla-mación y la reabsorción ósea presentes en la enfer-medad periodontal, en tanto que la activación de los mecanismos del SEC emerge como una de las vías a través de las cuales se desarrollaría el fenómeno de inducción recíproca (AU)

Many investigations have focused on evaluating the link between oral conditions and other functions or conditions of the body. Some of these studies have set precedents about the mutual influence that may exist between the functionality of the salivary glands and periodontal disease, and how the presence of one condition can modify the evolution or induce the appearance of the other. The objective of this work is to carry out a bibliographic review of scientific publications that evaluate the reciprocal induction effects that exist between periodontal disease and hyposalivation. Studies by our group and other authors show that hyposalivation reduces the capacity of the organism to defend itself against pathogenic bacteria, maintain a healthy environment and facilitate healing in the oral cavity, promoting inflammation and gingivoperiodontal tissue damage. In turn, several studies report that periodontal disease induces changes in the salivary glands and alters the volume of salivary secretion. In turn, the endocannabinoid system (ECS) is shown to be involved in the salivary secretion process as well as in the inflammation and bone resorption present in periodontal disease, while the activation of ECS mechanisms emerges as one of the pathways through which the reciprocal induction phenomenon would develop (AU)

Columbianadin ameliorates experimental acute reflux esophagitis in rats via suppression of NF-κB pathway

Purpose: Reflux esophagitis is a condition characterized by inflammation and irritation of the esophagus, resulting from the backflow of stomach acid and other gastric contents into the esophagus. Columbianadin is a coumarin derivative that exhibits anti-inflammatory and antioxidant effects. In this study, we tried to scrutinize the protective effect of Columbianadin against acute reflux esophagitis in rats. Methods: RAW 264.7 cells were utilized to assess cell viability and measure the production of inflammatory parameters. The rats received anesthesia, and reflux esophagitis was induced via ligation of pylorus and fore stomach and corpus junction. Rats received the oral administration of Columbianadin (25, 50 and 100 mg/kg) and omeprazole (20 mg/kg). The gastric secretion volume, acidity, and pH were measured. Additionally, the levels of oxidative stress parameters, cytokines, and inflammatory markers were determined. At the end of the study, mRNA expression was assessed. Results: Columbianadin remarkably suppressed the cell viability and production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and prostaglandin (PGE2). Columbianadin treatment remarkably suppressed the secretion of gastric volume, total acidity and enhanced the pH level in the stomach. Columbianadin remarkably altered the level of hydrogen peroxidase, free iron, calcium, and plasma scavenging activity, sulfhydryl group; oxidative stress parameters like malonaldehyde, glutathione, superoxide dismutase, catalase, glutathione peroxidase; inflammatory cytokines viz., TNF-α, IL-6, IL-1ß, IL-10, IL-17, and monocyte chemoattractant protein-1; inflammatory parameters including PGE2, iNOS, COX-2, and nuclear kappa B factor (NF-κB). Columbianadin remarkably (P < 0.001) suppressed the mRNA expression TNF-α, IL-6, IL-1ß and plasminogen activator inhibitor-1. Conclusions: Columbianadin demonstrated a protective effect against acute reflux esophagitis via NF-κB pathway.

XinJiaCongRongTuSiZiWan protects triptolide-induced rats from oxidative stress injury via mitophagy mediated PINK1/Parkin signaling pathway

Purpose: XinJiaCongRongTuSiZiWan (XJCRTSZW) is a traditional Chinese medicine compound for invigorating the kidney, nourishing blood, and promoting blood circulation. This study aimed to explore the effect of XJCRTSZW on triptolide (TP)-induced oxidative stress injury. Methods: Adult female Sprague-Dawley rats and human ovarian granulosa cell lines were treated with TP and XJCRTSZW. Hematoxylin and eosin staining, enzyme-linked immunosorbent assay, flow cytometry, CCK-8, JC-1 staining, transmission electron microscopy, reverse transcription-quantitative polymerase chain reaction, and Western blotting were performed in this study. Results: XJCRTSZW treatment observably ameliorated the TP-induced pathological symptoms. Furthermore, XJCRTSZW treatment observably enhanced the TP-induced reduction of estradiol, anti-Mullerian hormone, progesterone, superoxide dismutase, ATP content, mitochondrial membrane potential, p62, and Hsp60 mRNA, and protein levels in vivo and in vitro (p < 0.05). However, TP-induced elevation of follicle stimulating hormone and luteinizing hormone concentrations, malondialdehyde levels, reactive oxygen species levels, apoptosis rate, mitophagy, and the mRNA and protein expressions of LC3-II/LC3-I, PTEN-induced kinase 1 (PINK1), and Parkin were decreased (p < 0.05). In addition, XJCRTSZW treatment markedly increased cell viability in vitro (p < 0.05). Conclusions: XJCRTSZW protects TP-induced rats from oxidative stress injury via the mitophagy-mediated PINK1/Parkin pathway.

Eucommia granules activate Wnt/ß-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats

Purpose: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. Methods: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/ß-catenin pathway-related protein expression was detected using Western blot. Results: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/ß-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. Conclusions: EG may activate the Wnt/ß-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Dietary total antioxidant capacity, cardiovascular risk, and anthropometric obesity indices in hemodialysis patients: A case-control study / Capacidade antioxidante total da dieta, risco cardiovascular e índices antropométricos de obesidade em pacientes em hemodiálise: um estudo de caso-controle

ABSTRACT Objective: Oxidative stress is triggered by malnutrition and antioxidant losses due to dialysis in hemodialysis patients and thus, oxidative stress increases the risk of mortality in patients with cardiovascular disease and obesity. The study aims to determine differences in cardiovascular risk scores and obesity indices between hemodialysis and control groups and to examine the relationship between the tertiles of dietary total antioxidant capacity with cardiovascular risk, and obesity in hemodialysis and control groups. Methods: This is a cross-sectional case-control study involving hemodialysis patients (n=46) and healthy individuals (n=46). Participants' general characteristics were obtained via a questionnaire, and the Framingham Risk Score was calculated. The dietary total antioxidant capacity was calculated using two methods based on a seven-day food record. Obesity indices, such as Basal Metabolism Index and Body Shape Index, were calculated using anthropometric measurements. Results: The mean age of the participants was 51.1±10.4 years. In the hemodialysis group, obesity indices including body weight, Basal Metabolism Index, waist circumference, fat mass index, and fat-free mass index were lower, while Framingham Risk Score values ​​were higher than the control group (p<0.05). Energy-adjusted dietary total antioksidant capacity values were lower ​​in hemodialysis group, and most patients were in the low tertiles of Trolox equivalent antioxidant capacity, total radical-trapping antioxidant parameter, ferric reducing-antioxidant power and vitamin C equivalent antioxidant capacity (p<0.05). Conclusion: Providing hemodialysis patients with a healthy diet can increase the dietary total antioxidant capacity, and potentially reduce cardiovascular risk, and obesity indices.

RESUMO Objetivo: O estresse oxidativo é desencadeado pela desnutrição e perdas de antioxidantes devido à diálise em pacientes em hemodiálise, portanto, o estresse oxidativo aumenta o risco de mortalidade em pacientes com doenças cardiovasculares e obesidade. O estudo visa determinar as diferenças nos escores de risco cardiovascular e índices de obesidade entre os grupos de hemodiálise e controle, bem como examinar a relação entre os tercis da capacidade antioxidante total da dieta e o risco cardiovascular e obesidade nos grupos de hemodiálise e controle. Métodos: Este é um estudo transversal de caso-controle envolvendo pacientes em hemodiálise (n=46) e indivíduos saudáveis (n=46). As características gerais dos participantes foram obtidas por meio de um questionário, e o Escore de Risco de Framingham foi calculado. A capacidade antioxidante total da dieta foi calculada utilizando dois métodos baseados em um registro alimentar de sete dias. Índices de obesidade como o Índice de Metabolismo Basal e o Índice de Forma Corporal, foram calculados por meio de medidas antropométricas. Resultados: A média de idade dos participantes foi de 51.1±10.4 anos. No grupo de hemodiálise, os índices de obesidade, incluindo peso corporal, Índice de Metabolismo Basal, circunferência da cintura, índice de massa gorda e índice de massa livre de gordura, foram menores, enquanto os valores do Escore de Risco de Framingham foram maiores do que no grupo controle (p<0.05). Os valores de dTAC ajustados pela energia foram menores no grupo de foram hemodiálise, e a maioria dos pacientes estava nos tercis mais baixos de Capacidade antioxidante equivalente ao Trolox, parâmetro antioxidante total de captura de radicais, poder antioxidante redutor férrico e capacidade antioxidante equivalente à vitamina C (p <0.05). Conclusão: Fornecer aos pacientes em hemodiálise uma dieta saudável pode aumentar a capacidade antioxidante total da dieta, reduzindo potencialmente o risco cardiovascular e os índices de obesidade.

Is there a difference in the oxidative stress levels between type 2 diabetic individuals with and without periodontitis? Systematic review / Existe diferença nos níveis de estresse oxidativo entre indivíduos com diabetes tipo 2 com e sem periodontite? Revisão Sistemática

Objective: The authors' aim in this systematic review was to verify the scientific evidence for difference of oxidative stress biomarkers in individuals with type 2 diabetes mellitus with and without periodontitis. Material and Methods: Observational studies, baseline data of prospective and interventional studies were searched on the following databases: Virtual Health Library, Web of Science, PubMed, Embase, Scopus, Cochrane Library, Opengrey and Google Scholar. The electronic search was performed in June 01, 2020 until May 17, 2024 with alerts until June 01, 2024. The quality assessment and the certainty of the evidence of the included studies were evaluated through Fowkes and Fulton's checklist and GRADEpro Guideline Development Tool. Results: Of 988 relevant articles, the authors included 9 studies for the final analysis. Among those studies, 4 cross-sectional, 3 case-control, and 2 interventional studies were included. The analysis of non-randomized clinical trials properly reported most of the criteria analyzed in Summary questions (Bias, Confounding and Chance) as present in 3 studies. In six studies confounding factors were no detected. Due to the variation in the study results and clinical/methodological heterogeneity, a meta-analysis was not appropriate. The studies reported high concentrations of oxidizing agents and low antioxidants levels in individuals with type 2 diabetes mellitus and periodontitis when compared to with no periodontitis. Conclusion: Considering the few studies found, the methodological flaws, few markers studied and absence homogeneity in the evaluation of redox balance markers, as well as, the very low certainty of the evidence among included studies, it was not possible to determine whether there are or not differences in the oxidative stress levels in individuals with type 2 diabetes with and without periodontitis, and therefore, further prospective observational and interventional studies are recommended. (AU)

Objetivo: O objetivo dos autores nesta revisão sistemática foi verificar a evidência científica para a diferença de biomarcadores de estresse oxidativo em indivíduos com diabetes mellitus tipo 2 com e sem periodontite. Material e Métodos: estudos observacionais, dados de base de estudos prospectivos e intervencionistas foram pesquisados nas seguintes bases de dados: Biblioteca Virtual em Saúde, Web of Science, PubMed, Embase, Scopus, Cochrane Library, Opengrey e Google Scholar. A busca eletrônica foi realizada no período de 01 de junho de 2020 até 17 de maio de 2024, com alertas até 01 de junho de 2024. A avaliação da qualidade e a certeza da evidência dos estudos incluídos foi realizada através da lista de checagem Fowkes and Fulton's e da Ferramenta de desenvolvimento de diretrizes GRADEpro. Resultados: Dos 988 artigos relevantes, os autores incluíram 9 estudos para a análise final. Entre esses estudos, foram incluídos 4 estudos transversais, 3 de caso-controle e 2 de intervenção. A análise dos ensaios clínicos não randomizados relatou adequadamente a maioria dos critérios analisados nas questões resumo (Viés, Confundimento e Resultados ao caso) presentes em 3 estudos. Fatores de confusão não foram detectados em seis estudos. Devido à variação nos resultados do estudo e à heterogeneidade clínica/metodológica, não foi possível realizar uma meta-análise. Os estudos relataram altas concentrações de agentes oxidantes e baixos níveis de antioxidantes em indivíduos com diabetes mellitus tipo 2 e periodontite quando comparados a indivíduos sem periodontite. Conclusão: Considerando os poucos estudos encontrados, as falhas metodológicas, poucos marcadores estudados e ausência de homogeneidade na avaliação dos marcadores do balanço redox, bem como a baixíssima certeza da evidência entre os estudos incluídos, não foi possível determinar se há diferenças nos níveis de estresse oxidativo em indivíduos com diabetes tipo 2 associado e não à periodontite e, portanto, outras observações prospectivas e estudos de intervenção são recomendados (AU)

Aceite de rosa mosqueta (Rosa rubiginosa) disminuye marcadores inflamatorios en células hepáticas humanas HepG2 tratadas con lipopolisacárido / Rosa mosqueta (Rosa rubiginosa) oil decreases inflammatory markers in human liver cells HepG2 treated with lipopolysaccharide

La alteración de la microbiota intestinal es uno de los factores claves que afecta el inicio y la progresión de esteatosis hepática, al aumentar la permeabilidad intestinal e inducir un aumento circulante de la endotoxina lipopolisacárido (LPS). El LPS puede llegar al hígado a través de la vena porta, donde desencadena procesos inflamatorios y pro-oxidantes. Por otro lado, alimentos ricos en aceites esenciales podrían tener la capacidad de contrarrestar los efectos deletéreos del LPS a nivel hepático. El objetivo de este estudio fue evaluar el efecto del aceite de rosa mosqueta (ARM) en la prevención de procesos inflamatorios y oxidantes en hepatocitos humanos HepG2 tratados con LPS. Células HepG2 fueron expuestas a diferentes dosis de ARM (1,5, 3, 4,5, 6 y 7,5 µg/mL) por 24 horas y luego estimuladas con LPS (100 ng/mL) por 4 horas. Se evaluaron los niveles de expresión de citoquinas proinflamatorias (TNF-α, IL-6, IL-1ß, CCL2) y de la proteína antioxidante hemo oxigenasa 1 (HO-1), además de los niveles de activación de NF-κB. El tratamiento con 6 µg/mL de ARM resultó en un incremento en la viabilidad celular. El pretratamiento con ARM (1,5 - 4,5 µg/mL) fue efectivo para disminuir la expresión (TNF-α, IL-6 y CCL2) y secreción (TNF-α) de citoquinas proinflamatorias. Sin embargo, dosis altas de ARM incrementaron la activación de NF- κB y disminuyeron la expresión de HO-1 en células tratadas con LPS. Estos resultados sugieren un efecto antinflamatorio y un posible rol en el proceso antioxidante para dosis bajas de ARM en hepatocitos humanos frente al daño con LPS.

Rosa mosqueta (Rosa Rubiginosa) oil decreases inflammatory markers in human liver HepG2 cells treated with lipopolysaccharide. Gut microbiota alteration is one of the key factors affecting the onset and progression of hepatic steatosis by enhancing intestinal permeability and inducing an increase in circulating endotoxin lipopolysaccharide (LPS). LPS reaches the liver through the portal vein, where triggers inflammatory and pro-oxidant processes. On the other hand, essential oils-rich foods may have the capacity to abolish the deleterious effects of LPS in the liver. The objective of this study was to evaluate the effect of rosa mosqueta oil (ARM) in the prevention of inflammatory and oxidative processes in human hepatic cells HepG2 treated with LPS. HepG2 cells were exposed to different doses of ARM (1.5, 3, 4.5, 6 y 7.5 µg/mL) for 24 hours and then stimulated with LPS (100 ng/mL) for 4 hours. NF-κB activation, proinflammatory cytokines expression level (TNF-α, IL-6, IL-1ß, CCL2), and the antioxidant protein expression of hem oxygenase 1 (HO-1) were evaluated. Treatment with 6 µg/mL increased cellular viability. ARM pretreatment was effective in decreasing the expression (TNF-α, IL-6 y CCL2) and secretion (TNF-α) of proinflammatory cytokines. On the other hand, high doses of ARM increased NF-κB activation and decreased HO-1 expression in cells treated with LPS. These results may suggest an anti-inflammatory effect and a possible role in the antioxidant process in the case of the lower doses of ARM in human hepatic cells treated with LPS.

Bioatividade de compostos da pele de amendoim (Arachis hypogaea L. ): inibição enzimática, inibição do crescimento celular, estresse oxidativo e apoptose em células de câncer colorretal, HCT-116 / Bioactivity of peanut skin compounds (Arachis hypogaea L. ): enzyme inhibition, cell growth inhibition, oxidative stress and apoptosis in colorectal cancer cells, HCT-116

O câncer colorretal (CCR) é a segunda maior causa de morte por câncer no mundo. Os efeitos colaterais das terapias convencionais, normalmente agressivos, são comuns em todos os tratamentos indicados aos cânceres. O objetivo deste estudo foi avaliar os efeitos de fitoquímicos extraídos da pele de amendoim nos mecanismos antioxidantes e inibidores enzimáticos, e ainda, ação proliferativa e apoptótica em células de câncer colorretal - HCT116. O estudo incluiu dados teóricos publicados e resultados de analises in vitro, para estes foram testados extratos digeridos e não digeridos, sendo para a primeira etapa utilizados o extrato aquoso e de amostra digerida (fase 1 e fase 2), para a segunda etapa um extrato etanólico e etanólico digerido (fase 1 e fase 2): Manuscrito 1. "A review on the effects of bioactive compounds from peanut skin (Arachis hypogaea) on noncommunicable diseases". Manuscrito 2. "In Vitro Digestion of Peanut Skin Releases Bioactive Compounds and Increases Cancer Cell Toxicity. Manuscrito 3. "Controle de proliferação e apoptose via estresse oxidativo de extratos de pele de amendoim em células de câncer colorretal". A análise estatística dos dados laboratoriais foram comparados por meio de análise de variância (ANOVA) e teste de Tukey ou teste t, conforme apropriado. O nível de significância foi fixado em 0,05. As análises estatísticas foram realizadas utilizando SPSS 23.0 para Windows (IBM, Armonk, NY). Os principais resultados do estudo mostram que a pele de amendoim, subproduto da indústria de amendoim, é fonte de inúmeros compostos bioativos e podem ser liberados pelo processo digestivo simulado, sendo, portanto, considerados bioacessíveis. Os extratos da primeira etapa de digestão apresentaram efeitos antioxidantes, de inibição enzimática e citotóxico em células de câncer HCT116. Os extratos da segunda etapa da digestão apresentaram efeitos pró-apoptóticos via estresse oxidativo e mitocondrial. Em conclusão, os resultados apontaram potenciais aplicações do subproduto e seus compostos bioativos em benefício a saúde humana, assim como funções anticâncer em células HCT116 via de estresse oxidativo e modulação de NF-κB e IkB.

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Side effects from conventional, often aggressive, therapies are common in all cancer treatments. The objective of this study was to evaluate the effects of phytochemicals extracted from peanut skins on antioxidant and enzyme inhibitory mechanisms, as well as on proliferative and apoptotic action in colorectal cancer cells - HCT116. The study included published theoretical data and results of in vitro analyses, for which digested and undigested extracts can have tested for the first-stage aqueous extract, and digested sample was used (phase 1 and phase 2) for the second-stage ethanolic extract and digested ethanolic extract (phase 1 and phase 2): Manuscript 1. "A review on the effects of bioactive compounds from peanut skin (Arachis hypogaea) in non-communicable diseases". Manuscript 2. "In vitro digestion of peanut skin releases bioactive compounds and increases cancer cell toxicity. Manuscript 3. "Control of proliferation and apoptosis via oxidative stress of peanut skin extracts in colorectal cancer cells". Statistical analysis of laboratory data was compared using analysis of variance (ANOVA) and Tukey test or T-test, as appropriate. The significance level was set at 0.05. Statistical analyses were performed using SPSS 23.0 for Windows (IBM, Armonk, NY). The main results of the study show that the peanut skin, a by-product, is a source of numerous bioactive compounds, which can be released by the simulated digestive process, being bioaccessible. The extracts from the first stage showed antioxidant, enzyme inhibitory, and cytotoxic effects on HCT116 cells. The extracts from the second stage showed pro-apoptotic effects via oxidative and mitochondrial stress. In conclusion, the results point to potential applications of the by-product and its bioactive compounds to benefit human health, as well as anticancer functions in HCT116 cells via oxidative stress and modulation of NF-κB and IkB.