Ribose-cysteine and levodopa abrogate Parkinsonism via the regulation of neurochemical and redox activities in alpha-synuclein transgenic Drosophila melanogaster models.

Parkinson's disease (PD), the most prevalent type of parkinsonism, is a progressive neurodegenerative condition marked by several non-motor and motor symptoms. PD is thought to have a complex aetiology that includes a combination of age, genetic predisposition, and environmental factors. Increased expression of α-synuclein (α-Syn) protein is central to the evolvement of neuropathology in this devastating disorder, but the potential of ribose-cysteine and levodopa in abating pathophysiologic changes in PD model is unknown. Crosses were set up between flies conditionally expressing a pathological variant of human α-Syn (UAS-α-Syn) and those expressing GAL4 in neurons (elav-GAL4) to generate offspring referred to as PD flies. Flies were randomly assigned to five groups (n = 40) from the total population of flies, with each group having five replicates. Groups of PD flies were treated with either 500 mg/kg ribose-cysteine diet, 250 mg/kg levodopa diet, or a combination of the two compounds for 21 days, whereas the control group (w1118) and the PD group were exposed to a diet without ribose-cysteine or levodopa. In addition to various biochemical and neurochemical assays, longevity, larval motility, and gravitaxis assays were carried out. Locomotive capability, lifespan, fecundity, antioxidant state, and neurotransmitter systems were all significantly (p < 0.05) compromised by overexpression of α-Syn. However, flies treated both ribose cysteine and levodopa showed an overall marked improvement in motor functions, lifespan, fecundity, antioxidant status, and neurotransmitter system functions. In conclusion, ribose-cysteine and levodopa, both singly and in combination, potentiated a therapeutic effect on alpha-synuclein transgenic Drosophila melanogaster models of Parkinsonism.

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

Catechol-Modified and MnO2-Nanozyme-Reinforced Hydrogel with Improved Antioxidant and Antibacterial Capacity for Periodontitis Treatment.

Periodontitis is an inflammatory disease characterized by tooth loss and alveolar bone resorption. Bacteria are the original cause of periodontitis, and excess reactive oxygen species (ROS) encourage and intensify inflammation. In this study, a mussel-inspired and MnO2 NPs-reinforced adhesive hydrogel capable of alleviating periodontitis with improved antibacterial and antioxidant abilities was developed. The hydrogel was created by combining polyvinyl alcohol (PVA), 3,4-dihydroxy-d-phenylalanine (DOPA), and MnO2 nanoparticles (NPs) (named PDMO hydrogel). The hydrogel was demonstrated to be able to scavenge various free radicals (including total ROS─O2•- and OH•) and relieve the hypoxia in an inflammatory microenvironment by scavenging excess ROS and generating O2 due to its superoxide dismutase (SOD)/catalase (CAT)-like activity. Besides, under 808 nm near-infrared (NIR) light, the photothermal performance of the PDMO hydrogel displayed favorable antibacterial and antibiofilm effects toward Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis (up to nearly 100% antibacterial rate). Furthermore, the PDMO hydrogel exhibited favorable therapeutic efficacy in alleviating gingivitis in Sprague-Dawley rats, even comparable to or better than the commercial PERIO. In addition, in the periodontitis models, the PDMO2 group showed the height of the residual alveolar bone and the smallest shadow area of low density among other groups, indicating the positive role of the PDMO2 hydrogel in bone regeneration. Finally, the biosafety of the PDMO hydrogel was comprehensively investigated, and the hydrogel was demonstrated to have good biocompatibility. Therefore, the developed PDMO hydrogel provided an effective solution to resolve biofilm recolonization and oxidative stress in periodontitis and could be a superior candidate for local drug delivery system in the clinical management of periodontitis with great potential for future clinical translation.

Current Understanding of the Roles of Gut-Brain Axis in the Cognitive Deficits Caused by Perinatal Stress Exposure.

The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.

Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES.

BACKGROUND: The relationship between dietary total antioxidant capacity (DTAC) and death risk among CKD populations remains unclear. METHODS: Based on vitamin C equivalent antioxidant capacity (VCEAC) and the component dietary antioxidant index (CDAI) indices, we analyzed two cohorts to investigate the association of DTAC with all-cause and CVD mortality in CKD patients using data from National Health and Nutrition Examination Survey (2007-2018). VCEAC (n = 6330) and CDAI (n = 6300) cohorts with mortality follow-up data available through 2018 were included. Cox models with restricted cubic splines was used to model the nonlinear association between VCEAC/CDAI and outcomes in CKD patients. RESULTS: Our results showed L-shaped associations of DTAC with all-cause mortality among individuals with CKD stages 1-2 in both cohorts. Compared to the lowest quartile, higher dietary total antioxidant intake was associated with lower all-cause mortality risks among CKD stages 1-2 after adjustment for covariates, with HRs (95%CI) of 1.00, 0.91 (0.71,1.17), 0.69 (0.53,0.90), and 0.70 (0.54,0.91) in VCEAC, and similar respective estimate trends in CDAI. After sensitivity and subgroup analyses, there were no benefits for patients with stage 3-5 CKD or albuminuria. Mediation analysis revealed that the proportions mediated in both cohorts were less consistent. CONCLUSIONS: Moderate dietary total antioxidants intake has potential benefits for early-stage CKD patients. However, further evidence is needed to confirm whether patients with worsening CKD can benefit in the long term.

Morphological and Functional Analysis of Cardiac Ameliorations in Elderly Rats Supplemented with a Magnolol Extract Complex / Análisis Morfológico y Funcional de las Mejoras Cardíacas en Ratas Ancianas Suplementadas con un Complejo de Extracto de Magnolol

SUMMARY: Magnolia bark extract supplementation has an anti-oxidative role in mammalians. However, its role in physiological aged-associated heart insufficiency is not known yet. Therefore, we investigated the effects of a magnolia bark complex, including magnolol and honokiol components (MAHOC), in elderly rat hearts (24-month-old aged group). One group of aged rats was supplemented with MAHOC (400 mg/kg/d, for 12 weeks) besides the standard rat diet while the second group of elderly rats and adult rats (to 6-month- old adult-group) were only fed with the standard rat diet. The morphological analysis using light microscopy has shown marked myofibrillar losses, densely localized fibroblasts, vacuolizations, infiltrated cell accumulations, and collagen fibers in the myocardium of the elderly rats compared to the adults. We also detected a markedly increased amount of degenerated cardiomyocytes including the euchromatic nucleus. The MAHOC supplementation of the elderly rats provided marked ameliorations in these abnormal morphological changes in the heart tissue. Furthermore, electrophysiological analysis of electrocardiograms (ECGs) in the supplemented group showed significant attenuations in the prolonged durations of P-waves, QRS-complexes, QT-intervals, and low heart rates compared to the unsupplemented elderly group. The biochemical analysis also showed significant attenuations in the activity of arylesterase and total antioxidant status in the myocardium of the supplemented group. We further determined significant attenuations in the activity of a mitochondrial enzyme succinate dehydrogenase, known as a source of reactive oxygen species (ROS), and the decreased level of ATP/ADP in the heart homogenates of the supplemented group. Moreover, under in vitro conditions by using an aging-mimicked cardiac cell line induced by D-galactose, we demonstrated that MAHOC treatment could provide prevention of depolarization in mitochondria membrane potential and high-level ROS production. Overall, our data presented significant myocardial ameliorations in physiological aging-associated morphological alterations parallel to the function and biochemical attenuations with MAHOC supplementation, at most, through recoveries in mitochondria.

La suplementación con extracto de corteza de magnolia tiene un papel antioxidante en los mamíferos, sin embargo, su rol en la insuficiencia cardíaca asociada al envejecimiento fisiológico aún no se conoce. Por lo anterior, investigamos los efectos de un complejo de corteza de magnolia, incluidos los componentes magnolol y honokiol (MAHOC), en corazones de ratas seniles (grupo de edad de 24 meses). La alimentación de grupo de ratas seniles se complementó con MAHOC (400 mg/kg/d, durante 12 semanas) además de la dieta estándar, mientras que el segundo grupo de ratas seniles y ratas adultas (hasta el grupo de adultos de 6 meses) solo recibió la dieta estándar para ratas. El análisis morfológico mediante microscopía óptica ha mostrado marcadas pérdidas miofibrilares, fibroblastos densamente localizados, vacuolizaciones, acumulaciones de células infiltradas y fibras de colágeno en el miocardio de las ratas seniles en comparación con las adultas. También detectamos una cantidad notablemente mayor de cardiomiocitos degradados, incluido el núcleo eucromático. La suplementación con MAHOC de las ratas seniles proporcionó mejoras marcadas en estos cambios morfológicos anormales en el tejido cardiaco. Por otra parte, el análisis de los electrocardiogramas (ECG) en el grupo suplementado mostró atenuaciones significativas en las duraciones prolongadas de las ondas P, los complejos QRS, los intervalos QT y las frecuencias cardíacas bajas, en comparación con el grupo de ratas seniles sin suplementación alimenticia. El análisis bioquímico también mostró atenuaciones significativas en la actividad de la arilesterasa y el estado antioxidante total en el miocardio del grupo suplementado. Determinamos además atenuaciones significativas en la actividad de la enzima mitocondrial succinato deshidrogenasa, conocida como fuente de especies reactivas de oxígeno (ROS), y la disminución del nivel de ATP/ADP en los homogeneizados de corazón del grupo suplementado. Además, en condiciones in vitro mediante el uso de una línea de células cardíacas, imitando el envejecimiento inducido por D- galactosa, demostramos que el tratamiento con MAHOC podría prevenir la despolarización en el potencial de membrana de las mitocondrias y la producción de ROS de alto nivel. En general, nuestros datos presentaron mejoras miocárdicas significativas en alteraciones morfológicas asociadas con el envejecimiento fisiológico paralelas a la función y atenuaciones bioquímicas con la suplementación con MAHOC, como máximo, a través de recuperaciones en las mitocondrias.

Astaxanthin ameliorates spinal cord edema and astrocyte activation via suppression of HMGB1/TLR4/NF-κB signaling pathway in a rat model of spinal cord injury.

Spinal cord edema is a quick-onset phenomenon with long-term effects. This complication is associated with inflammatory responses, as well as poor motor function. No effective treatment has been developed against spinal edema, which urges the need to provide novel therapies. Astaxanthin (AST) is a fat-soluble carotenoid with anti-inflammatory effects and a promising candidate for treating neurological disorders. This study aimed to investigate the underlying mechanism of AST on the inhibition of spinal cord edema, astrocyte activation, and reduction of inflammatory responsesin a rat compression spinal cord injury (SCI) model. Male rats underwent laminectomy at thoracic 8-9, and the SCI model was induced using an aneurysm clip. After SCI, rats received dimethyl sulfoxide or AST via intrathecal injection. The effects of AST were examined on the motor function, spinal cord edema, integrity of blood-spinal cord barrier (BSCB), and expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4), and matrix metallopeptidase- 9 (MMP-9) post-SCI. We showed that AST potentially improved the recovery of motor function and inhibited the spinal cord edema via maintaining the integrity of BSCB, reducing the expression of HMGB1, TLR4, and NF-κB, MMP-9 as well as downregulation of astrocyte activation (GFAP) and AQP4 expression. AST improves motor function and reduces edema and inflammatory responses in the spinal tissue. These effects are mediated by suppression of the HMGB1/TLR4/NF-κB signaling pathway, suppressing post-SCI astrocyte activation, and decreasing AQP4 and MMP-9 expression.

Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura / Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos, presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: Reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin. (AU)

[Translated article] Oral Supplementation and Systemic Drugs for Skin Aging: A Narrative Review / Tratamiento mediante suplementación oral o fármacos sistémicos del envejecimiento cutáneo. Revisión narrativa de la literatura

Skin aging is influenced by intrinsic and extrinsic factors and involves multiple pathogenic mechanisms. The most widely used treatments are topical products and minimally invasive procedures. Evidence on the benefits of systemic therapy is limited for several reasons: reliance on mostly small and predominantly female samples, short study durations, methodologic heterogeneity, and a lack of consensus on which outcome measures are clinically relevant. Furthermore, systemic drugs and oral supplements are not without adverse effects. Oral hydrolyzed collagen and oral hyaluronic acid are well tolerated, and numerous clinical trials show they can mitigate some signs of skin aging. Low-dose oral isotretinoin is another option, but it has a higher risk of adverse effects. Evidence is lacking on the effects of the many dietary supplements on offer, such as vitamins, flavonoids, plant extracts, and trace elements. The future of skin aging management would appear to lie in the use of senolytic and senomorphic agents targeting senescent cells in the skin. (AU)

El envejecimiento cutáneo está influido por factores intrínsecos y extrínsecos y múltiples mecanismos patogénicos están involucrados. Los tratamientos utilizados en la actualidad son sobre todo tópicos o son procedimientos mínimamente invasivos. La evidencia sobre la utilidad de la terapia sistémica es limitada: los estudios son en su mayoría de pequeño tamaño, de reducida duración, incluyen a mujeres de manera mayoritaria, la metodología de evaluación es heterogénea y no hay parámetros consensuados de respuesta clínica relevante. Además, los suplementos o fármacos sistémicos no están exentos de efectos adversos. El colágeno hidrolizado oral y el ácido hialurónico oral son bien tolerados y múltiples ensayos clínicos muestran que pueden mitigar algunos signos de envejecimiento cutáneo. La isotretinoína oral en dosis bajas es otra alternativa, pero con un mayor potencial de efectos adversos. Múltiples suplementos, como vitaminas, flavonoides, diversos extractos de plantas y oligoelementos presentan escasa evidencia clínica. El futuro del manejo del envejecimiento cutáneo parece ser el tratamiento con agentes senolíticos o senomórficos dirigidos específicamente contra células cutáneas senescentes. (AU)

Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Alginate Beads Containing Cerium-Doped Mesoporous Glass and Curcumin: Delivery and Stabilization of Therapeutics.

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica. In this work, various systems have been synthesized: starting from mesoporous silica glasses (MGs), cerium-containing MGs have been produced; then, these systems have been loaded with 4 to 6% of curcumin. Finally, various MGs at different compositions have been included in alginate beads. In vitro studies showed that these hybrid materials enable the stabilization and effective delivery of curcumin and that a synergic effect can be achieved if Ce3+/Ce4+ and curcumin are both part of the beads. From swelling tests, it is possible to confirm a controlled curcumin release compartmentalized into the gastrointestinal tract. For all beads obtained, a curcumin release sufficient to achieve the antioxidant threshold has been reached, and a synergic effect of cerium and curcumin is observed. Moreover, from catalase mimetic activity tests, we confirm the well-known catalytic activity of the couple Ce3+/Ce4+. In addition, an extremely good radical scavenging effect of curcumin has been demonstrated. In conclusion, these systems, able to promote an enzymatic-like activity, can be used as drug delivery systems for curcumin-targeted dosing.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Evaluation of antioxidant, photoprotective and antinociceptive activities of Marcetia macrophylla extract: potential for formulation of sunscreens / Avaliação da atividade antioxidante, photoprotetora e antinociceptiva de Marcetia macrophylla: potencial formulação fotoprotetora

The antioxidant, photoprotective and antinociceptive Marcetia macrophylla active extract was investigated as an active ingredient in a sunscreen cream formulation. Thus, the M. macrophylla extract showed IC50 of 3.43 mg/ml of the antioxidant (DPPH∙ scavenging test) and Sun Protection Factor of 20.25 (SPF/UV-B, at 250 µg/ml) and UV-A of 78.09% (photobleaching trans-resveratrol test). The antinociceptive activity was superior to all standards tested using the in vivo acetic acid-induced writhing test (99.14% at the dose of 200 mg/kg) and the high-performance liquid chromatography coupled with diode array detector and mass spectroscopy multi-stage (HPLC-DAD-MS/MS) enabled the structural characterization of the quercetin-3-O-hexoside, quercetin-3-O-pentoside and quercetin-3-O-desoxihexoside. The pharmaceutical formulation containing the Marcetia macrophylla crude active extract was prepared and the physicochemical tests (organoleptic characteristics, pH analysis and centrifugation), the in vitro UVB (sun protection factor, SPF) and UVA (β-carotene) using the spectroscopic method were investigated. The formulation showed satisfactory results concerning the physicochemical parameters evaluated and active against the UV test. Thus, M. macrophylla showed biological activities with potential use in pharmaceutical preparations.

O extrato bruto de Marcetia macrophylla mostrou atividade antioxidante, fotoprotetora e antinociceptiva, sendo em seguida investigado como ingrediente ativo em uma formulação fotoprotetora. Assim, o extrato de M. macrophylla apresentou atividade antioxidante com IC50 de 3,43 mg/mL (teste de sequestro do DPPH∙) e Fator de Proteção Solar de 20,25 (FPS/UV-B, 250 µg/mL) e UV-A de 78,09% (teste de fotobranqueamento do trans-resveratrol). A atividade antinociceptiva usando o teste in vivo de contorções abdominais induzidas por ácido acético foi superior a todos os padrões testados (99,14% na dose de 200 mg/Kg). A análise por cromatografia líquida de alta eficiência acoplada a detector de fotodiodos e espectroscopia de massas multi-estágio (CLAE-DAD-EM/EM) possibilitou a caracterização dos flavonoides quercetina-3-O-hexosídeo, quercetina-3-O-pentosídeo e quercetina-3-O-desoxihexosídeo. A formulação farmacêutica contendo o extrato ativo bruto de Marcetia macrophylla foi preparada e os testes físico-químicos (características organolépticas, análise de pH e centrifugação), o UVB in vitro (fator de proteção solar, FPS) e UVA (β-caroteno) foram investigados. A formulação apresentou resultados satisfatórios frente aos parâmetros físico-químicos avaliados e ativos contra UV. Assim, M. macrophylla apresentou atividades biológicas com potencial uso em preparações fitofarmacêuticas.

Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Use of bacaba peel for the development of hydroelectrolytic beverages and their consumer acceptance

Abstract The hydroelectrolytic beverages segment has been expading its market and introducing new flavors in order to meet the demand for new products. However, experimental studies find concerns about the chemical compositions of these drinks. The aim of this study was to develop a drink without synthetic coloring or flavoring, with functional attributes based on the bacaba (Oenocarpus bacaba Mart.) peel extract. Two hydroelectrolytic drinks were developed, one hypotonic and the other isotonic, containing 0.5 and 1.0% of bacaba peel extract. Physicochemical characterization, determination of total phenolic compounds, anthocyanins, and antioxidant capacity were perfomed, in addition to color evaluation, as well as sensory analysis by means of preference tests. The developed formulations showed potential antioxidant activity and natural red coloring due to the phenolic compounds and anthocyanins present in the beverages. The sensory evaluation indicated positive acceptance by the tasters regarding the addition of the bacaba peel extract to the beverage formulations. The developed formulations demonstrated that the use of the bacaba peel is a viable option for the production of sports drinks, acting as a natural dye and offering health benefits due to its bioactive compounds.

Potential inhibitory effects of low-dose thoron inhalation and ascorbic acid administration on alcohol-induced hepatopathy in mice.

Although thoron inhalation exerts antioxidative effects in several organs, there are no reports on whether it inhibits oxidative stress-induced damage. In this study, we examined the combined effects of thoron inhalation and ascorbic acid (AA) administration on alcohol-induced liver damage. Mice were subjected to thoron inhalation at 500 or 2000 Bq/m3 and were administered 50% ethanol (alcohol) and 300 mg/kg AA. Results showed that although alcohol administration increased the levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) in the serum, the combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration effectively inhibited alcohol-induced liver damage. The combination of thoron inhalation (500 Bq/m3) and AA administration 24 h after alcohol administration increased catalase (CAT) activity. Alcohol administration significantly decreased glutathione (GSH) levels in the liver. The GSH content in the liver after 2000 Bq/m3 thoron inhalation was lower than that after 500 Bq/m3 thoron inhalation. These findings suggest that the combination of thoron inhalation at 500 Bq/m3 and AA administration has positive effects on the recovery from alcohol-induced liver damage. The results also suggested that thoron inhalation at 500 Bq/m3 was more effective than that at 2000 Bq/m3, possibly because of the decrease in GSH content in the liver. In conclusion, the combination of thoron inhalation at 500 Bq/m3 and AA administration promoted an early recovery from alcohol-induced liver damage.

Interplay between fatty acid desaturase2 (FADS2) rs174583 genetic variant and dietary antioxidant capacity: cardio-metabolic risk factors in obese individuals.

OBJECTIVE: Polymorphisms of the fatty acid desaturase (FADS) gene cluster have been associated with obesity and its-related consequences. This cross-sectional study aimed to investigate whether the adherence to dietary non-enzymatic antioxidant capacity (NEAC), reflecting the antioxidant potential of the whole diet, modifies the association of FADS2 rs174583 polymorphism with cardio-metabolic risk factors in obese adults. METHODS: The present study included 347 healthy obese adults (aged 20-50 years). Dietary NEAC was assessed by a validated food frequency questionnaire with 147 items and estimated through total radical-trapping antioxidant parameters (TRAP), oxygen radical absorbance capacity (ORAC), and ferric reducing ability of plasma (FRAP) with the use of published databases. FADS2 rs174583 polymorphism was characterized using PCR-RFLP. ANCOVA multivariate interaction model was used to analyze gene-diet interactions. RESULTS: after adjustment for the confounding variables (age, physical activity, SES and WC), this study showed significant interactions between rs174583 polymorphism and adherence to dietary ORAC on the serum cholesterol (P Interaction = 0.029), LDL-C (P Interaction = 0.025) and HDL-C levels (P Interaction = 0.049) among the male group; minor allele carriers who had the highest adherence to the NEAC (ORAC) showed a better metabolic profile (lower TG and LDL-C and higher HDL-C) (P < 0.05). Among women, the dietary ORAC-rs174583 interactions were statistically significant for the serum insulin concentration (P Interaction = 0.020), QUICKI (P Interaction = 0.023) and HOMA-IR (P Interaction = 0.017); the highest QUICKI and the lowest HOMA-IR and serum insulin levels were observed in the CC homozygote carriers with the moderate compliance with the dietary ORAC (P < 0.05). In addition, the dietary TRAP modified the association between FADS2 variant and change in LDL-C levels (P Interaction = 0.037); the homozygous wild-type (CC) women who placed in the top tertile of TRAP had significantly the lowest LDL-C levels than those in the second tertile (P < 0.05). CONCLUSION: These data indicate that the FADS2 rs174583 polymorphism interacts with the dietary NEAC to influence cardio-metabolic risk factors in obese subjects. Replication in prospective cohort studies among other populations is required to confirm the results of our study.

High-intensity resistance exercise and Schinus terenbinthifolius supplementation attenuate oxidative stress and muscle damage biomarkers / El ejercicio de resistencia de alta intensidad y la suplementación con Schinus terenbinthifolius atenúan los biomarcadores del estrés oxidativo y daño muscular

SUMMARY: High-intensity physical exercises can cause oxidative stress and muscle damage. Several medicinal plants have been used as antioxidant and anti-inflammatory agents. The present study evaluated high-intensity resistance exercise (HIRE) associated with Schinus Terebentifholius ethanolic extract (EE) on oxidative parameters and muscle damage in Wistar rats. Animals were divided into 04 groups (n=10/group): 1. Control (CG) - animals that did not undergo HIRE and were treated with vehicle (distilled water, orally); 2. Acute exercise (AE) - animals submitted to acute exercise session; 3. Exercise + vehicle (EV) - animals that underwent HIRE and were treated with vehicle and 4. Exercise + extract (EX) animals administered with Schinus terebenthifolius EE (100mg/Kg, orally) and submitted to the exercise session. Schinus terebenthifolius EE showed high in vitro antioxidant activity (13.88 ± 0.36 mg/mL). Before the experimental period, lactate was measured at pre and post moments of AE (p<0.0001) and EX (p<0.0001) groups. After the acute session, the following were evaluated: oxidative stress {malondialdehyde (MDA), sulfhydryl groups (SH) and ferric reducing antioxidant power (FRAP)}, muscle damage (creatine kinase (CK) and lactate dehydrogenase (LDH)), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the in vivo analyses of the EX group compared to AE and EV groups, respectively: hepatic (MDA: p<0.0001 and SH: p=0.0033, in both; FRAP: p=0.0011 and p=0.0047), muscle (MDA, SH and FRAP: p<0.0001, in both; CK: p=0.0001 and p<0.0001; LDH: p<0.0001, in both), serum levels (MDA: p=0.0003, p=0.0012, SH: p=0.0056, p=0.0200, FRAP: p=0.0017 and p=0.0165) were significant. There was no significant difference in ALT and AST markers. It could be concluded that Schinus terebenthifolius EE associated with HIRE attenuated oxidative stress and muscle damage in rats.

RESUMEN: Los ejercicios físicos de alta intensidad pueden causar estrés oxidativo y daño muscular. Varias plantas medicinales se han utilizado como agentes antioxidantes y antiinflamatorios. El presente estudio evaluó el ejercicio de resistencia de alta intensidad (HIRE) asociado con el extracto etanólico (EE) de Schinus terebentifholius sobre los parámetros oxidativos y el daño muscular en ratas Wistar. Los animales se dividieron en 4 grupos (n=10/grupo): 1. Control (GC) - animales que no se sometieron a HIRE y fueron tratados con vehículo (agua destilada, por vía oral); 2. Ejercicio agudo (AE) - animales sometidos a sesión de ejercicio agudo; 3. Ejercicio + vehículo (EV) - animales que se sometieron a HIRE y fueron tratados con vehículo y 4. Ejercicio + extracto (EX) animales administrados con Schinus terebenthifolius EE (100 mg/kg, por vía oral) y sometidos a la sesión de ejercicio. Schinus terebenthifolius EE mostró una alta actividad antioxidante in vitro (13,88 ± 0,36 mg/mL). Antes del período experimental, se midió el lactato en los momentos pre y post de los grupos AE (p<0,0001) y EX (p<0,0001). Tras la sesión aguda, se evaluaron: el estrés oxidativo malondialdehído (MDA), grupos sulfhidrilo (SH) y poder antioxidante reductor férrico (FRAP), daño muscular (creatina quinasa (CK) y lactato deshidrogenasa (LDH)), alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). En los análisis in vivo del grupo EX frente a los grupos AE y EV, respectivamente: hepático (MDA: p<0,0001 y SH: p=0,0033, en ambos; FRAP: p=0,0011 y p=0,0047), muscular (MDA, SH y FRAP: p<0,0001, en ambos; CK: p=0,0001 y p<0,0001; LDH: p<0,0001, en ambos), niveles séricos (MDA: p=0,0003, p=0,0012, SH: p=0,0056, p=0,0200, FRAP: p=0,0017 y p=0,0165) fueron significativas. No hubo diferencia significativa en los marcadores ALT y AST. Se podría concluir que Schinus terebenthifolius EE asociado con HIRE atenuó el estrés oxidativo y el daño muscular en ratas.

Anti-diabetic efficacy of combination treatment with the nitric oxide metabolite nitrite and the endogenous antioxidant glutathione in diabetic mice: glutathione combination does not hamper the anti-diabetic effect of nitrite.

OBJECTIVE: The nitric oxide (NO) metabolite nitrite has been shown to attenuate hyperglycemia via its increase in insulin sensitivity and glucose uptake. However, the oral use of nitrite is limited due to its potential formation of the carcinogenic N-nitrosamines via reaction of acidic nitrite and the secondary amines. We investigated the anti-diabetic effect of sodium nitrite (SN) combined with glutathione (GSH) in streptozotocin (STZ)-induced diabetic mice for potential use of GSH as a protective agent in future nitrite therapy. MATERIALS AND METHODS: STZ-induced diabetic mice were orally treated for 5 weeks with vehicle, SN, GSH or SN + GSH. Oral glucose tolerance test and the measurement of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were carried out to evaluate anti-diabetic effects of SN and SN + GSH. Plasma levels of total NO metabolites (NOx) were measured to confirm nitrite absorption. RESULTS: SN and SN + GSH significantly improved the glucose tolerance (p < 0.05), but GSH alone did not. The efficacy of combination treatment with SN and GSH in improving the glucose tolerance was higher than that of SN alone. Oral treatment with SN or SN + GSH significant reduced FBG and HbA1c levels (p < 0.05). Interestingly, daily oral administration of SN + GSH was more effective in reducing FBG and HbA1c levels than that of SN alone. Administration of SN or SN + GSH significantly increased plasma NOx levels (p < 0.05), and combination treatment with SN + GSH was more effective in increasing plasma NOx levels than that with SN alone. CONCLUSIONS: Combination treatment with SN and GSH is more effective in controlling hyperglycemia and increasing the plasma NOx levels in an experimental mouse model of diabetes. Since oral administration of GSH has been shown to be non-toxic in humans, the combination of SN and GSH may be important in potential future nitrite therapy.

The effect of acute intradermal administration of ascorbate on heat loss responses in older adults with uncomplicated controlled hypertension.

NEW FINDINGS: What is the central question of this study? Does acute intradermal administration of the antioxidant ascorbate augment local forearm cutaneous vasodilatation and sweating via nitric oxide synthase (NOS)-dependent mechanisms during exercise-heat stress in older adults with uncomplicated controlled hypertension? What is the main finding and its importance? Relative to the control site, ascorbate had no effect on forearm cutaneous vascular conductance (CVC) and sweat rate, although CVC was reduced with NOS inhibition in older adults with hypertension. Acute local administration of ascorbate to forearm skin does not modulate heat loss responses during exercise-heat stress in older adults with hypertension. ABSTRACT: Nitric oxide synthase (NOS) contributes to the heat loss responses of cutaneous vasodilatation and sweating during exercise. However, the contribution of NOS may be attenuated in individuals with uncomplicated, controlled hypertension due to elevated oxidative stress, which can reduce NO bioavailability. We evaluated the hypothesis that the acute local intradermal administration of the antioxidant ascorbate would enhance cutaneous vasodilatation and sweating via NOS-dependent mechanisms during an exercise-heat stress in adults with hypertension. Habitually active adults who were normotensive (n = 14, 7 females, 62 ± 4 years) or had uncomplicated, controlled hypertension (n = 13, 6 females, 62 ± 5 years) performed 30 min of moderate-intensity (50% of their pre-determined peak oxygen uptake) semi-recumbent cycling in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and sweat rate were assessed at four forearm skin sites continuously perfused with (1) lactated Ringer solution (Control), (2) 10 mM antioxidant ascorbate, (3) 10 mM NG -nitro-l-arginine methyl ester (l-NAME), a non-selective NOS inhibitor, or (4) a combination of ascorbate and l-NAME. Relative to Control, no effect of ascorbate was observed on CVC or sweating in either group (P = 0.619). However, l-NAME reduced CVC relative to Control in both groups (P ≤ 0.038). No effect of any treatment on sweating was observed (P ≥ 0.306). Thus, acute local administration of ascorbate to forearm skin does not enhance the activation of heat loss responses of cutaneous vasodilatation and sweating in older adults, and those with hypertension during an exercise-heat stress.