Gut Microbiota Modulation by Bioactive Compounds from Ilex paraguariensis: an In Vivo Study.

Yerba-mate (Ilex paraguariensis) is recognized for its biocompounds and bioactive properties. This study aimed to assess the potential of yerba-mate extract to modulate the intestinal microbiota in rats. After the ethical committee approval (CEUA - UPF, number 025/2018), the Wistar rats were given a daily dose of 3.29 mg of phenolic compounds per animal for 45 days. The antioxidant activity of the extract was assessed by ABTS and FRAP assays and the total phenolic compounds was measured at different pH levels. Identification and quantification of chlorogenic acid isomers were carried out using high-performance liquid chromatography (HPLC). Intestinal microbiota modulation was evaluated by administering the yerba-mate extract or water (control) to Wistar rats via intragastric gavage and its efficiency was measured through PCR. The antioxidant capacity of the yerba-mate extract was 64.53 ± 0.26 µmol Trolox/mL (ABTS) and 52.96 ± 0.86 µmol Trolox/mL (FRAP). The total phenolic compounds showed higher levels at pH 7.5 compared to pH 2.0. Chlorogenic acid isomers were found in greater abundance, with a concentration of 14.22 g/100 g. The administration of the extract resulted in positive modulation of the intestinal microbiota, specifically for the genera Lactobacillus sp. and Prevotella sp. The increase of these genera is related to the promotion of homeostasis of the gut microbiota. Therefore, these findings indicate that yerba-mate extract possesses significant antioxidant activity and can effectively modulate the intestinal microbiota in rats. These results support the potential use of yerba-mate as an alternative for controlling and preventing diseases associated with intestinal dysbiosis.

Analysis of correlation of glucose dosage by glycosimeter, laboratory dosage and artificial intelligence equipment / Correlação da dosagem de glicose por glicosímetro, dosagem laboratorial e de equipamento de inteligência artificial

ABSTRACT Introduction With the increasing number of cases related to Diabetes Mellitus (DM), glycemic control through laboratory methods or rapid tests is essential. Objective To analyze the correlation of three glucose determination methodologies (Glucometer, laboratory analysis and with point of care artificial intelligence equipment). Method Blood samples from the digital pulp and venous blood from the antecubital fossa were collected from 20 volunteers of different ages and sex. Blood glucose measurements were determined by the 3 methodologies mentioned above. Result Spearmans correlation analysis carried out between all types of tests shows that there is a strong and statistically significant positive correlation, indicating the compatibility of results regardless of the method applied. Conclusion The methodologies are correlated, however, the average values?? obtained by artificial intelligence were 40% higher, which can impact the clinical interpretation of results.

RESUMO Introdução Com o número crescente de casos relacionados a Diabetes Mellitus (DM), é indispensável o controle glicêmico através de métodos laboratoriais ou testes rápidos. Objetivo Analisar a correlação de três metodologias de determinação de glicose (Glicosímetro, análise laboratorial e com o equipamento com inteligência artificial de point of care). Método Foram coletadas amostras de sangue da polpa digital e sangue venoso da fossa antecubital de 20 voluntários de diferentes idades e sexo. Dosagens de glicose sanguínea foram determinadas pelas 3 metodologias acima citadas. Resultado A análise de correlação de Spearman realizada entre todos os tipos de testes mostra que há uma correlação positiva forte e estatisticamente significante, indicando a compatibilidade de resultados independentemente do método aplicado. Conclusão As metodologias apresentam correlação, no entanto, os valores médios obtidos pela inteligência artificial mostraram-se 40% mais elevada que pode impactar na interpretação clínica dos resultados.

Diclofenac Administration after Physical Training Blunts Adaptations of Peripheral Systems and Leads to Losses in Exercise Performance: In Vivo and In Silico Analyses.

Recovery in athletes is hampered by soreness and fatigue. Consequently, nonsteroidal anti-inflammatory drugs are used as an effective strategy to maintain high performance. However, impact of these drugs on adaptations induced by training remains unknown. This study assessed the effects of diclofenac administration (10 mg/kg/day) on rats subjected to an exhaustive test, after six weeks of swimming training. Over the course of 10 days, three repeated swimming bouts were performed, and diclofenac or saline were administered once a day. Trained animals exhibited higher muscle citrate synthase and lower plasma creatinine kinase activities as compared to sedentary animals, wherein diclofenac had no impact. Training increased time to exhaustion, however, diclofenac blunted this effect. It also impaired the increase in plasma and liver interleukin-6 levels. The trained group exhibited augmented catalase, glutathione peroxidase, and glutathione reductase activities, and a higher ratio of reduced-to-oxidized glutathione in the liver. However, diclofenac treatment blunted all these effects. Systems biology analysis revealed a close relationship between diclofenac and liver catalase. These results confirmed that regular exercise induces inflammation and oxidative stress, which are crucial for tissue adaptations. Altogether, diclofenac treatment might be helpful in preventing pain and inflammation, but its use severely affects performance and tissue adaptation.

Soybean Plant Metabolism under Water Deficit and Xenobiotic and Antioxidant Agent Application.

The aim was to evaluate the interactive effects on biochemistry and physiology of soybean plants exposed to simultaneous xenobiotic and water deficit stresses, and the possible attenuation of plant damage by an antioxidant agent. Soybean plants were submitted to eight different soil water potentials, in two experiments (first experiment: -0.96, -0.38, -0.07, -0.02 MPa, and second experiment: -3.09, -1.38, -0.69, -0.14 MPa), xenobiotic, and antioxidant agent applications. Was observed a reduction in water status, gas exchange, photosynthetic pigments, photosystem II quantum yield, and increased leaf temperature in plants under low water availability. Water deficit also induced oxidative stress by the increased production of reactive oxygen species, cellular and molecular damage, and induction of the antioxidant defense metabolism, reduction of gas exchange, water status, and photosynthetic efficiency. The xenobiotic application also caused changes, with deleterious effects more pronounced in low soil water availability, mainly the reactive oxygen species production, consequently the antioxidant activity, and the oxidative damages. This indicates different responses to the combination of stresses. Antioxidant enzyme activity was reduced by the application of the antioxidant agent. Principal Component Analysis showed a relation with the antioxidant agent and reactive oxygen species, which is probably due to signaling function, and with defense antioxidant system, mainly glutathione, represented by thiols.

In Vitro Biological Properties of Solanum sessiliflorum (Dunal), an Amazonian Fruit.

Solanum sessiliflorum is an Amazonian fruit (cubiu) that has been domesticated since pre-Colombian era. It is also used in folk medicine to treat some clinical conditions. This investigation chemically characterized and analyzed the in vitro antioxidant and antitumoral effect of a cubiu pulp/seed hydroalcoholic extract. Cubiu extract was chemically characterized by high-performance liquid chromatography with diode array detector (HPLC-DAD), its antioxidant capacity measured by 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the following complementary in vitro protocols were performed: (1) cytoprotective effect of cubiu on human peripheral blood mononuclear cells (PBMCs) exposed to H2O2, a genotoxic and procarcinogen molecule; (2) effect of cubiu on low density lipoproteins oxidation; and (3) cytotoxic and antiproliferative effect on breast (MCF-7) and colorectal (HT-29) cancer cell lines. Biochemical and flow cytometry analyses were conducted in these protocols. Cubiu extract presented high concentrations of caffeic and gallic acids, beta-carotene, catechin, quercetin, and rutin, and its antioxidant capacity was confirmed. Cubiu attenuated H2O2 cytotoxicity on PBMCs, presented lowering effect on LDL oxidation, and induced mortality and proliferative inhibition of colorectal cancer cells. In cancer cells, cubiu extract at 10 µg/mL showed similar effects to 5-fluorouracil chemo drug reducing its viability and frequency of S-phase, indicating that cells are undergoing mitosis. In summary, despite the limitations of in vitro protocols, our results suggest that cubiu has several biological properties that affect human health.

Acetaminophen Oxidation and Inflammatory Markers - A Review of Hepatic Molecular Mechanisms and Preclinical Studies.

Acetaminophen is a widely used analgesic for pain management, especially useful in chronic diseases, such as rheumatoid arthritis. However, easy access to this medicine has increased the occurrence of episodes of poisoning. Patients often develop severe liver damage, which may quickly lead to death. Consequently, numerous studies have been conducted to identify new biomarkers that allow the prediction of the degree of acetaminophen intoxication and thus intervene in a timely manner to save patients' lives. This review highlights the main mechanisms of the induction and progression of liver damage arising from acetaminophen poisoning. In addition, we have discussed the possibility of using new clinical biomarkers for detecting acetaminophen poisoning.

Multiple mechanistic action of Rosmarinus officinalis L. extract against ethanol effects in an acute model of intestinal damage.

The high levels of oxidative stress and inflammation can be present in the etiology of degenerative intestinal pathologies associated with ethanol ingestion. The Rosmarinus officinalis L. has exhibited several physiological and medicinal activities. In this investigation, we intended to clarify, for the first time, the antioxidant and anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. (eeRo) against an acute damage induced by ethanol, specifically in the small intestine of rats. The rats were treated three times, at every 24 h, with eeRo at 500-1000 mg/kg or vehicle, oral gavage. All groups got a single dose of ethanol (2 ml/kg), oral gavage, after 36 h of fasting and 1 h after the last dose of eeRo or vehicle administration. We performed the mensuration of oxidative stress profile in lipid peroxidation in serum and intestine; Na+/K+ ATPase, catalase, and superoxide dismutase activities assays only in intestine; and anti-inflammatory evidences of eeRo in myeloperoxidase activity assay only in the intestine. The eeRo was able to protect the animals against the lipid peroxidation in serum and intestine. It prevented the reduction in Na+/K+ ATPase and catalase levels induced by ethanol in the intestine. In addition, eeRo increased the superoxide dismutase activity when compared to control and protected the intestine against elevations in myeloperoxidase activity caused by ethanol. Our results suggested that eeRo exerted a significant intestinal protective effect by antioxidant and anti-inflammatory mechanisms. Thus, the eeRo represented a promising agent against intestinal lesions induced by ethanol.

Functional and biochemical adaptations of elite level futsal players from Brazil along a training season.

BACKGROUND AND OBJECTIVE: Although hard training is mandatory in elite level futsal training, few studies have proposed a biochemical follow up in futsal players during a whole season. Therefore, the aim of this study was to compare functional and biochemical markers in Brazilian elite level futsal players throughout a competition season. MATERIALS AND METHODS: Eight players aged 25.5±5.4 years were evaluated at three time points: preseason (T1), immediately before the FIFA®-Intercontinental-Futsal-Cup (T2), and at the end of the season (T3), with a tapering period of 1 week before T2. Functional parameters (weight, height, body fat, VO2max, heart rate, and distance ran) and blood sampling for cell count and lipid profile (cholesterol, HDL-C, LDL-C, triglycerides) were assessed at each time point. After, a Yo-Yo R2 test was carried out in each time point (T1, T2 and T3) and blood samples to assess skeletal muscle damage (creatine kinase [CK], lactate dehydrogenase [LDH]), inflammation (C-reactive protein [CRP]) and oxidative stress markers (ischemia modified albumin [IMA], and advanced oxidation protein products [AOPP]) were obtained before and after the tests. RESULTS: Although functional parameters did not change throughout the season, greater total number of erythrocytes (P≤0.05), and hemoglobin (P≤0.05) were found at T2 compared to T1. Similarly, lower LDH (P≤0.05) and CK (P≤0.05) levels were found at T2 compared to T1. CPR levels were also decreased at T2 in comparison to T1 both before and after Yo-Yo R2 test (P≤0.05), while IMA and AOPP levels showed only a season effect (P≤0.05). CONCLUSIONS: The tapering strategy was successful considering players presented lower levels of muscle damage, inflammation and oxidative stress makers before T2, which preceded the main championship of the year. These results are of great relevance, considering the team won the FIFA®-Intercontinental-Futsal-Cup, which happened at T2. Thus, it seems that routine-based biochemical markers may be useful as training control means in this population.

Previous physical exercise alters the hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats.

KEY POINTS: An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. ABSTRACT: Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as inhibition of citrate synthase activity) and ion gradient homeostasis (inhibition of Na+ ,K+ -ATPase activity inhibition) when analysed 24 h after TBI. Previous exercise training also protected against dysglycaemia, impaired hepatic signalling (increase in phosphorylated c-Jun NH2-terminal kinase, phosphorylated decreases in insulin receptor substrate and phosphorylated AKT expression), high levels of circulating and neuronal cytokines, the opening of the blood-brain barrier, neutrophil infiltration and Na+ ,K+ -ATPase activity inhibition in the ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioural (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggests that exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence regarding health-related outcomes with respect to a physically active lifestyle.

Diclofenac pretreatment modulates exercise-induced inflammation in skeletal muscle of rats through the TLR4/NF-κB pathway.

Nonsteroidal anti-inflammatory drugs, such as diclofenac, are widely used to treat inflammation and pain in several conditions, including sports injuries. This study analyzes the influence of diclofenac on the toll-like receptor-nuclear factor kappa B (TLR-NF-κB) pathway in skeletal muscle of rats submitted to acute eccentric exercise. Twenty male Wistar rats were divided into 4 groups: control-saline, control-diclofenac, exercise-saline, and exercise-diclofenac. Diclofenac or saline were administered for 7 days prior to an acute eccentric exercise bout. The inflammatory status was evaluated through mRNA levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor alpha (TNF-α), and protein content of COX-2, IL-6, and TNF-α in vastus lateralis muscle. Data obtained showed that a single bout of eccentric exercise significantly increased COX-2 gene expression. Similarly, mRNA expression and protein content of other inflammation-related genes also increased after the acute exercise. However, these effects were attenuated in the exercise + diclofenac group. TLR4, myeloid differentiation primary response gene 88 (MyD88), and p65 were also upregulated after the acute eccentric bout and the effect was blunted by the anti-inflammatory drug. These findings suggest that pretreatment with diclofenac may represent an effective tool to ameliorate the pro-inflammatory status induced by acute exercise in rat skeletal muscle possibly through an attenuation of the TLR4-NF-κB signaling pathway.

Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver.

UNLABELLED: Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-κB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation. AIMS: This study analyzed effects of diclofenac pretreatment on the TLR4/NF-κB pathway in rat liver after an acute eccentric exercise. MAIN METHODS: Twenty male Wistar rats were divided in four groups: control-saline, control-diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout. KEY FINDINGS: After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-κB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-κB pathway and the inflammatory response in the liver of exercised rats. SIGNIFICANCE: Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions.

Protective Effects of Aqueous Extract of Luehea divaricata against Behavioral and Oxidative Changes Induced by 3-Nitropropionic Acid in Rats.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. Accordingly, 3-nitropropionic acid (3-NP) has been found to effectively produce HD-like symptoms. Luehea divaricata (L. divaricata), popularly known in Brazil as "açoita-cavalo," may act as a neuroprotective agent in vitro and in vivo. We evaluated the hypothesis that the aqueous extract of L. divaricata could prevent behavioral and oxidative alterations induced by 3-NP in rats. 25 adult Wistar male rats were divided into 5 groups: (1) control, (2) L. divaricata (1000 mg/kg), (3) 3-NP, (4) L. divaricata (500 mg/kg) + 3-NP, and (5) L. divaricata (1000 mg/kg) + 3-NP. Groups 2, 4, and 5 received L. divaricata via intragastric gavage daily for 10 days. Animals in groups 3, 4, and 5 received 20 mg/kg 3-NP daily from days 8-10. At day 10, parameters of locomotor activity and biochemical evaluations were performed. Indeed, rats treated with 3-NP showed decreased locomotor activity compared to controls. Additionally, 3-NP increased levels of reactive oxygen species and lipid peroxidation and decreased ratio of GSH/GSSG and acetylcholinesterase activity in cortex and/or striatum. Our results suggest that rats pretreated with L. divaricata prior to 3-NP treatment showed neuroprotective effects when compared to 3-NP treated controls, which may be due to its antioxidant properties.

Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects.

Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.

Response of oxidative stress and inflammatory biomarkers to a 12-week aerobic exercise training in women with metabolic syndrome.

BACKGROUND: Evidences have been highlighted the relationship among metabolic syndrome, chronic low-grade inflammation, oxidative stress and several diseases. In this sense, the aim of this study was to investigate the effects of aerobic exercise training on oxidative stress and inflammatory parameters on women with metabolic syndrome (MS). METHODS: Twenty-three untrained women (51.86 ± 6.58 years old, BMI 30.8 ± 4.3 kg/m2) completed a 12-week treadmill exercise training, without modifications on dietary pattern. Advanced oxidation protein products (AOPP), thiobarbituric acid-reactive substances (TBARS), total thiol content (T-SH) and nitrite and nitrate (NOx) levels were assessed in plasma while the levels of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) were evaluated in the serum. The RNA expression (mRNA) of IL-1ß, IL-10, TNF-α, IFN-γ, insulin receptor substrate 2 (IRS-2) and matrix metalloproteinase-9 (MMP-9) were performed inperipheral blood mononuclear cells (PBMC) of a subset with eight women with MS using real real-time polymerase chain reaction (qPCR). RESULTS: The intervention resulted in decreased serum levels of IL-1ß, IL-6, TNF-α, IFN-γ, AOPP and TBARS, besides increased levels of IL-10 and T-SH (P < 0.001). NOx concentrations were unchanged, similarly to mRNA expressions quantified in PBMC. CONCLUSIONS: Twelve weeks of AT improved systemic oxidative stress and inflammatory biomarkers in women with MS, although PBMC mRNA expression for inflammatory pathways appeared to be unchanged. This may indicate that AT induced beneficial effects not only in physical fitness but also on health promotion through decreased oxidative damage and proinflammatory status.

Caffeine intake may modulate inflammation markers in trained rats.

Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO) and acetylcholinesterase (AChE) activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.

Caffeine supplementation modulates oxidative stress markers in the liver of trained rats.

AIMS: Caffeine has been widely used in sports competitions due to its ergogenic effects. Most of the studies regarding caffeine and exercise have focused on muscle and plasma adaptations, while the impact on the liver is scarcely described. The aim is to analyze the effects of caffeine and exercise training on oxidative stress markers and injury-related parameters in the liver. MAIN METHODS: Rats were divided into sedentary/saline, sedentary/caffeine, exercise/saline, and exercise/caffeine groups. Exercise groups underwent 4 weeks of swimming training, and caffeine (6 mg/kg, p.o.) was supplemented throughout the training protocol. Injury-related liver parameters were assessed in plasma, while redox status and oxidative stress markers were measured on liver homogenates. KEY FINDINGS: Exercise training increased muscle citrate synthase activity in the muscle, while in caffeine decreased its activity in both sedentary and trained rats. Aspartate transaminase levels were increased after training, and caffeine intake suppressed this elevation (p<0.05). Caffeine also diminished alanine transaminase levels in both sedentary and exercised rats (p<0.05). Exercise training induced a significant increase on the activity of the enzymes superoxide dismutase and glutathione peroxidase, as an increase on thiobarbituric acid-reactive substances levels was also reached (p<0.05); caffeine intake blunted these alterations. Caffeine intake also suppressed liver catalase activity in both sedentary and exercise groups (p<0.05). SIGNIFICANCE: Our data suggest that caffeine modified the hepatic responses associated to exercise-induced oxidative stress without affecting the performance, exerting different actions according to the tissue. However, further studies are needed to better understand caffeine's role on liver under exercise training.

Guaraná (Paullinia cupana Kunth) effects on LDL oxidation in elderly people: an in vitro and in vivo study.

BACKGROUND: Previous experimental investigations have suggested that guaraná (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guaraná on LDL and serum oxidation. METHODS: The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guaraná (GI) or never ingested guaraná (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guaraná in their diets. The LDL samples were exposed to 5 different guaraná concentrations (0.05, 0.1, 0.5, 1, and 5 µg/mL). RESULTS: GI subjects demonstrated lower LDL oxidation than did NG subjects (reduction of 27%, p < 0.0014), independent of other variables. In the GI group the total polyphenols was positively associated with LDL levels. Also, guaraná demonstrated a high antioxidant activity in vitro, mainly at concentrations of 1 and 5 µg/mL, demonstrated by suppression of CDs and TBARS productions, tryptophan destruction and high TRAP activity. CONCLUSIONS: Guaraná, similar to other foods rich in caffeine and catechins such as green tea, has some effect on LDL oxidation that could partially explain the protective effects of this food in cardiometabolic diseases.

Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats.

The pathology of a gastric ulcer is complex and multifactorial. Gastric ulcers affect many people around the world and its development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. In this study, we evaluated the ethanolic extract of Rosmarinus officinalis L. (eeRo); this plant, more commonly known as rosemary, has attracted the interest of the scientific community due to its numerous pharmacological properties and their potential therapeutic applications. Here, we tested the preventive effects of eeRo against gastric ulcer induced by 70% ethanol in male Wistar rats. In addition, we aimed to clarify the mechanism involved in the preventive action of the eeRo in gastric ulcers. Based on the analysis of markers of oxidative damage and enzymatic antioxidant defense systems, the measurement of nitrite and nitrate levels and the assessment of the inflammatory response, the eeRo exhibited significant antioxidant, vasodilator and antiinflammatory properties.

Effect of different oximes on rat and human cholinesterases inhibited by methamidophos: a comparative in vitro and in silico study.

Methamidophos is one of the most toxic organophosphorus (OP) compounds. It acts via phosphorylation of a serine residue in the active site of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), leading to enzyme inactivation. Different oximes have been developed to reverse this inhibition. Thus, our work aimed to test the protective or reactivation capability of pralidoxime and obidoxime, as well as two new oximes synthesised in our laboratory, on human and rat cholinesterases inhibited by methamidophos. In addition, we performed molecular docking studies in non-aged methamidophos-inhibited AChE to understand the mechanisms involved. Our results suggested that pralidoxime protected and reactivated methamidophos-inhibited rat brain AChE. Regarding human erythrocyte AChE, all oximes tested protected and reactivated the enzyme, with the best reactivation index observed at the concentration of 50 µM. Concerning BChE, butane-2,3-dionethiosemicarbazone oxime (oxime 1) was able to protect and reactivate the methamidophos-inhibited BChE by 45% at 50 µM, whereas 2(3-(phenylhydrazono)butan-2-one oxime (oxime 2) reactivated 28% of BChE activity at 100 µM. The two classical oximes failed to reactivate BChE. The molecular docking study demonstrated that pralidoxime appears to be better positioned in the active site to attack the O-P moiety of the inhibited enzyme, being near the oxyanion hole, whereas our new oximes were stably positioned in the active site in a manner similar to that of obidoxime. In conclusion, our work demonstrated that the newly synthesised oximes were able to reactivate not only human erythrocyte AChE but also human plasma BChE, which could represent an advantage in the treatment of OP compounds poisoning.

Isatin-3-N4-benzilthiosemicarbazone, a non-toxic thiosemicarbazone derivative, protects and reactivates rat and human cholinesterases inhibited by methamidophos in vitro and in silico.

Organophosphates (OPs), which are widely used as pesticides, are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inactivation of AChE results in the accumulation of acetylcholine at cholinergic receptor sites, causing a cholinergic crisis that can lead to death. The classical treatment for OP poisoning is administration of oximes, but these compounds are ineffective in some cases. Here we determined whether the new compound isatin-3-N(4)-benzilthiosemicarbazone (IBTC), which in our previous study proved to be an antioxidant and antiatherogenic molecule, could protect and reactivate AChE and BChE. Toxicity of IBTC after subcutaneous injection in mice was measured using assays for oxidized diclorofluoresceine (DCF), thiobarbituric acid reactive substances (TBARS), non-protein thiol (NPSH) levels, and catalase (CAT), sodium potassium (Na(+)/K(+)) ATPase, delta-aminolevulinic acid dehydratase (ALA-D), and glutathione peroxidases (GPx) enzyme activities. The cytotoxicity was evaluated and the enzymatic activity of cholinesterase was measured in human blood samples. Molecular docking was used to predict the mechanism of IBTC interactions with the AChE active site. We found that IBTC did not increase the amount of DCF-RS or TBARS, did not reduce NPSH levels, and did not increase CAT, (Na(+)/K(+)) ATPase, ALA-D, or GPx activities. IBTC protected and reactivated both AChE and BChE activities. Molecular docking predicted that IBTC is positioned at the peripheral anionic site and in the acyl binding pocket of AChE and can interact with methamidophos, releasing the enzyme's active site. Our results suggest that IBTC, besides being an antioxidant and a promising antiatherogenic agent, is a non-toxic molecule for methamidophos poisoning treatment.