AIMTo evaluate the effects of melatonin (Mel) on oxidative stress in an experimental model of bile duct ligation (BDL).METHODSMale Wistar rats (n = 32, weight ± 300 g) were allocated across four groups: CO (sham BDL), BDL (BDL surgery), CO + Mel (sham BDL and Mel administration) and BDL + Mel (BDL surgery and Mel administration). Mel was administered intraperitoneally for 2 wk, starting on postoperative day 15, at a dose of 20 mg/kg.RESULTSMel was effective at the different standards, reestablishing normal liver enzyme levels, reducing the hepatosomatic and splenosomatic indices, restoring lipoperoxidation and antioxidant enzyme concentrations, reducing fibrosis and inflammation, and thereby reducing liver tissue injury in the treated animals.CONCLUSIONThe results of this study suggest a protective effect of Mel when administered to rats with secondary biliary cirrhosis induced by BDL.

BACKGROUND Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM To evaluate MLT’s effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower ( P < 0.001) n the groups that received MLT. DNA damage was also lower ( P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1β, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT ( P < 0.001). CONCLUSION When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

BACKGROUND Severe acute liver failure (SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function. Thioacetamide (TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2 (Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress. AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκB-mediated inflammation in rats with TAA-induced IHAG. METHODS Male Wistar rats ( n = 28) were divided into four groups: control, control+glutamine, TAA, and TAA + glutamine. Two TAA doses (400 mg/kg) were administered intraperitoneally, 8 h apart. Glutamine (25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione (GSH), Nrf2, Kelch-like ECH-associated protein 1 (Keap1), NADPH quinone oxidoreductase1 (NQO1), superoxide dismutase (SOD)] and inflammatory process. RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatory infiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS ( P < 0.001), GSH ( P < 0.01), IL-1β, IL6, and TNFα levels ( P < 0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP ( P < 0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group ( P < 0.01, P < 0.01, and P < 0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2 ( P < 0.05), NQO1, and SOD ( P < 0.01), as well as levels of IL-10 ( P < 0.001), while decreasing expression of Keap1, TLR4, NFκB ( P < 0.001), COX-2 and iNOS, ( P < 0.01), and reducing NO 2 and NO 3 levels ( P < 0.05). CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway, thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation.

Pretreatment with Gln reduced oxidative, tissue damage and showed a decrease expression of inflammatory mediators.

Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300 g) were divided into four groups: sham-operated (SO), glutamine + SO (G + SO), I/R, and glutamine + I/R (G + I/R). Occlusion of the SMA for 30 min was followed by 15-min reperfusion. Glutamine (25 mg/kg/day) was administered once daily 24 and 48 h before I/R induction. Blood and tissue of were collected for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological analysis, immunohistochemistry of IL-1β and TNF-α, thiobarbituric acid reactive substance (TBARS) and nitric oxide, Nrf2/keap1, superoxide dismutase (SOD), NADPH quinone oxidoreductase1 (NQO1), inducible nitric oxide synthase (iNOS), heat shock protein (HSP70), glucose-regulated protein 78 (GRP78), and activating transcription factor 6 (ATF-6) by western blot. Statistic analysis by ANOVA-Student-Newman-Keuls test (mean ± SE) significantly was p < 0.05. Tissue damage, AST, ALT, IL-1β, TNF-α, TBARS, NO, Keap1, iNOS, GRP78, and ATF-6 expression were significantly lower in the G + I/R group as compared to the I/R group. Expression of Nrf2, SOD, NQO1, and HSP70, was significantly higher in the G + I/R group as compared to I/R group. Pre-treatment with glutamine provided protection against oxidative damage in the intestine and liver in an experimental model of intestinal I/R.

Ulcerative colitis (UC) is an inflammatory disease that affects the bowels. Reactive oxygen species (ROS) are involved in the progress of UC. Objective Evaluate the antioxidant effect of lecithin in an experimental model of acute UC induced by administration of acetic acid (AA) in rats. Methods Lecithin (0.5 mL/kg/day) administered orally 2 days before and after induction of colitis with 4% AA in a volume of 4 mL. Twenty-five male Wistar rats were divided in 5 groups: control (CO); control + lecithin (CO + LE); colitis (CL); colitis + lecithin (CL + LE); lecithin + colitis (LE + CL). Anal sphincter pressure, LPO (TBARS), and antioxidant activity of enzymes superoxide dismutase (SOD) and catalase (CAT) were measured, and a histological analysis with H&E was performed. Results and discussion Anal sphincter pressure was significantly smaller in the CO group, lecithin treatment increased it in pre- and post-treated groups. LPO and SOD activity were increased in the CO group and decreased in the lecithin-treated groups. CAT activity was increased in CO group and decreased in lecithin groups. The histological analysis showed damage to the bowels with destruction of crypts, edema, and inflammatory infiltrate. Use of lecithin preserved the crypts and decreased the edema. Conclusion Ulcerative colitis increased lipid peroxidation, and the use of lecithin was effective reducing damage to the bowels in the model of experimental colitis.

Background: Pulsed radiofrequency (PRF) affects animal and plant tissues; however, the mechanism has not been defined. We hypothesized that the magnetic field produced by PRF exerts its effects by the magnetic sensitivity of transitions between spin states-a spin-correlated radical-pair mechanism (SCRPM)-which, in turn, affects the rates of chemical reactions with participation of paramagnetic species. Objectives: This study aimed to evaluate the effects of PRF on redox equilibrium and inflammatory status in a standard model of muscle injury in rats. Methods: Twenty-four animals were subjected to a single impact trauma to the left quadriceps and the groups exposed and not exposed to PRF were compared. On day 7 of the experiment, the animals were killed and the quadriceps muscles were removed for analysis. Results: There was a significant increase in the concentration of thiobarbituric acid reactive substances (TBARS) in the muscle of animals from the trauma group (+233%), and this increase was eliminated by PRF administration. Superoxide dismutase (SOD) activity was increased (+411%) by trauma, resulting in significantly higher consumption of catalase (-72%), while PRF administration brought both of these markers back to levels close to those of the control group. Trauma induced considerable production of interleukins TNF-α, IL-1β, and IL-6 (+215%, +262%, and +326% vs. controls, respectively) and these effects were also significantly reduced by PRF administration. Conclusions: In total, PRF inhibits oxidative stress and restores antioxidant enzymes to control levels and may block production of inflammatory markers in muscles of animals subjected to trauma. By modulating redox equilibrium, PRF treatment might block production of noxious mediators involved in development of trauma-induced injury.

-Background -Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. Objective -To evaluate the antioxidant effect of vitamin E in this ALF model. Methods -We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P<0.05 considered as significant. The histopathological evaluation showed a decrease in liver injury (necrosis and inflammation) in both studied times. Conclusion -These results suggest that vitamin E was able to protect the liver from lesions caused by thioacetamide. HEADINGS -Acute liver failure. Thioacetamide. Oxidative stress. Antioxidants.