Liver Oxidative Status Research Articles

Effects of weight loss on liver and erythrocyte polyunsaturated fatty acid pattern and oxidative stress status in obese patients with non-alcoholic fatty liver disease.

Our aim was to study the influence of weight loss on the fatty acid (FA) composition of liver and erythrocyte phospholipids and oxidative stress status in obese, non-alcoholic, fatty liver disease (NAFLD) patients. Seven obese NAFLD patients who underwent subtotal gastrectomy with a gastro-jejunal anastomosis in roux and Y were studied immediately and 3 months after surgery. Seven non-obese patients who underwent anti-reflux surgery constituted the control group. Serum F2-isoprostane levels were measured by GS/NICI-MS/MS and FA composition was determined by GC. At the time of surgery, controls and obese patients exhibited a hepatic polyunsaturated fatty acid (PUFA) pattern that correlated with that of erythrocytes. Three months after surgery, NAFLD patients lost 21% of initial body weight; serum F2-isoprostane levels decreased by 76%; total PUFA, long-chain PUFA (LCPUFA), n-3 PUFA, and n-3 LCPUFA increased by 22, 29, 81, and 93%, respectively; n-6/n-3 LCPUFA ratio decreased by 51%; docosahexaenoic acid/docosapentaenoic acid ratio increased by 19-fold; and the n-3 product/precursor ratio (20: 5 + 22: 5 + 22: 6)/18: 3 increased by 164% (p<0.05). It is concluded that weight loss improves the n-3 LCPUFA status of obese patients in association with significant amelioration in the biomarkers of oxidative stress, membrane FA insaturation, and n-3 LCPUFA biosynthesis capacity, thus representing a central therapeutic issue in the improvement of obesity-related metabolic alterations involved in the mechanism of hepatic steatosis.

Effects of weight loss on liver and erythrocyte polyunsaturated fatty acid pattern and oxidative stress status in obese patients with non-alcoholic fatty liver disease

Our aim was to study the influence of weight loss on the fatty acid (FA) composition of liver and erythrocyte phospholipids and oxidative stress status in obese, non-alcoholic, fatty liver disease (NAFLD) patients. Seven obese NAFLD patients who underwent subtotal gastrectomy with a gastro-jejunal anastomosis in roux and Y were studied immediately and 3 months after surgery. Seven non-obese patients who underwent anti-reflux surgery constituted the control group. Serum F2-isoprostane levels were measured by GS/NICI-MS/MS and FA composition was determined by GC. At the time of surgery, controls and obese patients exhibited a hepatic polyunsaturated fatty acid (PUFA) pattern that correlated with that of erythrocytes. Three months after surgery, NAFLD patients lost 21% of initial body weight; serum F2-isoprostane levels decreased by 76%; total PUFA, long-chain PUFA (LCPUFA), n-3 PUFA, and n-3 LCPUFA increased by 22, 29, 81, and 93%, respectively; n-6/n-3 LCPUFA ratio decreased by 51%; docosahexaenoic acid/docosapentaenoic acid ratio increased by 19-fold; and the n-3 product/precursor ratio (20: 5 + 22: 5 + 22: 6)/18: 3 increased by 164% (p<0.05). It is concluded that weight loss improves the n-3 LCPUFA status of obese patients in association with significant amelioration in the biomarkers of oxidative stress, membrane FA insaturation, and n-3 LCPUFA biosynthesis capacity, thus representing a central therapeutic issue in the improvement of obesity-related metabolic alterations involved in the mechanism of hepatic steatosis.

Hypertaurinemia in Bile Duct–Ligated Rats After Surgery: The Effect of Gut Endotoxin Restriction on Organ Fluxes and Oxidative Status

Surgery in obstructive jaundice is associated with complications related to gut-derived endotoxemia. The organs involved in these complications, including liver, kidneys, and gut, are important in the metabolism of taurine, which is implicated in bile acid conjugation and has antioxidative effects. Taurine organ metabolism and liver oxidative status were studied in bile duct-ligated rats (BDL) after laparotomy. Oral cholestyramine treatment inhibits gut-derived endotoxemia and was used to evaluate the role of endotoxin. In BDL rats, postoperative plasma taurine levels were higher compared with SHAM (p < .0001). Cholestyramine treatment reduced plasma taurine in BDL rats (p < .005), but levels remained higher compared with SHAM groups (p < .0001). In contrast to a liver uptake of taurine in SHAM rats, a release from livers of BDL rats was found (p < .005). Cholestyramine treatment in BDL rats resulted in a liver uptake of taurine (p < .05 vs BDL). A higher uptake of taurine by the kidneys was found in both BDL animals after surgery and SHAM controls (p < .005); however, cholestyramine had no effect. A release of taurine from the gut was found in the SHAM groups, which was reversed in both BDL groups (p < .01). Cholestyramine lowered the elevated levels of hepatic enzymes in BDL rats (ALT and AST: p < .05). Total liver glutathione levels were lower in BDL rats (p < .0001) compared with SHAM groups, and cholestyramine significantly attenuated this decrease (p < .01). Liver malondialdehyde levels were higher in BDL rats compared with SHAM (p < .01), whereas cholestyramine completely prevented this increase in lipid peroxidation (p < .0001). Hypertaurinemia in BDL rats after surgery is most likely explained by reduced bile acid conjugation and hepatocellular leakage. Cholestyramine treatment reduced hepatocellular damage by inhibiting gut-derived endotoxemia, and reversed the release of taurine from the jaundiced liver into an uptake and consequently lowered plasma taurine levels. This uptake may contribute to the improved antioxidant status in cholestyramine-treated BDL rats.

METABOLIC STATUS DETERMINES CHANGES IN THE ANTIOXIDANT SYSTEM AND LIPOPEROXIDATION IN SLEEP DEPRIVED RATS

We verified the effects of sleep deprivation on blood and liver oxidative status of rats. Thirty male rats, living under controlled conditions with chow pellets and water ad libitum, were housed individually and signed as control (CTR), sleep deprived for 96h by the platform technique (SD-96h) and SD-96h recovered for 24h (REB) groups. Immediately after sleep deprivation blood and liver samples were collected to measure the levels of: Cu/Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total glutathione (tGSH) and lipid peroxidation potential accessed as thiobarbituric acid reactive substances (TBARS). Body weight (BW) was strictly reduced in SD-96h (−6.23±2.58%) and REB (−7.10±2.31%) groups compared to CTR (+1.08±1.54%). Blood parameters showed reduced erythrocyte tGSH in SD-96h and REB groups compared to CTR. Meanwhile, liver oxidative stress markers showed reductions in SD-96h and REB groups on tGSH, CAT and TBARS levels. Correlation analysis showed a relationship between BW changes and erythrocyte tGSH (r=0.65), liver tGSH (r=54), liver CAT (r=0.73) and liver TBARS (r=0.49). Although reductions in erythrocyte and liver tGSH and liver CAT could suggest that sleep deprivation produces oxidative stress, it was not reinforced by blood and liver TBARS. Further, the correlation between all oxidative stress parameters modified by sleep deprivation and BW changes are in line to the proposal that metabolic status modifies free radical-scavenging system, and therefore it is important to differentiate the effects of BW reduction and sleep disturbance itself.

Effects of hyperbaric oxygen treatment on liver functions, oxidative status and histology in septic rats

The liver is thought to be responsible for multiple organ failure during sepsis. Increase in tissue oxygen consumption is a major component of the septic response. Hyperbaric oxygen (HBO) therapy provides more oxygenation in the whole body. This study examined the effect of HBO alone or in combination with cefepime (CEF) on the liver in septic rats. We divided 90 male rats into six groups; control, HBO, sepsis (SEP), SEP+HBO, SEP+CEF, and SEP+CEF+HBO. Sepsis was induced with an intraperitoneal injection of Escherichia coli (2.1 x 10(9) cfu). A total of six HBO sessions were performed at 2 atm absolute for 90 min at 6-h intervals. CEF was administered intraperitoneally at a dose of 50 mg/kg twice daily. Animals were killed 48 h after sepsis induction. Their liver and blood were removed for biochemical and histopathological analysis. Liver thiobarbituric acid reactive substances as well as serum alanine transaminase, aspartate transaminase and alkaline phosphatase levels increased while the activity of the antioxidant enzymes superoxide dismutase and catalase decreased significantly in septic rats. These parameters returned to nearly control levels in the SEP+CEF+HBO group. Histological observations supported these findings: Hepatocellular degeneration was observed and intensive polymorphonuclear cell infiltration appeared in all fields of septic animal livers. HBO alone could not sufficiently reverse these histopathological changes, but most liver sections presented normal histology when it was combined with CEF. HBO may be a useful adjuvant therapy modality to improve the efficacy of sepsis treatment.

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL+BBS (10 μg/kg, s.c. ×3), BDL+NT (300 μg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.

Effects of Silymarin MZ-80 on Hepatic Oxidative Stress in Rats with Biliary Obstruction

This study was designed to evaluate the effects of three pharmaceutical forms of silymarin (silymarin MZ-80, silybinin-β-cyclodextrin, and silybinin) on the liver oxidative status in vitro and after oral administration to rats with extrahepatic biliary obstruction (EBO) and sham-operated animals. We evaluated thiobarbituric acid-reactive substances (TBARS), glutathione (GSH + GSSG) and their related enzyme activities (GSH peroxidase, GSSG reductase and GSH transferase). All three compounds inhibited the in vitro production of TBARS (IC₅₀ 56–533 µmol/l). These compounds, mainly silymarin MZ-80, also increased GSH peroxidase and GSH transferase activities. In EBO rats we found increases in TBARS production which was inhibited by 50–70% after treatment. Glutathione was reduced by 55% and elevated by silymarin MZ-80. GSH transferase increased in the group given silymarin MZ-80. We conclude that all three derivatives of silymarin show a clear ability to reduce lipid peroxidation in the liver. Silymarin MZ-80 was the only compound that enhanced the glutathione antioxidant system.

Effects of aging on the susceptibility to the toxic effects of cyclosporin A in rats. Changes in liver glutathione and antioxidant enzymes

Free radicals are involved in aging and cyclosporin A-induced toxicity. The age-related changes in the liver oxidative status of glutathione, lipid peroxidation, and the activity of the enzymatic antioxidant defense system, as well as the influence of aging on the susceptibility to the hepatotoxic effects of cyclosporin (CyA) were investigated in rats of different ages (1, 2, 4, and 24 months). The hepatic content of reduced glutathione (GSH) increased with aging, peaked at 4 months, and decreased in senescent rats. By contrast, glutathione disulfide (GSSG) and thiobarbituric acid-reactive substances (TBARS) concentrations and superoxide dismutase, catalase, and glutathione peroxidase activities were higher in the oldest than in the youngest rats. CyA treatment, besides inducing the well-known cholestatic syndrome, increased liver GSSG and TBARS contents and the GSSG/GSH molar ratio, and altered the nonenzymatic and enzymatic antioxidant defense systems. The CyA-induced cholestasis and hepatic depletion of GSH, and the increases in the GSSG/GSH ratio, and in GSSG and TBARS concentrations were higher in the older than the mature rats. Moreover, superoxide dismutase and catalase activities were found to be significantly decreased only in treated senescent rats. The higher CyA-induced oxidative stress, lipoperoxidation, and decreases in the antioxidant defense systems in the aged animals render them more susceptible to the hepatotoxic effects of cyclosporin.

Beer affects oxidative stress due to ethanol in rats.

The relationship between chronic moderate beer consumption and oxidative stress was studied in rats. Animals were fed three different isocaloric diets for six weeks: a beer-containing diet (30% w/w), an ethanol-supplemented diet (1.1 g/100 g, the same as in the beer diet) and an alcohol-free basal diet. At the end of the feeding period, rats were analyzed for plasma and liver oxidative status. Some livers were isolated and exposed to ischemia-reperfusion to assess the additional oxidative stress determined by reperfusion. No significant differences in plasma antioxidant status were found among the three dietary groups. Lipoproteins from the beer group, however, showed a greater propensity to resist lipid peroxidation. Ischemia caused a decrease in liver energy and antioxidant status in all groups. Nevertheless, ATP was lower in the livers of rats exposed to the ethanol diet. During reperfusion, lipoperoxidation increased significantly in all groups. However, livers obtained from ethanol-treated rats showed the higher formation of lipoperoxides. In conclusion, a moderate consumption of beer in a well-balanced diet did not appear to cause oxidative stress in rats; moreover, probably through its minor components, beer could attenuate the oxidative action of ethanol by itself.

Oxidative stress in gill, erythrocytes, liver and kidney of Nile tilapia ( Oreochromis niloticus) from a polluted site

A comparison between some pro- and antioxidant parameters in erythrocyte, gill, liver and kidney of Nile tilapia, O. niloticus from a fish farm (Control group) and from a polluted site in the Billings Reservoir (Reservoir group) was done. No hematological alterations were observed in blood of Billings fish. The erythrocyte oxidative stress was characterized by increased oxygen uptake and decreased induction time (induced by t-butyl hydroperoxide, t-BHP) evidencing a higher susceptibility to oxidative damage. Moreover, beside the augmented erythrocyte superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH) and glutathione peroxidase activities, a decrease in both catalase (CAT) activity and total glutathione content (GSH), in erythrocytes of Reservoir fish was observed. The higher cytochrome b 5 levels observed in the gill microsomal fraction is likely to be the cause of the enhanced oxyradical production. This fact, associated with the diminished CAT and G6PDH activities, accounts for a gill oxidative stress of Reservoir fish. Except for the NADPH-cytochrome P-450 (c) reductase activity, the other liver pro-oxidant parameters were greatly increased in the Reservoir fish. These results together with the increase in SOD activity and decrease in CAT, glutathione reductase (GR) and G6PDH activities indicated a liver oxidative stress status. The observed increases in kidney NADH cytochrome c reductase and in both cytochromes P-450 and b 5 contents were not reflected in enhanced oxyradical production, suggesting a well coupled P-450 catalytic cycle in this tissue. However, the antioxidant enzymes had a similar pattern in liver. The decrease in GSH observed in kidney is probably associated with conjugation reactions for subsequent excretion. All these results furnish useful data for future investigations of polluted aquatic sites in order to provide a data base relating the presence of pollutants to biological effects at a molecular level.