Effect of dietary vitamin E and Santoquin on regenerating rat liver

The influence of dietary vitamin E and Santoquin on lipid peroxidation and liver regeneration in partially-hepatectomized rats was studied. Rats were fed either a basal 10% tocopherol-stripped corn oil diet, the basal diet plus 40 mg dl-alpha-tocopheryl acetate/kg, or the basal diet plus 2 g Santoquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline)/kg. After 6 weeks, rats fed the antioxidant-deficient diet produced more of the lipid peroxidation product, pentane, than did the rats fed antioxidants. Partial hepatectomy was performed after six and one-half weeks or ten weeks of feeding the diets. At 3 and 6 days after surgery, pentane production was significantly elevated over pre-surgery levels in rats fed the antioxidant-deficient or vitamin E-supplemented diets, but not in rats fed the Santoquin-supplemented diet. Six days after surgery, there were fewer thiobarbituric acid reactants in regenerating liver of Santoquin-fed rats than of vitamin-E fed rats or antioxidant-deficient rats. There was no increase in the 6-day level of thiobarbituric acid reactants over the 3-day level in livers of rats fed Santoquin, while there was an increase in livers of the antioxidant-deficient and vitamin E-supplemented rats. Liver sulfhydryl levels were higher at 3 and 6 days post surgery in the Santoquin-fed rats than in the antioxidant-deficient or vitamin E-supplemented rats. Plasma gamma-glutamyl-transpeptidase activity was not different among the groups of rats. Between the third and sixth day following surgery, liver regeneration was significantly stimulated in Santoquin-fed, but not vitamin E-fed rats. After 11 days, a stimulatory, but not statistically significant, effect of vitamin E was found. Although DNA content of liver was higher at 6 days than at 3 days post surgery, it was not different among the dietary groups, indicating that cell proliferation rather than hypertrophy had occurred. Partial hepatectomy could have altered the ability of the liver to metabolize pentane, thus explaining part of the increased production of pentane. However, the results obtained support the interpretation that elevated levels of dietary antioxidants can be beneficial in terms of reduced lipid peroxidation and increased rates of liver regeneration following liver surgery.     

The effect of iron overload on urinary excretion of immunoreactive prostaglandin E2

The effect of in vivo lipid peroxidation on the excretion of immunoreactive prostaglandin E2 (PGE2) in the urine of rats was studied. Weanling, male Sprague-Dawley rats were fed a vitamin E-deficient diet containing 10% tocopherol-stripped corn oil (CO) or 5% cod liver oil (CLO) with or without 40 mg dl-alpha-tocopheryl acetate/kg. To induce a high, sustained level of lipid peroxidation, some rats were injected intraperitoneally with 100 mg of iron as iron dextran after 10 days of feeding. Iron overload stimulated in vivo lipid peroxidation in rats, as measured by the increase in expired ethane and pentane. Dietary vitamin E reversed this effect. Rats fed the CLO diet excreted 9.5-fold more urinary thiobarbituric acid-reactive substances (TBARS) than did rats fed the CO diet. Iron overload increased the excretion of TBARS in the urine of rats fed the CO diet, but not in urine of rats fed the CLO diet. Dietary vitamin E decreased TBARS in the urine of rats fed either the CO or the CLO diet. Iron overload decreased by 40% the urinary excretion of PGE2 by rats fed the CO diet, and dietary vitamin E did not reverse this effect. Iron overload had no statistically significant effect on urinary excretion of PGE2 by rats fed the CLO diet. A high level of lipid peroxidation occurred in iron-treated rats, as evidenced by an increase in alkane production and in TBARS in urine in this study, and by an increase in alkane production by slices of kidney from iron-treated rats in a previous study [V. C. Gavino, C. J. Dillard, and A. L. Tappel (1984) Arch. Biochem. Biophys. 233, 741-747]. Since PGE2 excretion in urine was not correlated with these effects, lipid peroxidation appears not to be a major factor in renal PGE2 flux.     

Effect on Lipids in Liver and Serum,and Some Urinary Components of Dietary Supplement of Excess Lysine Given to Previously Starved or Non-starved Rats

In order to obtain further information on the changes in liver lipids, either a basal or a lysine-sexcess diet was refed to previously starved rats or fed to previously non-starved rats. Liver lipid accumulation was observed in previously starved rats refed the lysine-excess diet for 7 days, but not in rats without previous starvation. The liver lipid did not accumulate with another 8 days’ feeding (15 days⁹ refeeding). The addition of methionine alone or in combination with threonine to the lysine-excess diet had no effect on the liver lipid level. The decrease in serum triacylglycerol in rats refed the lysine-excess diet was preceded by lipid accumulation in the liver. Urinary potassium during the initial two days increased with refeeding and feeding. Marked excretion of orotate was observed for 2 days from the initiation of refeeding of the lysine-excess diet and it then decreased. Thus, such a marked increase in the urinary excretion of orotate might be associated with the stimulation of orotate biosynthesis and with lipid accumulation in the liver.     

Influence of reduced glutathione on changes in the activity of phospholipase C induced by 4-hydroxynonenal

4-Hydroxynonenal (HNE) is a major end-product of lipid peroxidation. 1 mM HNE inhibits the activity of liver phospholipase C (PL-C) and this effect is prevented by 1 mM GSH; on the contrary GSH is unable to counteract the stimulation of PL-C induced by a low concentration of HNE (100 nM). Other hydroxyalkenals are able to stimulate PL-C at low doses (micromolar or less), the most effective being 4-hydroxyoctenal which acts at picomolar doses. The lack of a correlation between the chain length of the aldehydes used and the degree of PL-C stimulation seems to exclude the possibility that their effect could be due to an aspecific solvent action toward the phosphatidylinositol-4,5-diphosphate used as substrate for the enzymatic assay.     

Stimulation of lipid peroxidation by methyl mercury in rats

As an index lipid peroxidation, thiobarbituric acid (TBA)-reactive substances in the liver, kidney, and serum, and hydrocarbons (ethane and pentane) in the exhalation of rats injected subcutaneously with 10 mg/kg/day of methylmercuric chloride (MMC) were determined. Formation of TBA-reactive substances in the liver and kidney of rats was significantly increased 4 and 2 days after initial injection of MMC, respectively. The result for serum was similar to that for the kidney. The maximum ethane production in the exhaled gases was observed 4 days after initial injection of MMC, and thereafter decreased slowly. Pentane production was significantly increased 5 days after initial injection of MMC, and thereafter continued to increase. Glutathione peroxidase activity and amount of vitamin C in the liver were depleted 4 days after initial injection of MMC; vitamin E was not depleted. In the kidney, significant decreases of glutathione peroxidase activity and vitamin C content were also seen 4 days after initial injection of MMC, but vitamin E content was unaltered.Thus, a clear increase of lipid peroxidation as determined by measurement of TBA-reactive substances in tissues and of hydrocarbons in the exhaled gases of rats after MMC treatment was demonstrated, though there was a lag phase of several days before the increase of lipid peroxidation. It is suggested that the significant increase of lipid peroxide formation may be a result of depletion of defending factors against lipid peroxidation.     

The oxidation of benzo[a]pyrene-7,8-dihydrodiol mediated by lipid peroxidation in the rat intestine and the effect of dietary lipids

This study has demonstrated that the microsomal fraction of the rat small intestinal mucosa has the capacity to catalyse the oxidation of benzo[a]pyrene(BP)-7,8-diol to BP-diol-epoxides (BPDEs) both by a mechanism involving the mixed-function oxidase system (NADPH-dependent) and as a result of the initiation of peroxidation of the membrane phospholipids by ferrous ions, ascorbate and ADP. The NADPH-dependent reaction was fastest in the proximal part of the intestine and resulted in the formation of approximately equal amounts of BPDE I and BPDE II. The lipid peroxidation-catalysed reaction favoured the production of BPDE I and was maximal in the middle region of the intestine, closely paralleling the rate of lipid peroxidation in the intestinal sections. Feeding rats on a cod liver oil diet, rich in C20:5 and C22:6, significantly increased the incorporation of these fatty acids into the microsomal fractions. This resulted in a greatly increased rate of lipid peroxidation in vitro and a significantly higher rate of lipid peroxidation-catalysed BP-7,8-diol oxidation compared to rats fed fat-free, mono-unsaturated lard or corn oil (58% C18:2) diets. Thus the rate of conversion of BP-7,8-diol to its ultimate carcinogenic forms during lipid peroxidation in the intestinal fractions of rats fed a polyunsaturated fat was quantitatively more important than the NADPH-catalysed reaction as measured in vitro.     

The effects of in vitro lipid peroxidation on the activity of rat liver microsomal glutathione S-transferase from rats supplemented or deficient in antioxidants

Glutathione S-transferases are a group of multifunctional isozymes that play a central role in the detoxification of hydrophobic xenobiotics with electrophilic centers (1). In this study we investigated the effects of in vitro lipid peroxidation on the activity of liver microsomal glutathione S-transferases from rats either supplemented or deficient in both vitamin E and selenium. Increased formation of malondialdehyde (MDA), a by-product of lipid peroxidation, was associated with a decreased activity of rat liver microsomal glutathione S-transferase. The inhibition of glutathione S-transferase occurred rapidly in microsomes from rats fed a diet deficient in both vitamin E and selenium (the B diet) but was delayed for 15 minutes in microsomes from rats fed the same diet but supplemented with these micro-nutrients (B+E+Se diet). Lipid peroxidation inhibits microsomal glutathione S-transferase and this inhibition is modulated by dietary antioxidants.     

Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development

The protection of the developing organism from oxidative damage is ensured by antioxidant defense systems to cope with reactive oxygen species (ROS), which in turn can be influenced by dietary polyunsaturated fatty acids (PUFAs). PUFAs in membrane phospholipids are substrates for ROS-induced peroxidation reactions. We investigated the effects of dietary supplementation with omega-3 PUFAs on lipid peroxidation and antioxidant enzyme activities in rat cerebrum, liver and uterus. Pups born from dams fed a diet low in omega-3 PUFAs were fed at weaning a diet supplying low α-linolenic acid (ALA), adequate ALA or enriched with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Malondialdehyde (MDA), a biomarker of lipid peroxidation, and the activities of superoxide dismutase 1 (SOD1), SOD2, catalase (CAT) and glutathione peroxidase (GPX) were determined in the three target organs. Compared to low ALA feeding, supplementation with adequate ALA or with EPA + DHA did not affect the cerebrum MDA content but increased MDA content in liver. Uterine MDA was increased by the EPA + DHA diet. Supplementation with adequate ALA or EPA + DHA increased SOD2 activity in the liver and uterus, while only the DHA diet increased SOD2 activity in the cerebrum. SOD1, CAT and GPX activities were not altered by ALA or EPA + DHA supplementation. Our data suggest that increased SOD2 activity in organs of the growing female rats is a critical determinant in the tolerance to oxidative stress induced by feeding a diet supplemented with omega-3 PUFAs. This is may be a specific cellular antioxidant response to ROS production within the mitochondria.     

Elevation of thiobarbituric acid values in the rat liver intoxicated by T-2 toxin

In the present study we first demonstrated that T-2 toxin markedly stimulated lipid peroxidation specifically in the liver of rats. The amount of lipid peroxides in the liver, estimated by the thiobarbituric acid (TBA) method, increased dose dependently, being proportional to the extent of its acute toxicity measured by various parameters in rats fed a commercial diet. Further, to elucidate the mechanism of lipid peroxidation and its role in hepatic injury caused by T-2 toxin, time-course studies on the correlation between lipid peroxide content and some biological and histopathological data were undertaken in rats given 4 mg of the toxin/kg perorally. The TBA reactive substances in the liver began to increase after 6 hr. However, much earlier than this there were some other alterations, which included decreases in the amount of cytochrome P-450 in the liver, of GPT (thereafter an increase) and phospholipids in the plasma, and of basophilic masses in the hepatocytes (arrayed as a rough endoplasmic reticulum in the electron micrograph). The vitamin E-deficient study showed that vitamin E markedly inhibited the stimulative effect of T-2 toxin on lipid peroxidation, but not diminish any other measured parameters of the injury. The toxin-induced stimulation of lipid peroxidation does not appear to be caused by activation of microsomal NADPH-cytochrome c reductase nor by a decrease in the level of cytosolic glutathione peroxidase. These results suggest that T-2 toxin might induce some alteration of the membrane structure and consequently might stimulate lipid peroxidation in situ.     

Preventive effects of dehydroepiandrosterone acetate on the fatty liver induced by orotic acid in male rats.

Preventive effects of dehydroepiandrosteone acetate (DHEA-A) and clofibrate (positive control substance) on the fatty liver induced by orotic acid (OA) were examined on the male Sprague-Dawley rats fed a high sucrose based diet containing 1% OA and this diet further mixed with 0.5% DHEA-A or 0.5% clofibrate for 2 weeks. Numerous lipid droplets were observed in the hepatocytes of the rats treated with OA alone, but not in those treated with DHEA-A or clofibrate. In comparison to the group with OA alone, the DHEA-A or clofibrate treated rats showed a larger relative liver weight (to body weight) which was accompanied by increased peroxisomes in the hepatocytes. These results indicate that DHEA-A, as well as clofibrate, may prevent OA-induced fatty liver.     

Effect of citrate feeding on free radical induced changes in experimental urolithiasis.

Feeding calculi producing diet (CPD) to rats for 4 weeks produced calcium oxaltate stones. Supplementation of sodium citrate to CPD (c-CPD) prevented stone formation. Except oxalate, the excretion of calcium, phosphorus and magnesium was restored to normal in c-CPD fed rats. The CPD fed rats exhibited increase in glycolic acid oxidase (GAO) and lactate dehydrogenase (LDH) activities and only GAO activity was partially restored in c-CPD fed rats. Kidney sub-cellular fractions of calculi producing diet (CPD) fed rats showed increased susceptibility for lipid peroxidation in presence of promotors. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase and glutathione peroxidase and antioxidant concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin E were significantly decreased while the xanthine oxidase activity, and concentrations of hydroxyl radical, diene conjugates and hydroperoxides were significantly increased in CPD fed rats. The susceptibility to lipid peroxidation, activities of antioxidant enzymes, and the concentration of antioxidants were not normalized by feeding citrate.     

Phospholipid Hydroperoxides and Lipid Peroxidation in Liver and Plasma of ODS Rats Supplemented with α-Tocopherol and Ascorbic Acid

Forty-five mutant male ODs rats, unable to synthesize ascorbic acid, were fed nine diets containing 5, 50 or 250 mg of vitamin E/kg diet and 150,300 or 900 mg of vitamin C/kg diet for 21 days. The concentrations of vitamins C and E increased in liver and plasma in relation to the level of these vitamins in the diet. Vitamin C dietary supplementation increased the plasma vitamin E content at low levels of vitamin E intake, supporting the concept of an in vivo synergism between both antioxidant vitamins. Vitamin C, at the dietary levels studied, did not affect the lipid peroxidation. Vitamin E decreased liver and plasma endogenous levels of thiobarbituric acid-reactive substances and liver sensitivity to non-enzymatic lipid peroxidation. This was confirmed by a highly specific assay of lipid hydroperoxides using high performance liquid chromatography with chemiluminescence detection. The hepatic concentration of both phosphatidylcholine and phosphatidylethanolamine hydroperoxides decreased as the vitamin E content of the diet increased. The results show for the first time the capacity of vitamin E to protect against peroxidation of major phospho-lipids in vivo under basal unstressed conditions.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats.     

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl₄)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.     

Pregnenolone and dexamethasone, modulators of cytochrome P450-3A, not increase but reduce urinary alpha-CEHC excretion in rats

In this study, the CYP3A inducer pregnenolone-16alpha-carbonitrile (PCN) and the CYP3A inhibitor ketoconazole (KCZ) were used to investigate whether the metabolism of alpha-tocopherol to its metabolite, alpha-carboxyethyl hydroxychroman (alpha-CEHC), is CYP3A-dependent in rats. In experiment 1, two groups of Wistar rats were fed for 3 wk with either a basal diet (containing 50~ppm of alpha-tocopherol) or the same diet containing 10-fold more alpha-tocopherol. In the last 3 days, each group was divided into 2 subgroups which were given a single i.p. injection of either PCN at 75 mg/kg/d (P50 & P500 groups) or DMSO (D50 & D500 groups). The liver TBARS concentration was highest in the P50 group. Two-way ANOVA analysis showed that alpha-tocopherol levels in the plasma and liver were both significantly decreased by PCN (p < 0.0001), as were alpha-CEHC levels in the urine (p = 0.0004). In experiment 2, alpha-tocopherol levels in the liver were increased and alpha-CEHC excretion in the urine decreased in the Wistar rats fed with KCZ containing diet. In experiment 3, Wistar rats administered with dexamethasone (DEX) significantly decreased alpha-tocopherol levels in the plasma and liver and alpha-CEHC levels in the urine. These data showed CYP3A is not a major contributor of the metabolism of alpha-tocopherol to alpha-CEHC. Nevertheless, vitamin E status was markedly reduced by CYP3A inducers due to increased lipid peroxidation and this would increase the consumption of alpha-tocopherol in the liver.     

Fenofibrate prevents orotic acid--induced hepatic steatosis in rats

The experiments performed in this report were designed to investigate the mechanisms involved in the metabolic alterations associated with orotic acid-induced hepatic steatosis and the effect of fenofibrate, a stimulant of peroxisome proliferators-activated receptor alpha (PPARalpha), on these alterations. Male Wistar rats were divided into three experimental groups: 1) fed a balanced diet (C); 2) fed a balanced diet supplemented with 1% orotic acid (OA); 3) fed OA diet containing 100 mg.kg(-1) bw.day(-1) fenofibrate (OA+F), for 9 days. Administration of OA to rats induced significant increase in the hepatic total lipids content, marked microvesicular steatosis and decrease in plasma lipids concentrations compared to control group. Fenofibrate treatment prevented fatty liver induction, caused an additional reduction on plasma lipids concentrations and caused a 40% decrease in the lipogenic rate in adipose tissue. The results also showed a 40% increase in lipoprotein lipase (LPL) activity in adipose tissue from OA treated group and fenofibrate administration induced a 50% decrease in LPL activity. The liver mRNA expression of PPARalpha and ACO (acyl CoA oxidase) were 85% and 68% decreased in OA group when compared to control, respectively. Fenofibrate treatment increased the PPARalpha and ACO expressions whereas the CPT-1 (carnitine palmitoyl transferase-1) expression was not altered. Our results have shown that fenofibrate treatment decreases the hepatic lipid content induced by OA which is mediated by an important increase in fatty acid oxidation consequent to an increase in hepatic mRNA expression of PPARalpha and ACO.     

Antioxidant status and mineral contents in tissues of rutin and baicalin fed rats

The versatile benefit effects of flavonoids lead some nutritionists to believe that they are micronutrients. However, excess intake of flavonoids may cause side effects. In this paper, the effects produced by a higher intake of rutin and baicalin on antioxidant status as well as trace minerals such as iron, copper and zinc in rat tissues were studied. When rats were fed a rutin or baicalin containing diet (1%) for 20 days, the body weight gain was lower than that of the control group. Both rutin and baicalin caused significant a decrease of catalase activity and a moderate increase of total superoxide dismutase activity in the liver. The total antioxidant status of flavonoid fed rats was increased in the liver but decreased in the serum. In comparison to the control group, the lipid peroxidation level in the liver of the rutin fed group was significantly decreased; however, there was no statistical significance in the liver of the baicalin fed group and the brain of both flavonoids groups. The liver homogenates of both flavonoid fed rats significantly inhibited alkyl radical-induced lipid peroxidation. The iron contents in the liver of flavonoid fed rats were significantly decreased; rutin also caused zinc and copper decrease in the liver. These results indicated that high flavonoid intake can improve rat antioxidant systems in the liver; while it can also cause a trace mineral decrease and, in turn, reduce the activities of some metal-containing enzymes and may cause harmful effects on health.     

Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol

To investigate the effect of dietary chitosan on lipid metabolism, male SD (Sprague-Dawley) rats were fed a cholesterol-enriched diet containing 5% cellulose (CE), 5% chitosan (CCS; high viscosity), or 5% chitosan (FCS; low viscosity) for 4 weeks. The two types of chitosan with a comparable degree of deacetylation had a different molecular weight and intrinsic viscosity. Significantly (p < 0.05) lower plasma total cholesterol, LDL-cholesterol and VLDL-cholesterol concentrations were observed in the rats fed on the chitosan diets. In addition, chitosan significantly increased the fecal cholesterol and triglyceride contents. Although no significant difference in body weight was found among the dietary groups, the rats fed on the chitosan diets had lower relative liver weight when compared with those fed on the cellulose diet. Both of the chitosan groups had significantly lower liver total lipid and total cholesterol contents compared to the cellulose group, although the FCS group was less effective. The plasma and liver thiobarbituric acid reactive substances (TBAR) values were similar in the CE and FCS groups, while the CCS group had increased liver TBAR values. Although a significant increase in liver glucose-6-phosphate dehydrogenase activity was observed in the CCS group, no significant change was found in the FCS group. The observed influence of chitosans with different viscosity on the plasma lipid level, liver lipids and lipid peroxidation suggests that, while the hypocholesterolemic action of chitosans with different viscosity was similar, changes in the liver lipids and liver peroxidation status depended on their molecular weight when the deacetylation degree was comparable.     

Taurine: Protective properties against ethanol-induced hepatic steatosis and lipid peroxidation during chronic ethanol consumption in rats

Summary Alcohol was administered chronically to female Sprague Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in hepatic steatosis and lipid peroxidation. Taurine, when co-administered with alcohol, reduced the hepatic steatosis and completely prevented lipid peroxidation. The protective properties of taurine in preventing fatty liver were also demonstrated histologically. Although alcohol was found not to affect the urinary excretion of taurine (a non-invasive marker of liver damage), levels of serum and liver taurine were markedly raised in animals receiving alcohol + taurine compared to animals given taurine alone. The ethanol-inducible form of cytochrome P-450 (CYP2E1) was significantly induced by alcohol; the activity was significantly lower than controls and barely detectable in animals fed the liquid alcohol diet containing taurine. In addition, alcohol significantly increased homocysteine excretion into urine throughout the 28 day period of ethanol administration; however, taurine did not prevent this increase. There was evidence of slight cholestasis in animals treated with alcohol and alcohol + taurine, as indicated by raised serum bile acids and alkaline phosphatase (ALP). The protective effects of taurine were attributed to the potential of bile acids, especially taurine conjugated bile acids (taurocholic acid) to inhibit the activity of some microsomal enzymes (CYP2E1). Thesein vivo findings demonstrate for the first time that hepatic steatosis and lipid peroxidation, occurring as a result of chronic alcohol consumption, can be ameliorated by administration of taurine to rats.