Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Agrimonia eupatoria protects against chronic ethanol-induced liver injury in rats

This study examined the hepatoprotective effects of Agrimonia eupatoria water extract (AE) against chronic ethanol-induced liver injury. Rats were fed a Lieber–DeCarli liquid diet for 8 weeks. Animals were treated orally with AE at 10, 30, 100, and 300 mg/kg/day. After chronic consumption of ethanol, serum aminotransferase activities and pro-inflammatory cytokines markedly increased, and those increases were attenuated by AE. The cytochrome P450 2E1 activity and lipid peroxidation increased after chronic ethanol consumption, while reduced glutathione concentration decreased. Those changes were attenuated by AE. Chronic ethanol consumption increased the levels of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 protein expression, inducible nitric oxide synthase and cyclooxygenase-2 protein and mRNA expression, and nuclear translocation of nuclear factor-kappa B, which was attenuated by AE. Our results suggest that AE ameliorates chronic ethanol-induced liver injury, and that protection is likely due to the suppression of oxidative stress and TLR-mediated inflammatory signaling.     

Hepatoprotective effects of chestnut (Castanea crenata) inner shell extract against chronic ethanol-induced oxidative stress in C57BL/6 mice

This study was carried out to evaluate the protective effects of chestnut inner shell extract (CISE) on chronic ethanol-induced oxidative stress in liver. Mice were fed a control liquid diet (Normal-control), liquid diet containing ethanol alone (EtOH + Vehicle), or were administered CISE and ethanol (EtOH + CISE) for 6 weeks. Administration of ethanol induced liver damage with significant increase of plasma GOT, GPT, hepatic triglyceride (TG) and thiobarbituric acid reactive substance (TBARS) levels. By contrast, co-treatment of CISE with ethanol significantly decreased the activities of GOT and GPT in the plasma, and hepatic TG and TBARS levels. Histological observations were consistent with the result obtained from hepatic lipid quantification. Moreover, CISE treatment with ethanol decreased CYP2E1 expression and increased activities of catalase and superoxide dismutase, which were significantly inhibited by treatment with ethanol alone. To determine the active compound of CISE, fractionation of CISE was conducted and scoparone and scopoletin were identified as main compounds. These compounds were also shown to inhibit the ethanol-induced reduction in antioxidant enzyme activity in an in vitro model system. These results suggest that CISE has protective effects against ethanol-induced oxidative damage, possibly by inhibition of lipid accumulation, peroxidation and increase of antioxidant defense system in the liver.     

Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats

The anti-fibrotic effects of a hot-water extract form the traditional Chinese medicinal herb Salvia miltiorrhiza (Labiatae) on liver fibrosis induced by biliary obstruction was studied in rats. Liver fibrosis was induced in male Sprague-Dawley rats by bile duct ligation and scission (BDL). After surgery, the hot-water extract of S. miltiorrhiza roots (100 mg kg(-1), p.o.) was administered daily for 28 days. The concentrations of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin and total cholesterol in serum and hydroxyproline and malondialdehyde contents in liver were significantly increased in BDL rats. Treatment with the extract of S. miltiorrhiza significantly reduced (P < 0.01) the serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total cholesterol concentrations in BDL rats. The liver hydroxyproline content in BDL rats treated with extract was also reduced to 68% of that in BDL control rats (P < 0.01). The liver malondialdehyde content in BDL rats treated with the extract was also reduced to 47% of that in BDL control rats (P < 0.01). The morphological characteristics of fibrotic livers were improved in BDL rats treated with extract. Immunohistochemical examination of fibrotic liver showed that the extract of S. miltiorrhiza markedly reduced protein expression of alpha-smooth muscle cell-like actin, which indicates that hepatic stellate cell activation was inhibited during liver fibrosis development. The results indicate that the hot-water extract of S. miltiorrhiza roots inhibits fibrosis and lipid peroxidation in rats with liver fibrosis induced by biliary obstruction.     

Taurine treatment reduces hepatic lipids and oxidative stress in chronically ethanol-treated rats

In this study, we evaluated whether taurine treatment has a protective effect on the prooxidant-antioxidant state following chronic ethanol treatment in rats. Rats were given water containing 20% ethanol (v/v) as drinking water for 3 months. Chronic ethanol treatment in drinking water resulted in increased oxidative stress in the liver of rats. Taurine treatment was performed by adding 1% taurine (w/v) to the drinking water plus injection (400 mg/kg body weight) intraperitoneally 3 times/week for 28 d after ethanol cessation in chronically ethanol-treatad rats. This treatment starting after ethanol cessation caused a significant decreases in serum transaminase activities and hepatic total lipid, triglyceride, malondialdehyde, and diene conjugate levels and significant increases in hepatic glutathione, vitamin E, and vitamin C levels, but did not alter the activities of superoxide dismutase, glutathione peroxidase, and glutathione transferase in the liver as compared with chronically ethanol-treated rats. Accordingly, we propose that taurine has a restorative effect on ethanol-induced hepatic damage by decreasing oxidative stress.     

Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.     

Antioxidant effect of 2-hydroxy-4-methoxy benzoic acid on ethanol-induced hepatotoxicity in rats

Alcoholic liver disease (ALD) is one of the most common diseases in society. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of ALD. 2-Hydroxy-4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India, is expected to significantly inhibit the development of liver injury in ethanol administration. It is expected to reduce the severity of liver damage in terms of body weight, hepatic marker enzymes, oxidative stress, antioxidant status and histological changes in ethanol-induced hepatotoxic rats. Hepatotoxicity was induced by administering 20% ethanol (5 g kg(-1) daily) for 60 days to male Wistar rats, which resulted in significantly decreased body weight and an increase in liver-body weight ratio. The liver marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase were elevated. In addition, the levels of plasma, erythrocyte and hepatic thiobarbituric acid reactive substances, hydroperoxides and conjugated dienes were also elevated in ethanol-fed rats as compared with those of the experimental control rats. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin C and alpha-tocopherol was also observed on alcohol administration as compared with experimental control rats. HMBA was co-administered at a dose of 200 mug kg(-1) daily for the last 30 days of the experiment to rats with alcohol-induced liver injury, which significantly increased body weight, significantly decreased the liver-body weight ratio, transaminases, alkaline phosphatase, gamma-glutamyl transpeptidase and lactate dehydrogenase, significantly decreased the levels of lipid peroxidative markers, significantly elevated the activity of enzymic and non-enzymic antioxidants in plasma, erythrocytes and liver and also increased levels of plasma and liver vitamin C and alpha-tocopherol at the end of the experimental period as compared with untreated ethanol-administered rats. The histological changes were also in correlation with the biochemical findings. The results suggest that HMBA administration may afford protection against ethanol-induced liver injury in rats.     

Hepatic mitochondrial prooxidant and antioxidant status in ethanol-induced liver injury in rats

In this study, prooxidant and antioxidant status in liver homogenates and their mitochondrial fractions were investigated in both chronic and chronic plus acute ethanol-treated rats. Increases in serum transaminase activities, as well as increases in total lipid, triglyceride, malondialdehyde (MDA) and diene conjugate (DC) levels and decreases in glutathione (GSH), vitamin E and vitamin C levels, have been observed in liver homogenates following chronic ethanol treatment (20% ethanol, v/v as drinking water for 3 months), but CuZn-superoxide dismutase (CuZnSOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities remained unchanged in postmitochondrial fractions. When an acute dose of ethanol (5 g/kg, i.p.) was given rats which had received ethanol chronically, serum transaminase activities and hepatic lipid and MDA and DC levels increased further, but GSH levels and antioxidant enzymes decreased more compared to the chronic ethanol-treated rats. There were no significant differences in the levels of MDA, DC and protein carbonyl and the activities of GSH-Px and GST in the hepatic mitochondrial fraction of rats following both chronic and chronic plus acute treatments. Mn-superoxide dismutase (MnSOD) activities increased in both groups, but mitochondrial GSH levels decreased only after chronic plus acute treatment. Therefore, we suggest that the increase in MnSOD activity may play an important role in the regulation of mitochondrial susceptibility against ethanol-induced oxidative stress.     

Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake.

In order to investigate the effect of carbohydrate intake on ethanol-induced lipid peroxidation and cytotoxicity, rats were maintained on four different test diets, a medium-carbohydrate (carbohydrate intake, 8.4 g/day/rat on average), a low-carbohydrate (carbohydrate intake, 2.8 g/day/rat on average), an ethanol-containing medium-carbohydrate (carbohydrate and an ethanol intake, 8.4 and 2.9 g/day/rat on average, respectively), and an ethanol-containing low-carbohydrate diet (2.8 and 2.9 g/day/rat on average, respectively). Ethanol and the low-carbohydrate diet each increased the liver malondialdehyde content, but the combined effect of both (ethanol-containing low-carbohydrate diet) was much more prominent than either alone. The degree of increase in malondialdehyde content almost paralleled the activity of the microsomal ethanol oxidizing system. Both the low-carbohydrate and the ethanol-containing low-carbohydrate diets decreased the liver glutathione content, but ethanol combined with the medium-carbohydrate diet had no effect on the content. Ethanol treatment increased the liver triglyceride content only when combined with the low-carbohydrate diet. The rate of NADPH-dependent microsomal malondialdehyde formation was much higher in microsomes from rats maintained on the ethanol-containing low-carbohydrate diet than in those from rats on the ethanol-containing medium-carbohydrate diet, indicating that lowered carbohydrate intake augments ethanol-induced malondialdehyde accumulation in the liver by enhancing the rate of lipid peroxidation. In addition, when incubated with red blood cells in the presence of NADPH, microsomes from rats fed the ethanol-containing low-carbohydrate diet caused marked hemolysis, which was prevented by the addition of 5 mM glutathione to the incubation system. Furthermore, addition of 50 mM ethanol to the reaction system greatly accentuated the hemolysis. These results suggest that lowered carbohydrate intake at the time of ethanol consumption potentiates ethanol cytotoxicity by enhancing ethanol-induced lipid peroxidation.     

Protective effect of Gymnema montanum against renal damage in experimental diabetic rats

Gymnema montanum Hook (Asclepiadaceae), is an endemic plant species of India, traditionally used for diabetes and its management. In this experiment, the ethanol extract of G. montanum (GLEt) at a dose of 200 mg/kg body weight was tested to evaluate its effect on renal damage in alloxan-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide (600 μg/kg body weight). The GLEt and glibenclamide were administered orally for 3 weeks and the effects on glucose, insulin, renal markers including urea, creatinine and uric acid, lipid peroxidation markers including thiobarbituric reactive substances (TBARS) and hydroperoxides and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in kidney were studied. In addition, the urinary protein profile was studied using SDS–PAGE. The results indicated that the GLEt significantly normalized the elevated blood glucose, renal markers and lipid peroxidation markers and increased antioxidant levels in diabetic kidney. The diabetic rats excreted large amount of proteins than untreated rats which was normalized during the treatment with GLEt. In conclusion, the GLEt was found to be more effective in reducing oxidative stress, thus confirming the ethnopharmacological use of G. montanum in protecting diabetes and its complications.     

Chemoprotective effects of ethanolic extract of neem leaf against MNNG-induced oxidative stress

We evaluated the modifying effects of ethanolic extract of neem leaves (Azadirachta indica A. Juss) on oxidative stress induced by the potent gastric carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in male Wistar rats. The extent of lipid peroxidation and the status of the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were used as intermediate endpoints of chemoprevention. Three different concentrations of ethanolic neem leaf extract (100, 200 and 400 mg kg(-1) body weight) were administered by intragastric intubation (i.g) for five consecutive days followed by MNNG (i.g) 1.5 h after the final administration. Enhanced lipid peroxidation was accompanied by compromised antioxidant defences in the stomach, liver and erythrocytes of MNNG-treated rats. Pretreatment with ethanolic neem leaf extract at a dose of 200 mg/kg body weight (bw) significantly lowered the concentration of lipid peroxides and increased antioxidant levels. Our results demonstrate that neem leaf exerts its chemoprotective effects on MNNG- induced oxidative stress by decreasing lipid peroxidation and enhancing the antioxidant status.     

Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models

The aim of this work was to investigate the effects of Aloe vera leaf pulp and gel extracts on the liver tissue of neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. The diabetic rats were separated into four groups and each group was given the following samples by gavage, daily for 15 d: phosphate buffered saline (PBS; diabetic control), Aloe leaf pulp extract, Aloe leaf gel extract, glibenclamide. Liver tissues were examined histologically. The markers of oxidative stress: glutathione (GSH), non-enzymatic glycosylation (NEG) and lipid peroxidation (LPO), were determined in liver tissue. Biochemical parameters for liver function: serum alkaline phosphatase (ALP), and alanine transaminase (ALP) activities, were evaluated. All parameters were also determined in healthy (non diabetic) rats for comparison. In the diabetic control group, the degenerative changes in liver tissue were remarkable, while in the diabetic groups given Aloe pulp and gel extracts and glibenclamide, the damage to the liver tissue was decreased. The increase of GSH and the decrease of NEG and LPO in liver tissues with the treatment of Aloe gel extract, is consistent with the beneficial effect of Aloe. Serum ALP and ALT activities were also decreased in the groups given Aloe gel extract. It was concluded that Aloe gel extract has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes if used in the treatment of type-II diabetes.     

吲哚-3-原醇对乙醇损伤性大鼠肝切片的保护作用

目的　采用精密肝切片技术 ,研究十字花科类蔬菜提取物吲哚 3 原醇 (I3C)对乙醇肝损伤的作用及机制。方法　制作大鼠乙醇损伤肝切片模型 ,观察不同剂量I3C对培养液中肝损伤标志酶及肝细胞浆苯胺羟化酶 (ANH)、乙醇脱氢酶 (ADH)活性的影响 ,并进行组织学检查。结果　乙醇5 0mmol·L-1作用肝切片 4h时 ,培养液谷丙转氨酶、谷草转氨酶、乳酸脱氢酶和谷胱甘肽S 转移酶活性明显升高 ,同时肝细胞浆ANH活性升高、ADH活性降低 ;加入 10 0～ 4 0 0μmol·L-1的I3C后 ,培养液中各酶活性降低的同时 ,肝细胞ANH和ADH活性恢复正常。肝切片病理学检查也证实I3C的保护作用。结论　I3C能有效拮抗乙醇所致的肝损伤 ,其机制与改变乙醇代谢途径有关。     

The influence of Sacoglottis gabonensis stem bark extract and its isolate bergenin, Nigerian alcoholic beverage additives, on the metabolic and haematological side effects of 2,4-dinitrophenyl hydrazine-induced tissue damage

This study was designed to study the influence of Sacoglottis gabonensis stem bark extract on the metabolic and cytotoxic side effects of 2,4-dinitrophenyl hydrazine (2,4-DNPH) on the brain and blood using male weaving rats as the experimental model. This was after the effect of the bark extract and bergenin, its isolate, on membrane lipid peroxidation and tissue natural antioxidant defences was reported. Lipid peroxidation was induced experimentally with a single intraperitoneal phenylhydrazine (2,4-DNPH) administration at the end of 3 days exposure to the bark extract or bergenin in drinking water. Three hours later, the brain, liver and red blood cells of the experimental animals were analysed for glucose level and the blood was analysed for selected key indices of oxidative stress: red blood cell (RBC) count haemoglobin (Hb), packed cell volume (PCV) and white blood cell (WBC) count (total and differential). The bark extract exhibited a protective action on brain glucose, significantly inhibiting the glucose-depleting action of both 2,4-DNPH and ethanol. It also inhibited the lowering action of DNPH and ethanol on PCV, RBC and Hb concentration of rat blood, but inhibited proliferation of white blood cells (total and differential). The data on the effect of bergenin, on the side effects of 2,4-DNPH experimental lipid peroxidation and on ethanol followed an essentially similar trend to those of the bark extract on brain glucose. Bergenin, similar to the bark extract, exerted a protective action on the brain tissue, though to a lesser extent, against the oxidants, 2,4-DNPH and ethanol. It is evident that aqueous ethanol extract of S. gabonensis stem bark has biological antioxidant properties against 2,4-DNPH and ethanol-induced tissue damage exerting its action on the haematological and metabolic side effects of the oxidants. By virtue of its essentially similar activity under the same conditions, bergenin appears to be the phytochemical constituent that is largely responsible for the observed action of the bark extract.     

Aqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic liver fibrosis in a rat model of bile duct ligation

Cholestatic liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins, is associated with bile acid-induced oxidative stress and lipid peroxidation. We evaluated the therapeutic or protective effect of an aqueous extract of Artemisia iwayomogi Kitamura (WAI) in a rat bile duct ligation (BDL)-induced hepatic fibrogenesis model. After BDL, rats were treated once daily with 25 or 50 mg/kg of WAI for 2 weeks. The serum bilirubin, aspartate transaminase, alanine transaminase, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group. WAI administration significantly reduced these markers and restored BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAI treatment, and these changes were paralleled by significantly suppressed gene and protein expression of fibrogenic factors, including hepatic alphasmooth muscle actin, platelet-derived growth factor, and transforming growth factor β. Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL.     

Absorption of andrographolides from Andrographis paniculata and its effect on CCl4-induced oxidative stress in rats

A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42 ± 0.09 μg/ml and 1.31 ± 0.04 μg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl₄ administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl₄ did not showed significant alteration (p > 0.05) in plasma total antioxidant status (TAS) as compare to values of control group.     

The metabolism of acetaldehyde and not acetaldehyde itself is responsible for in vivo ethanol-induced lipid peroxidation in rats

A single oral administration of ethanol (5 g/kg) to rats induced a marked increase in lipid peroxidation, in the liver and kidney within 9 hr, as assessed by malondialdehyde accumulation. The pretreatment with alcohol dehydrogenase (ADH) inhibitor, 4-methylpyrazole (1 mmol/kg) caused approximately 50% inhibition of the hepatic ADH activity and abolished this ethanol-induced lipid peroxidation. The disulfiram treatment (100 mg/kg) significantly inhibited 63% of the hepatic low Km aldehyde dehydrogenase (ALDH) but not the high Km ALDH. The cyanamide treatment (15 mg/kg) effectively decreased 83% of the low Km and 70% of the high Km ALDH in the liver. Although there was more than a 20-fold elevation of acetaldehyde levels by the inhibition of acetaldehyde metabolism with disulfiram or cyanamide, the ethanol-induced lipid peroxidation was significantly suppressed by pretreatment with these drugs. More than 90% inhibition of xanthine oxidase and dehydrogenase by the pretreatment with allopurinol (100 mg/kg), with no effect on the hepatic ADH and ALDH activities, did not alter the enhancement of lipid peroxidation following ethanol administration. We propose that the metabolism of acetaldehyde (probably via the low Km ALDH) and not acetaldehyde itself is responsible for the ethanol-induced lipid peroxidation in vivo and that the contribution of xanthine oxidase, as an initiator of lipid peroxidation through acetaldehyde oxidation is minute during acute intoxication.     

Protective effect of aqueous extract of Perilla frutescens on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in rats.

The leaves of perilla [Perilla frutescens (L.) Britt. var. japonica (Hassk.) Hara] are often used in Asian gourmet food. The object of this study was to evaluate the protective effects of an aqueous extract of perilla leaves on the tert-butyl hydroperoxide (t-BHP)-induced oxidative injury observed in rat livers. The treatment of the hepatocytes with the perilla leaf extract (PLE) significantly reversed the t-BHP-induced cell cytotoxicity and lipid peroxidation. In addition, PLE exhibited ferric-reducing antioxidant power and 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activities. The in vivo study showed that the pretreatment with PLE (1000 or 3000 mg/kg) for 5 days before a single dose of t-BHP (i.p.; 0.2 mmol/kg) significantly lowered the serum levels of aspartate aminotransferase and alanine aminotransferase, reduced the indicators of oxidative stress in the liver, such as the glutathione disulfide content and lipid peroxidation level in a dose-dependent manner, and remarkably increased the activity of hepatic gamma-glutamylcysteine synthetase. Histopathological examination of the rat livers showed that PLE reduced the incidence of liver lesions induced by t-BHP. Based on the results described above, it is suggested that PLE has the potential to protect liver against t-BHP-induced hepatic damage in rats.     

Influence of naringenin on oxytetracycline mediated oxidative damage in rat liver

Naringenin is a naturally occurring citrus flavanone, which has been reported to have a wide range of pharmacological properties. The present work was carried out to evaluate the effect of naringenin on antioxidant and lipid peroxidation status in liver of oxytetracycline-intoxicated rats. Intraperitonial administration of oxytetracycline 200 mg/kg for 15 days resulted a significant elevation in serum hepatospecific markers such as aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and bilirubin and the levels of lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) in liver. Oxytetracycline also caused a significant reduction in the activities of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione (GSH), vitamin C and vitamin E in liver. Oral administration of naringenin (50 mg/kg b.w.t.) with oxytetracycline significantly decreased the activities of serum aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and the levels of bilirubin along with significant decrease in the levels of lipid peroxidation markers in the liver. In addition, naringenin significantly increased the activities of superoxide dismutase, catalase and GSH peroxidase as well as the level of GSH, vitamin C and vitamin E in liver of the oxytetracycline-treated rats. Our results demonstrate that naringenin exhibited antioxidant property and decrease the lipid peroxidation against oxytetracycline-induced oxidative stress in liver.     

PI3K/Akt pathway activation was involved in acute ethanol-induced fatty liver in mice

Accumulating evidences support the important roles of sterol regulatory element-binding protein-1 (SREBP-1) activation in ethanol-induced fatty liver, but the underlying mechanisms for its activation are not fully understood. Recent studies have demonstrated that phosphatidylinositol 3 kinase (PI3K)/Akt pathway activation could enhance SREBP-1 activity. The current study was designed to investigate the potential roles of PI3K/Akt pathway in acute ethanol-induced fatty liver in mice. In the first experiment, mice were treated with ethanol (2.5 or 5 g/kg bw) or isocaloric/isovolumetric maltose-dextrin solution, and sacrificed at several time points after ethanol exposure. As expected, ethanol dose-dependently increased the hepatic triglyceride (TG) levels and the protein levels of the mature form of SREBP-1 (n-SREBP-1). The phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β) was significantly increased in mice treated with ethanol (5 g/kg bw), while the protein levels of PI3K-p85 were significantly reduced. To confirm the roles of PI3K/Akt pathway, mice were then pretreated with wortmannin (0.7 or 1.4 mg/kg bw), a specific PI3K/Akt pathway inhibitor, before exposure to ethanol. Interestingly, a dual effect of wortmannin was observed. Low dose of wortmannin significantly reduced the hepatic TG levels, while high dose of wortmannin aggravated ethanol-induced fatty liver. The ratio of LC3II/LC3I of wortmannin (1.4 mg/kg bw) group mice was significantly increased, while the p62 protein level was significantly decreased compared to those of ethanol group, which indicated that wortmannin (1.4 mg/kg bw) might suppress the lipid degradation by autophagy. These results supported the hypothesis that PI3K/Akt activation might be involved in acute ethanol-induced fatty liver, and PI3K/Akt inhibitors might have therapeutic potential for the treatment of ethanol-induced fatty liver.