Hepatic Protective Effects Research Articles

Hepatic antioxidative potential of ethyl acetate fraction of Cynodon dactylon in Balb/c mice

A study was undertaken to evaluate the antioxidative potential of ethyl acetate fraction ofCynodon dactylon in Balb/c mice. In this present study mice were divided into the two groups and each group containing 6 mice. Group I mice were orally administered with 70 µl of DMSO and are the vehicle control for ethyl acetate fraction. Group II mice were injected with ED50 70 µl of ethyl acetate fraction of C. dactylon. The activity of enzymic antioxidants (U/ mg of protein) such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were found to be significantly high in ethyl acetate fraction treated mice when compared to the control mice. The levels (g liver tissue) of nonenzymic antioxidants such as vitamin A, vitamin C, vitamin E and reduced glutathione in the ethyl acetate fraction treated mice (Vitamin A 158.224 μg, Vitamin C 7.442 μg, Vitamin E 5.383 μg and reduced GSH 489.283 nmoles) was found to be significantly higher than that found in control mice. These results suggest that ethyl acetate fraction of C. dactylon has very good antioxidant and hepatic protective effect of normal oxidative stress in Balb/c mice. Currently, the importance of oxidative stress in the patho physiology of many human disorders has been highlighted, thus use of this plant as an herbal medicine is highly recommended. Hereafter, trials to establish efficacy and optimum dosage of the present herbal product for treating human chronic diseases with pathophysiology of oxidative stress are essential. Key words: Cynodon dactylon, antioxidants, Balb/c mice, ethyl acetate fraction.

Sphinganine-1-phosphate protects kidney and liver after hepatic ischemia and reperfusion in mice through S1P1 receptor activation

Liver failure due to ischemia and reperfusion (IR) and subsequent acute kidney injury are significant clinical problems. We showed previously that liver IR selectively reduced plasma sphinganine-1-phosphate levels without affecting sphingosine-1-phosphate (S1P) levels. Furthermore, exogenous sphinganine-1-phosphate protected against both liver and kidney injury induced by liver IR. In this study, we elucidated the signaling mechanisms of sphinganine-1-phosphate-mediated renal and hepatic protection. A selective S1P1 receptor antagonist blocked the hepatic and renal protective effects of sphinganine-1-phosphate, whereas a selective S1P2 or S1P3 receptor antagonist was without effect. Moreover, a selective S1P1 receptor agonist, SEW-2871, provided similar degree of liver and kidney protection compared with sphinganine-1-phosphate. Furthermore, in vivo gene knockdown of S1P1 receptors with small interfering RNA abolished the hepatic and renal protective effects of sphinganine-1-phosphate. In contrast to sphinganine-1-phosphate, S1P's hepatic protection was enhanced with an S1P3 receptor antagonist. Inhibition of extracellular signal-regulated kinase, Akt or pertussis toxin-sensitive G-proteins blocked sphinganine-1-phosphate-mediated liver and kidney protection in vivo. Taken together, our results show that sphinganine-1-phosphate provided renal and hepatic protection after liver IR injury in mice through selective activation of S1P1 receptors and pertussis toxin-sensitive G-proteins with subsequent activation of ERK and Akt.

Antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in rats fed a high fat diet

BackgroundNelumbo nucifera, known as sacred lotus, is a well-known medicinal plant and this lotus root is commonly used as food compared to different parts of this plant. This study was conducted to investigate the antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in high fat diet-induced obese rats.MethodsThirty-two male Sprague-Dawley rats (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus root hot water extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT group). Lotus root hot water extract was orally administrated (400mg/kg/day) to HFR and HFRT groups and the same amount of distilled water was orally administered to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v).ResultsThe activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups compared to HF group. Thiobarbituric acid reactive substance contents in all groups fed a high fat diet were higher compared to N group. The activities of hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF group.ConclusionsThese results suggest that lotus root hot water extract with taurine supplementation shows antioxidant and hepatic protective effects in high fat diet-induced obese rats.

Adiponectin: A Differential Marker Between Steatosis and Steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) becoming a world - wide public health problem.It represents a spectrum of disease ranging from simple steatosis to steatohepatitis (NASH). Adipocytokines refer to adipocyte-derived biologically active molecules TNF-α, leptin and adiponectin, all been implicated in development of hepatic inflammation and fibrosis in NAFLD patients. This new hormone differ from its predecssors in important feature, production and concentration acutully decrease in obesity, and all adipose-derived hormone are increased. It is possible that adiponectin expression is activated during adipogenesis, a feed back inhibition on its production may occur during the development of obesity. Adiponectin may exert a hepatic protective effect. Objective: Was to evaluate adiponectin level as a differential marker between steatosis and Steatohepatitis. Methods: Twenty NAFLD patients, twenty biopsy proved NASH and twenty control subjects, matched for age,sex and BMI.All the subjects were subjected to an abdominal ultrasonography, routine biochemical evaluation: liver function ALT& AST, lipid profile (cholesterol, triglycerides, HDL-C), CRP& Adipocytokines (TNF-α, IL-6, LEPTIN, & Adiponectin). Results: Plasma adiponectin levels were significantly lower in NAFLD patients than control gp (6.15± 1.39ng/ml vs12.03±3.46ng/ml). Adiponctin was significantly lower in NASH than NAFLD (1.80 0±0.96 ng/ml vs 6.15±1.39 ng/ml). leptin level was significantly higher in NAFLD than NASHgp (69.50±18.70ng/ml vs 43.20±6.93ng/ml). adiponectin ROC curve showed an AUROC curve in NAFLD gp (o.945 p=0.049) while inNASH was(0.995 p=0.007).TNF-α & IL-6 was significantly higher in NASH than NAFLD gp (79.25±13.89 pg/ml vs41.25±17.53 pg/ml)and (110.20±55.34 pg/ml vs 43.85±16.13). Plasma adiponectin level in NAFLD gp was inversely correlated with T.G (r=-0.368 p=0.111). GOT (r=-0.037 p=0.878) & GPT (r=-0.022 p=0.926) while it was +ve correlated in NASH gp with Cholesterol (r=0.317 p=0.174) & T.G (r=0.042 p=0.861). Conclusion: This data support a role for low circulating adiponectin in the pathogenisis of NAFLD and hypoadiponectinemia found to be a feature of NASH. ADIPONECTIN found to be a non –invasive differential marker between NAFLD & NASH.

The protective effect of Zizyphus jujube fruit on carbon tetrachloride-induced hepatic injury in mice by anti-oxidative activities

Aim of the study The study was aimed to investigate the protective effect against hepatic injury induced by CCl 4 for the ethanolic extract of FZJ. Materials and methods The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected as biomarker in blood of hepatic injury. Product of lipid peroxidation (MDA), activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed at the degree of hepatic injury. Results After administrated the FZJ, the dose of 200 mg/kg significantly decreased ALT and AST, and attenuated histopathology of hepatic injury, and ameliorated the oxidative stress in hepatic tissue. Partly assayed indexes were ameliorated after administrated FZJ at the dose of 100 mg/kg. Conclusion These results indicated that hepatic protective effects of FZJ were very relevant to modulate the oxidative stress in hepatic injury.

Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats

Momordica charantia L. (MC) (Cucurbitaceae) commonly known as balsam pear, bitter gourd or karela, used in several purposes in traditional medicine is an important medicinal plant. Two sets of experiments were carried out, the first experiment indicated that the LD 50 for MC juice and alcoholic extracts were 91.9 and 362.34 mg/100 g b.wt., respectively, of subcutaneously “s.c.” injected mice. The toxic signs were recorded within the first 24 h post-injection. The second experiment was performed to evaluate the effect of MC juice and alcoholic extracts on blood glucose and other biochemical parameters in normal and diabetic rats. Both extracts induced a significant decrease in serum glucose levels in normal and diabetic rats. The two extracts did not show any significant effect in urea, creatinine, ALT, AST and AP in normal rat, while in diabetic rats the two extracts caused a significant decrease in serum urea, creatinine, ALT, AST, AP, cholesterol and triglyceride levels. Also, these results suggested that MC extracts possesses anti-diabetic, hepato-renal protective and hypolipidemic effect in alloxan-induced diabetic rats. Thus, MC is alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus.

Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning.

To investigate the role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning (IPC). A rat model of acute hepatic ischemia-reperfusion was established, 24 healthy male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group. IPC was achieved by several brief pre-reperfusions followed by a persistent reperfusion. Concentration of malondialdehyde (MDA) and activity of several antioxidant enzymes in hepatic tissue were measured respectively. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and expression of Bcl-2 protein was measured by immunohistochemical techniques. Moreover, mitochondrial ultrastructure and parameters of morphology of the above groups were observed by electron microscope. Compared with IR group, the concentration of MDA and the hepatocellular apoptotic index in IPC group was significantly reduced (P<0.05), while the activity of antioxidant enzymes and OD value of Bcl-2 protein were markedly enhanced (P<0.05). Moreover, the injury of mitochondrial ultrastructure in IPC group was also obviously relieved. IPC can depress the synthesis of oxygen free radicals to protect the mitochondrial ultrastructure and increase the expression of Bcl-2 protein that lies across the mitochondrial membrane. Consequently, IPC can reduce hepatocellular apoptosis after reperfusion and has a protective effect on hepatic ischemia-reperfusion injury.

Epidermal Growth Factor Protects the Liver Against Alcohol‐Induced Injury and Sensitization to Bacterial Lipopolysaccharide

Whereas the role of proinflammatory cytokines in the pathogenesis of alcoholic liver disease has been at the forefront of investigation, a possible role for anti-inflammatory cytokines in this disease has received little attention. This study investigated (1) the hepatic protective effect of an anti-inflammatory cytokine, epidermal growth factor (EGF), against deleterious effects of alcohol and sensitization to bacterial lipopolysaccharide (LPS), and (2) the possible mechanisms that underlie such protection. Male C57BL/6 mice were fed a Lieber-DeCarli liquid diet that contained alcohol or an isocaloric replacement for 6 weeks. The animals then were treated daily with human EGF for 7 days (5 microg/mouse), after which they were injected with either LPS (1 mg/kg of body weight) or vehicle and killed 8 hr later. Blood and liver were analyzed for plasma aminotransferase activity, liver histology, liver apoptotic nuclei, mRNA of several cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-10), apoptotic ligands (TRAIL), cytokine receptors (TNFRp55), pro- and antiapoptotic regulators/adaptors (Fas receptor, FasL, FADD, TRADD, RIP, Bak, Bax, Bcl-X, Bcl-2 and Bcl-w), and caspase-8. Alcohol increased plasma aminotransferase activity and sensitized the liver to the effects of LPS, such as polymorphonuclear infiltration, occurrence of necrotic foci and microabscesses, and increased apoptosis. These changes were associated with elevated mRNA expression of proapoptotic regulators/adaptors. EGF either counteracted or markedly blunted most of these effects. EGF did not affect liver mRNA expression of TNF-alpha, IL-1beta, IL-6, and IL-10, which suggested that these cytokines were not involved in EGF protective effect. EGF protection was mediated by down-regulation of apoptosis through suppression of proapoptotic gene expression. EGF protects the liver against both alcohol-induced liver damage and liver sensitization to bacterial LPS through down-regulation of apoptosis.

The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (II).

Four crude drug extracts of Solanum incanum (entire plant), Ixeris chinensis (entire plant), Gardenia jasminoides (wild and cultivated, fructus) were administered to rats as dose of 1.0 g/kg, I.P. injection to screen the liver protective effect on CC14 induced hepatotoxicity. The acute increase of transaminase SGOT and SGPT levels that was caused by CC14 (1.0 ml/kg) S.C. injection can be significantly improved when treated with Solanum incanum (p less than 0.005), Ixeris chinensis (p less than 0.001), Gardenia jasminoides (cultivated) (p less than 0.005) but only a moderate change was shown by means of wild Gardenia jasminoides (p less than 0.05). As our results indicated, the extraction of these drugs has been found to possess a marked hepatic protective effect. The hepatic fatty metamorphosis and necrosis of central lobule were obviously improved by S. incanum and I. chinensis, administration, while the effect of treatment with G. jasminoides (cultivated) demonstrated a moderate protective action and little histopathological change by G. jasminoides (wild). In contrast to B. chinese, which has been reported previously as a treatment criteria, the S. incanum (p less than 0.01) and I. chinensis (p less than 0.01) in the present study have indicated that a significantly different hepatic protective effect on CC14 induced hepatic injury.

The pharmacological and pathological studies on several hepatic protective crude drugs from Taiwan (I).

This study is to investigate the hepatic protective effect of several Taiwan crude drug extractions on the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The pharmacological and pathological effects of Bupleurum chinense, Phellodendron wilsonii, Clematis chinensis and Hedyotis corymbosa were analyzed by liver enzyme function test and pathological studies. However, the results of amine transferase SGOT and SGPT have shown a significant hepatic protective effect after treatment with Bupleurum chinense (P less than 0.005), Phellodendron wilsonii (P less than 0.001), Clematis chinensis (P less than 0.005) and Hedyotis corymbosa (P less than 0.005, SGPT only). The fatty degeneration around the central vein area and necrosis of the central lobule can be significantly improved by P. wilsonii and moderately changed by B. chinense or C. chinensis. Although fatty metamorphosis has been affected by H. corymbosa, various inflammatory cell infiltrations in the cytoplasm were noted.