Investigation into the antioxidant role of arginine in the treatment and the protection for intralipid-induced non-alcoholic steatohepatitis

Abstract

BackgroundThis study investigated the possible roles of arginine (Arg) in ameliorating oxidative damage of intralipid (IL)-induced steatohepatitis (NASH).MethodsNASH was induced in Sprague-Dawley rats by intravenous administration of 20 % IL for three weeks and then rats were pre- and post-treated with intraperitoneal injection of Arg for two weeks. Several biochemical parameters (blood and hepatic lipid peroxidation, glutathione, glutathione peroxidase and superoxide dismutase, hepatic cytochrome P450 2El monooxygenase (CYP2E1), nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and tumor necrosis factor-α “TNF-α”) and liver histopathology were detected for rat groups.ResultsThe administration of Arg either before or after IL significantly ameliorated uncontrolled elevation of TBARS content, CYP2E1 activity (0.32 ± 0.01 or 0.3 ± 0.02 IU/mg) and TNF-α level. These effects were associated with a significant increase in the levels of glutathione, activities of antioxidant enzymes, NO level (1.649 ± 0.047 or 1.957 ± 0.073 μmol/g) and activity of hepatic eNOS (0.05 ± 0.002 or 0.056 ± 0.002 IU/mg) compared to the IL-treated rats. Moreover, the injection of Arg in NASH-induced rats showed normal hepatocytes, no steatosis and no bile duct proliferation but mild inflammation in the group which received IL after Arg.ConclusionsThese results proved that pre- and post-treatment with Arg blocked oxidative stress-induced NASH by inhibiting CYP2E1 activity, decreasing TNF- α level and restoration activities of eNOS and antioxidant enzymes as well as glutathione level. This antioxidant effect of Arg leads to reverse signs of liver pathology of NASH with amelioration of liver and kidney functions.

Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats

“…Induction of iNOS expression was associated with hepatotoxicity of other models, and its reduction was linked to hepatoprotective effect [29][30][31]. On the other hand, reduction of eNOS expression was associated with hepatotoxicity of other models, and its induction was linked to hepatoprotective effect [32][33][34]. This finding of hepatoprotective effect of nebivolol was confirmed histopathologically by improvement of diffuse liver damage occurred with APAP alone.…”

The Genetic Architecture of Diet‐Induced Hepatic Fibrosis in Mice

“…Arginine serves as a precursor not only in protein synthesis and the urea cycle but also in the generation of polyamines, creatine, and nitric oxide. Treatment with arginine appears to block oxidative stress–induced NASH by inhibiting cytochrome P450 2E1 activity, decreasing the TNF‐α level and restoring activities of endothelial nitric oxide synthase and antioxidant enzymes as well as glutathione levels . Previous studies have shown that treatment with betaine improved nonalcoholic fatty liver and associated hepatic insulin resistance in mice .…”

“…Treatment with arginine appears to block oxidative stress-induced NASH by inhibiting cytochrome P450 2E1 activity, decreasing the TNF-α level and restoring activities of endothelial nitric oxide synthase and antioxidant enzymes as well as glutathione levels. (33) Previous studies have shown that treatment with betaine improved nonalcoholic fatty liver and associated hepatic insulin resistance in mice. (34) Short-chain (C2, C3, C4, and C5) acyl derivatives of carnitine were positively correlated with fibrosis, whereas the precursor of carnitine, butyrobetaine, was inversely correlated.…”

Abnormal metabolic processes involved in the pathogenesis of non‑alcoholic fatty liver disease (Review)

“…Arginine has antioxidant effects on NASH by inhibiting cytochrome P450 family 2 subfamily E member 1 activity and by decreasing TNF-α and antioxidant enzyme concentrations ( 107 ). Dogru et al ( 108 ) reported that increased circulating asymmetric dimethylarginine may be used as an early marker for NAFLD.…”