S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice

Abstract

PurposeTo study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model.MethodsMice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity.ResultsSAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels.ConclusionsOur results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

Myricitrin exhibits antioxidant, anti-inflammatory and antifibrotic activity in carbon tetrachloride-intoxicated mice

“…Several studies suggested that CYP2E1 was degraded during CCl 4 -induced hepatotoxicity [28,29]. Our results showed that the CCl 4 -mediated reduction in CYP2E1 expression was significantly ameliorated by myricitrin, suggesting the suppression of CYP-mediated CCl 4 bioactivation.…”

Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy

“…The development of NAFLD in rats, including the recipe and preparation protocols of diet, was performed based on our previously described voluntary oral feeding NAFLD animal model [18]. The optimum dosage of SAMC was previously shown to be effective in protecting the liver from both acute and chronic injury [19, 20]. Instead of oral administration in a dietary supplement form, SAMC was intraperitoneally injected to avoid possible degradation prior to absorption through the gastrointestinal tract (GIT).…”

“…In addition, SAMC also plays a preventive role in an acetaminophen-induced acute liver injury model through the inhibition of the activity of cytochrome P450 2E1 (CYP2E1) [18]. We previously demonstrated the protective properties of SAMC in both carbon tetrachloride-induced acute liver injury model [19] and NAFLD-induced chronic liver injury model [20]. In these studies, SAMC reduces the key events that contribute to the hepatic damage including oxidative stress, inflammation, and necrosis.…”

Garlic-derived S-allylmercaptocysteine is a hepato-protective agent in non-alcoholic fatty liver disease in vivo animal model

“…Moreover, SAMC is also shown to play antioxidative and anti-nitrosative stress roles both in vitro and in vivo [8]. The hepato-protective effect of SAMC is exhibited in an acetaminophen-induced liver injury model and a carbon tetrachloride-induced acute injury model where SAMC inhibits the activity of cytochrome P450 2E1 (CYP2E1) and reduces oxidative stress released by chemical intoxication [9–11]. However, the protective effects and underlying mechanisms of SAMC in NAFLD remain unknown.…”