Prevention Of Hepatic Disease Research Articles

Evaluation of MTBH, a novel hesperetin derivative, on the activity of hepatic cytochrome P450 isoform in vitro and in vivo using a cocktail method by HPLC-MS/MS

ABSTRACT 8-methylene-tert-butylamine-3',5,7-trihydroxy-4'-methoxyflavanone (MTBH), a novel hesperidin derivative, has potential in the prevention of hepatic disease, however, its effects on cytochrome P450 isoforms (P450s) remains unexplored. The purpose was to investigate the effects of MTBH on the mRNA, protein levels and activities of six P450s (1A2, 2C11/9, 2D2/6, 3A1/4, 2C13/19 and 2E1) in vitro and in vivo. In vitro study, rat and human liver microsomes were adopted to elucidate the inhibitory effect of MTBH on six P450s using probe drugs. In vivo study, Sprague-Dawley male rats were treated with MTBH (25, 50 or 100 mg/kg for 28 consecutive days), phenobarbital (80 mg/kg for 12 consecutive days) or 0.5% CMC-Na solution (control group) by intragastric administration, then, the mRNA, protein levels and activities of liver P450s were analyzed by real-time PCR, western blotting and probe-drug incubation systems, respectively. The in vitro study indicated that MTBH inhibits the activities of CYP3A1/4 and CYP2E1 in rat and human liver microsomes. In vivo data showed that MTBH inhibits mRNA, protein levels and activities of CYP3A1 and CYP2E1 in medium- and high-dose MTBH groups. MTBH has the potential to cause drug-drug interactions when co-administered with drugs that are metabolized by CYP3A1/4 and CYP2E1.

Antioxidant and hepatoprotective potential of endo-polysaccharides from Hericium erinaceus grown on tofu whey

Three fractions of the endo-polysaccharides from the mycelium of Hericium erinaceus (HEP) grown on tofu whey were obtained by the fractional precipitation with gradient concentrations of ethanol (HEP40, HEP60 and HEP80). The chemical and physical characteristics of the three crude polysaccharides were investigated by the combination of chemical and instrumental analysis methods. The studies to evaluate the antioxidant potential and the hepatoprotective effects of the three polysaccharides showed that they had different activities in different evaluation system. HEP80 showed strong activity on antioxidant in vitro and potent hepatoprotective effect in vivo and the hepatoprotective effect may be due to its potent antioxidant capacity. The HEP could be exploited as antioxidant product and a supplement in the prevention of hepatic diseases. The study also opens an avenue for the efficient utilization of tofu whey, which is usually discarded in environment, causing concerns.

Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride-induced oxidative stress and necroinflammation

Ethnopharmacological relevanceLycium barbarum has been used as a traditional Chinese medicine to nourish liver, kidneys and the eyes. Aim of the studyWe investigated the protective mechanisms of Wolfberry, Lycium barbarum polysaccharides (LBP) in carbon tetrachloride (CCl4)-induced acute liver injury. Materials and methodsMice were intraperitoneally injected with a 50μl/kg CCl4 to induce acute hepatotoxicity (8h) and were orally fed with LBP 2h before the CCl4 injection. There were six experimental groups of mice (n=7–8 per group), namely: control mice (vehicle only; 1mg/kg LBP or 10mg/kg LBP), CCl4-treated mice and CCl4+LBP treated mice (1mg/kg LBP or 10mg/kg LBP). ResultsPre-treatment with LBP effectively reduced the hepatic necrosis and the serum ALT level induced by CCl4 intoxication. LBP remarkably inhibited cytochrome P450 2E1 expression and restored the expression levels of antioxidant enzymes. It also decreased the level of nitric oxide metabolism and lipid peroxidation induced by CCl4. LBP attenuated hepatic inflammation via down-regulation of proinflammatory mediators and chemokines. Furthermore, LBP promoted liver regeneration after CCl4 treatment. The protective effects of LBP against hepatotoxicity were partly through the down-regulation of nuclear factor kappa-B activity. ConclusionLBP is effective in reducing necroinflammation and oxidative stress induced by a chemical toxin, thus it has a great potential use as a food supplement in the prevention of hepatic diseases.

Dietary cadmium inhibits spontaneous hepatocarcinogenesis in C3H/HeN mice and hepatitis in A/J mice, but not in C57BL/6 mice

Cadmium is known to be a potent carcinogenic and mutagenic metal. However, we demonstrated that dietary supplementation with 50 ppm cadmium inhibits spontaneous carcinogenesis in C3H/HeN and spontaneous hepatitis in A/J mice. We found that the frequencies of spontaneous hepatocarcinogenesis in C3H/HeN mice and of spontaneous hepatitis in A/J mice fed low-dose cadmium for 54 weeks were significantly lower than those in the respective control groups. A cadmium-induced increase in metallothionein production itself and/or metallothionein-associated increases in hepatic zinc concentrations may be involved in the observed preventive effects of cadmium. Our results suggest that low doses of cadmium in the diet or environment may play a beneficial role in the prevention of hepatic disease in humans and animals.