Experiments on Wistar rats showed that feeding a ration containing 0.1% concentrate of food indoles (indole-3-carbinole and ascorbigen) for 3 weeks increased activity of phases I and II xenobiotic metabolism enzymes in the liver and intestinal mucosa and weakened the toxic effects of trichothecene T-2 mycotoxin. Activity of the key enzymes of T-2 detoxification, microsomal carboxylesterase and UDP-glucuronosyl transferase, was 1.5-2-fold higher in rats receiving T-2 toxin against the background of indole-enriched diet compared to toxin-treated rats kept on standard ration.
Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.
Male Wistar rats received a semisynthetic diet with resveratrol (100 mg/kg), indole-3-carbinol (20 mg/kg), or a mixture of these compounds in the same doses for 1 week. Activities of ethoxyresorufin dealkylase (EROD), methoxyresorufin dealkylase (MROD), pentoxyresorufin dealkylase (PROD), and 6β-testosterone hydroxylase (6β-TH) and the content of mRNA for CYP1A1, CYP1A2, and CYP3A1 were elevated in the liver of rats receiving indole-3-carbinol. These changes were accompanied by an increase in activity of phase II xenobiotic metabolism enzymes (quinone reductase, hemoxygenase-1, glutathione transferase, and UDP glucuronosyl transferase). Resveratrol did not modify activity of these enzymes. After combined treatment with the test compounds, resveratrol suppressed the indole-3-carbinol-induced increase in activities of EROD, MROD, PROD, and 6β-TH, and expression of the corresponding genes. Combined treatment was characterized by potentiation of the antioxidant effects of these compounds.
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