Effects of L-Arabinose on Drug Metabolizing and Antioxidant Enzymes in Rat

摘要

This study was conducted to assess the effects of L-arabinose on the antioxidant and drug metabolizing enzymes in rats. Forty-eight rats were equally divided into six groups. The rats in three groups were respectively administered with 500, 1 000 and 2 000 mg/kg L-arabinose for 38 days. In blank control, L-arabinose was replaced by an equal volume of distilled water. In two positive control groups, the rats were intraperitoneally injected with 80mg/kg sodium barbital or dexamethasone for three consecutive days since the 36th day. Twenty-four hours after the last dose, blood was sampled from their femoral artery. And the activities of antioxidant enzymes and the concentration of free radicals in serum were measured. Rat liver tissues were collected and homogenized, centrifuged at 4 000 r/min and 4°C. Then, a portion of the supernatant was used for the measurement of the activities of antioxidant enzymes and the concentration of free radicals. Liver microsomes and cytoplasmic fluid were obtained by differential centrifugation. The concentration of cytochrome b_5, the activities of three phase-I metabolic enzymes NADPH-cytochrome C reductase, CYP3A, CYP2E1 and two phase-II metabolic enzymes glutathione-S-transferase (GST) and UDP-glucuronyl-transferases (UGT) were measured using double-beam UV/Vis spectrophotometry. The treatment with 2 000 mg/kg L-arabinose significantly reduced the SOD and GSH-PX activities in rat serum, the NOS activity, MDA concentration, NO concentration in liver tissue, greatly increased the GST activity in liver tissue, microsomes and cytoplasmic fluid, and greatly reduced the UGT activity in microsomes and cytoplasmic fluid. The treatment with 1 000 mg/kg L-arabinose significantly reduced the NO concentration in rat serum, and the UGT activity in microsomes and cytoplasmic fluid. The treatment with 500 mg/kg L-arabinose significantly reduced the GSH-PX activity, the NO concentration in rat serum and the NOS activity in liver tissue. L-arabinose can decrease the antioxidant capacity in rat blood and the concentration of free radicals in rat liver. L-arabinose has no adverse effect on the major drug-metabolizing enzymes in rat, but it reduces the activities of phase-II drug-metabolic enzymes GST and UGT to a certain degree, suggesting that no or slight metabolic drug-drug interactions in liver can be induced by the combined use of L-arabinose and drugs.