Effect of melatonin on the production of microsomal hydrogen peroxide and cytochrome P-450 content in rat treated with aflatoxin B 1

Abstract

Aflatoxin B 1 (AFB 1) is a food contaminant fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this study we went on to show the effect of melatonin as a free radical scavenger on the production of microsomal hydrogen peroxide (H 2O 2) during the metabolic activation AFB 1. The production of microsomal H 2O 2 in vitro during the metabolic activation of different chemical carcinogens has been reported previously. We also studied the effect of melatonin on the cytochrome P-450 content as a major microsomal monooxygenase isoenzymes system in rat liver responsible for the metabolic activation of AFB 1. The amounts of H 2O 2 and cytochrome P-450 contents in rat treated with melatonin (0.2 mg/kg BW) and/or AFB 1 (0.2 mg/kg BW) at various time intervals has been measured. Animals treated with melatonin exhibited markedly inhibition in the amounts of H 2O 2 after 1, 3, and 6 h. The highest level of inhibition (3.0 nmol H 2O 2/mg protein) was detected after 6 h. However, cytochrome P-450 contents were also decreased after the same period of time. The highest level of inhibition (2.1 nmol/mg protein) was detected after 3 h of injection. A pronounced augmentation of H 2O 2 production was observed in rat treated with AFB 1 only. The highest level of H 2O 2 (100 nmol/mg protein) was measured after 1 h. Cytochrome P-450 contents were also decreased in response to AFB 1 injection over the same time intervals. Contrary data was detected in animals received both AFB 1 and melatonin. The generation of H 2O 2 was inhibited by melatonin after 1, 3 and 6 h. The highest level of inhibition (44.2 nmol/mg protein) was observed after 6 h. Finally, these data suggested that melatonin as a free radical scavenger inhibited the microsomal production of H 2O 2 in rat treated with AFB 1.