The indiscriminate and rampant use of pesticides has raised serious concerns regarding their toxic impact on non-target organisms which underlines need for the development of an effective antidote. Metabolic activation of organophosphate pesticides by the phase I enzyme, cytochrome P450 plays a key role in influencing pesticide-toxicity. In this study, we have investigated the effect of environmentally relevant malathion concentration (100 μg/L) alone and in combination with vitamin B12 on the expression of genes related to xenobiotic metabolism such as CYP enzymes, PgP and the key oxidative stress responsive transcription factor, Nrf2 in zebra fish liver and brain. Expressions of Nrf2-trasncribed antioxidant genes and their activities were also measured. Administration of vitamin B12 successfully revived motor functions by modulation of AchE activity. Mechanistically, vitamin B12 was demonstrated to alleviate oxidative stress which was accompanied by decreased phase-I enzyme cyp3c1 and increased pgp expressions.
Keywords: CYP450; Malathion; PgP; oxidative stress; sub-lethal toxicity; vitamin B12; zebra fish.