Vitamin B12 alleviates malathion-induced toxicity in zebra fish by regulating cytochrome P450 and PgP expressions

Abstract

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:

• Malathion
• sub-lethal toxicity
• oxidative stress
• zebra fish
• vitamin B12
• PgP
• CYP450

Acknowledgements

The research leading to these results received funding from Science and Engineering Research Board, Government of India (CRG/2019/004019). DBT‐Boost (and Ref: 49 (11)/BT (Estt)/1P-4/2013 (Part-1)), DST‐FIST (SR/FST/LSI‐585/2014 (C) dated 28th December 2015) New Delhi, Govt. of India and West Bengal State University provided instrumental and administrative support, respectively.

Author contributions

Grant acquisition: Shamee Bhattacharjee, Deba Prasad Mandal; Project administration: Shamee Bhattacharjee, Deba Prasad Mandal; Conceptualization: Shamee Bhattacharjee, Deba Prasad Mandal and Subrata Karmakar; Methodology and experimentation: Subrata Karmakar, Poulami Sengupta, Arnab Sarkar, Ashikur Rahaman; Data analysis: Shamee Bhattacharjee, Deba Prasad Mandal and Subrata Karmakar; Figures: Subrata Karmakar, Poulami Sengupta, Sonali Bhattacharya, Ashikur Rahaman and Deba Prasad Mandal; writing the original draft: Shamee Bhattacharjee and Subrata Karmakar; Manuscript editing: Shamee Bhattacharjee.

Disclosure statement

No potential conflict of interest was reported by the author(s).