Similarities in lindane induced alteration in cytochrome P450s and associated signaling events in peripheral blood lymphocytes and brain.

Abstract

Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15 mg/kg/body weight) of lindane daily for 4 days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21 days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals.

• Authors: Anwar Jamal Khan, Amit Sharma, K Dinesh, Devendra Parmar
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 60 Pg. 318-27 (Oct 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23927878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Insecticides
• RNA, Messenger
• Hexachlorocyclohexane
• Cytochrome P-450 Enzyme System
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Brain (drug effects, metabolism)
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• Dose-Response Relationship, Drug
• Hexachlorocyclohexane (toxicity)
• Insecticides (toxicity)
• Lymphocytes (drug effects, metabolism)
• Male
• Microsomes (drug effects, metabolism)
• Mitogen-Activated Protein Kinases (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Signal Transduction