Title:Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism
Volume: 20
Issue: 14
Author(s): Basu Dev Banerjee*, Ranjeet Kumar, Krishna Latha Thamineni, Harendra Shah, Gaurav Kumar Thakur and Tusha Sharma
Affiliation:
- Environmental Biochemistry and Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences and GTB Hospital (University of Delhi), Dilshad Garden, Delhi-110095,India
Keywords:
Environmental pollutants, xenobiotics, drug metabolism, Phase I and II metabolizing genes, pharmacogenomics, pesticides.
Abstract:
Background: Pesticides are major xenobiotic compounds and environmental pollutants, which are able to
alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome
project, genetic variations (polymorphism) become an integral part of drug development due to their influence
on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of
active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and
pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions
collectively.
Objective: To review all the evidence concerning the effect of environmental exposure on drug metabolism with
reference to pharmacogenomics.
Methods: Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics
studies were undertaken to evaluate the influence of environmental contaminants on drug metabolism.
Results: Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under
the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism
of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters disease susceptibility as well
as the progression of disease under the influence of various environmental contaminants at various levels.
Conclusion: Individual specific drug response may be attributed to a large variety of factors alone or in combination
ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body
size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to
toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).