Prevalence of CYP2C8 polymorphisms in a North Indian population.

CYP2C8 is an important member of the cytochrome P450 family of enzymes; it affects the activity of various drugs used in routine clinical practice, including amiodarone, chloroquine, amodiaquine, and repaglinide, as well as endogenous compounds, such as arachidonic acid and retonic acid. It is also the main enzyme involved in the metabolism of the widely used anticancer drug Paclitaxel, which has a very narrow therapeutic index. There is evidence that single nucleotide polymorphisms in the CYP2C8 gene influence the adverse reactions and/or the efficacy of drugs metabolized by this enzyme. We examined the allele and genotype frequencies of widely studied functional polymorphisms of the CYP2C8 gene in a North Indian population. We assayed the genomic DNA of at least 251 healthy unrelated North Indians for CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 genetic polymorphisms by RFLP technique. These results were compared to information on other populations. The allelic frequencies of CYP2C8*2, CYP2C8*3, and CYP2C8*4 were found to be 3, 4, and 4% respectively. The two CYP2C8*3 polymorphisms (G416A and A1196G) were found to be completely linked to each other. Allele frequencies of CYP2C8 genetic variants in northern Indians were found to have a distinct pattern that differs from that of southern Indian and other global populations. This is the first report from North India on CYP2C8 polymorphisms. Ethnic differences with respect to polymorphisms are the molecular basis of interethnic variability in pharmacokinetics. Our study may help in rational use of drugs that are substrates for CYP2C8 in this population.

Premature coronary artery disease and familial hypercholesterolemia: need for early diagnosis and cascade screening in the Indian population.

Cardiovascular disease (CVD) is the leading cause of death in India, accounting for 28% of mortality. The average age of onset of CVD is younger (below 55 years) among Indians than in other populations. This may be due to bad lifestyle, genetic factors, or both. Hypertension, smoking, diabetes, and physical inactivity have been identified as modifiable risk factors for heart disease. Hypercholesterolemia is the most common and treatable cause of heart disease. Genetic factors that lead to hypercholesterolemia have not been fully studied in India. Familial Hypercholesterolemia results from mutations in the LDL receptor, ApoB, PCSK9, and ApoE genes. There is an urgent need to screen subjects with premature CAD and their relatives in India for the presence of FH, identify the mutations that lead to high cholesterol, and carry out cascade screening in the at-risk relatives. Those harbouring mutations in the above genes can be treated to lower the cholesterol levels, prevent early CVD, and avoid death. A programme based on these lines has been initiated in Delhi.

Phytotoxicity of volatile oil from Eucalyptus citriodora against some weedy species.

A study was undertaken to explore the phytotoxicity of volatile essential oil from Eucalyptus citriodora Hook. against some weeds viz. Bidens pilosa, Amaranthus viridis, Rumex nepalensis, and Leucaena leucocephala in order to assess its herbicidal activity. Dose-response studies conducted under laboratory conditions revealed that eucalypt oils (in concentration ranging from 0.0012 to 0.06%) greatly suppress the germination and seedling height of test weeds. At 0.06% eucalypt oil concentration, none of the seed of test weeds germinated. Among the weed species tested, A. viridis was found to be the most sensitive and its germination was completed inhibited even at 0.03%. Not only the germination and seedling growth, even the chlorophyll content and respiratory activity in leaves of emerged seedlings were severely affected. In A. viridis chlorophyll content and respiratory activity were reduced by over 51% and 71%, respectively, even at a very low concentration of 0.06%. These results indicated an adverse effect of eucalypt oils on the photosynthetic and energy metabolism of the test weeds. A strong negative correlation was observed between the observed effect and the concentration of eucalypt oil. Based on the study, it can be concluded that oil from E. citriodora possess strong inhibitory potential against weeds that could be exploited for weed management.

2-Benzoxazolinone (BOA) induced oxidative stress, lipid peroxidation and changes in some antioxidant enzyme activities in mung bean (Phaseolus aureus).

2-Benzoxazolinone (BOA), a well-known allelochemical with strong phytotoxicity, is a potential herbicidal candidate. The aim of the present study was to determine whether phytotoxicity of BOA is due to induction of oxidative stress caused by generation of reactive oxygen species (ROS) and the changes in levels of antioxidant enzymes induced in response to BOA. Effect of BOA was studied on electrolyte leakage, lipid peroxidation (LP), hydrogen peroxide (H(2)O(2)) generation, proline (PRO) accumulation, and activities of antioxidant enzymes-superoxide dismutase (SOD, 1.15.1.1), ascorbate peroxidase (APX, 1.11.1.11), guaiacol peroxidase (GPX, 1.11.1.7), catalase (CAT, 1.11.1.6) and glutathione reductase (GR, 1.6.4.2) in Phaseolus aureus (mung bean). BOA significantly enhanced malondialdehyde (MDA) content, a product of LP, in both leaves and roots of mung bean. The amount of H(2)O(2), a product of oxidative stress, and endogenous PRO increased many-fold in response to BOA. Accumulation of PRO, MDA and H(2)O(2) indicates the cellular damage in the target tissue caused by ROS generated by BOA. In response to BOA, there was a significant increase in the activities of scavenging enzymes SOD, APX, GPX, CAT, and GR in root and leaf tissue of mung bean. At 5 mM BOA, GR activity in roots showed a nearly 22-fold increase over that in control. The present study concludes that BOA induces oxidative stress in mung bean through generation of ROS and upregulation of activities of various scavenging enzymes.