Dose related effects of nicotine on oxidative injury in young, adult and old rats.

ABSTRACT

Nicotine affects a variety of cellular process ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of the present study was to study the dose dependent toxicity of nicotine on the oxidative stress in young, adult and old rats which were administered 0.75, 3 and 6 mg kg-1 nicotine as nicotine hydrogen tartarate intraperitoneally for a period of seven days. No changes were observed in blood catalase (CAT) activity and level of blood reactive oxygen species (ROS) in any of the age group at the lowest dose of nicotine. However, at the highest dose (6 mg kg-1 nicotine) ROS level increased significantly from 1.17to 1.41>M ml-1 in young rats and from 1.13 to 1.40 >M ml-1 in old rats. However, no change was observed in blood ROS levels of adult rats. Administration of 3 mg kg-1 nicotine resulted in an increase in level of reduced glutathione (GSH) in rats of all the age groups. The young animals were the most sensitive as a dose of 6 mg kg-1 resulted in decline in the levels of reduced GSH to 0.89 mg ml-1 as compared to normal control (1.03 mg ml-1). The antioxidant enzymes SOD and CAT were sensitive to a dose of 6 mg kg-1 as it resulted in decline of the enzymatic activity in all age group animals. Also, administration of nicotine at a lower dose of 3 mg kg-1 inhibited SOD activity from 1.48 to 1.20 units min-1 mg-1 protein in old rats. Catalase activity showed a similar trend at a dose of 3 mg kg-1. Administration of nicotine also increased the blood lipid peroxidation levels at all three doses in young and old rats dose dependently. Nicotine exposure also increased ROS in brain at the doses of 3 and 6 mg kg-1 in all the three age groups. Brain GSH decreased significantly at high dose of nicotine (6 mg kg-1 b.wt.) in adult rats (4.27 mg g-1) and old rats (3.68 mg g-1) but in young rats level increased to 4.40 mg g-1 at the lower dose (0.75 mg kg-1 nicotine). Brain lipid peroxidation increased at all three doses of nicotine in young as well as old rats as compared to their respective normal control. The SOD activity increased significantly in young (2.88 units min-1mg-1 protein) and old rats (1.81 units min-1mg-1 protein) as compared to their respective normal at a dose of 6 mg kg-1. Interestingly, the SOD activity decreased in adult rats (2.18 units min-1mg-1 protein) as compared to its normal control. Catalase activity decreased at the dose of 3 mg kg-1 and 6 mg kg-1 nicotine in young and old rats but no effect was observed in adult rats at any of the doses. Acetylcholine esterase (AchE) activity decreased in a dose dependent manner in adult and old rats. Overall, the results of the study indicate that young and old rats are more sensitive to nicotine induced oxidative stress as compared to the adult ones.