Jain Anshu, Flora S J S
Division of Pharmacology and Toxicology, Defence Research and Development, Establishment, Jhansi Road, Gwalior-474 002, India.
J Environ Biol. 2012 Mar;33(2):233-8.
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 1.17 to 1.41 microM ml(-1) in young rats and from 1.13 to 1.40 microM 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 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(-1) mg(-1) protein) and old rats (1.81 units min(-1) mg(-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(-1) mg(-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.
尼古丁会影响多种细胞过程，从基因表达的诱导到激素分泌以及酶活性的调节。本研究的目的是研究尼古丁对年轻、成年和老年大鼠氧化应激的剂量依赖性毒性，这些大鼠腹腔注射0.75、3和6 mg kg⁻¹的尼古丁（以酒石酸氢尼古丁形式），持续7天。在最低剂量的尼古丁作用下，任何年龄组的血液过氧化氢酶（CAT）活性和血液活性氧（ROS）水平均未观察到变化。然而，在最高剂量（6 mg kg⁻¹尼古丁）时，年轻大鼠的ROS水平从1.17显著增加至1.41 μM ml⁻¹，老年大鼠从1.13增加至1.40 μM ml⁻¹。然而，成年大鼠的血液ROS水平未观察到变化。给予3 mg kg⁻¹尼古丁导致所有年龄组大鼠的还原型谷胱甘肽（GSH）水平升高。年轻动物最为敏感，因为6 mg kg⁻¹的剂量导致还原型GSH水平降至0.89 mg ml⁻¹，而正常对照组为（1.03 mg ml⁻¹）。抗氧化酶超氧化物歧化酶（SOD）和CAT对6 mg kg⁻¹的剂量敏感，因为这导致所有年龄组动物的酶活性下降。此外，给予较低剂量3 mg kg⁻¹的尼古丁会使老年大鼠的SOD活性从每分钟1.48单位mg⁻¹蛋白降至1.20单位mg⁻¹蛋白。在3 mg kg⁻¹的剂量下，过氧化氢酶活性呈现类似趋势。给予尼古丁还会使年轻和老年大鼠在所有三个剂量下的血液脂质过氧化水平呈剂量依赖性增加。在所有三个年龄组中，3和6 mg kg⁻¹剂量的尼古丁暴露也会使大脑中的ROS增加。高剂量尼古丁（6 mg kg⁻¹体重）会使成年大鼠（4.27 mg g⁻¹）和老年大鼠（3.68 mg g⁻¹）的大脑GSH显著降低，但在年轻大鼠中，较低剂量（0.75 mg kg尼古丁）时水平升高至4.40 mg g⁻¹。与各自的正常对照组相比，年轻和老年大鼠在所有三个尼古丁剂量下的大脑脂质过氧化均增加。与各自的正常水平相比，在6 mg kg⁻¹的剂量下，年轻大鼠（每分钟2.88单位mg⁻¹蛋白）和老年大鼠（每分钟1.81单位mg⁻¹蛋白）的SOD活性显著增加。有趣的是，与正常对照组相比，成年大鼠的SOD活性降低（每分钟2.18单位mg⁻¹蛋白）。在年轻和老年大鼠中，3 mg kg⁻¹和6 mg kg⁻¹尼古丁剂量下过氧化氢酶活性降低，但在任何剂量下成年大鼠均未观察到影响。成年和老年大鼠的乙酰胆碱酯酶（AchE）活性呈剂量依赖性降低。总体而言，研究结果表明，与成年大鼠相比，年轻和老年大鼠对尼古丁诱导的氧化应激更为敏感。
