Parthasarathy Narayanaperumal Jeya, Kumar Ramasundaram Sri, Manikandan Sundaramahalingam, Narayanan Govindarajulu Sathya, Kumar Raman Vijaya, Devi Rathinasamy Sheela
Immunology Laboratory, Department of Physiology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.
Chem Biol Interact. 2006 May 15;161(1):14-25. doi: 10.1016/j.cbi.2006.02.005. Epub 2006 Mar 6.
It is well known that the nervous system has increased susceptibility to methanol intoxication. The present study reveals the effect of methanol intoxication on antioxidant status, lipid peroxidation and DNA integrity in hypothalamic-pituitary-adrenal (HPA) axis organs and spleen. Non-specific and specific immune functions were analyzed. In addition, open field behavior, plasma corticosterone level and blood methanol level were estimated. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.wt., i.p.) for 1 day, 15 and 30 days. Administration of methanol showed significant increase in enzymatic (superoxide dismutase, catalase, glutathione peroxidase), non-enzymatic (reduced glutathione and Vitamin C) antioxidants and lipid peroxidation (LPO) in hypothalamus and adrenal gland of day 1 group. However, decrease in enzymatic and non-enzymatic antioxidants with concomitant increase in LPO level were observed in 15 and 30 days groups. Plasma corticosterone level was significantly increased in day 1 and 15 days groups whereas, 30 days methanol intoxication group showed considerable decrease in corticosterone level compared with control animals. Cell-mediated immune response of footpad thickness was significantly decreased with an increased leukocyte migration inhibition. Humoral immune response of antibody titers was elevated in methanol-intoxicated groups. Neutrophil functions, adherence and phagocytic index (PI) were found to be significantly decreases. Furthermore, significant increase in the avidity index and nitro blue tetrozolium reduction was observed in the methanol exposed animals. Day 1 methanol exposed group showed increased PI compared to the control ones. Methanol exposure for 30 days showed an increased DNA fragmentation in the hypothalamus, adrenal glands, and spleen. In conclusion, exposure to methanol-induced oxidative stress disturbs the HPA-axis function altering the level of corticosterone, which lead to varied non-specific and specific immune response in experimental rats.
众所周知,神经系统对甲醇中毒的易感性增加。本研究揭示了甲醇中毒对下丘脑 - 垂体 - 肾上腺(HPA)轴器官和脾脏中抗氧化状态、脂质过氧化和DNA完整性的影响。分析了非特异性和特异性免疫功能。此外,还评估了旷场行为、血浆皮质酮水平和血液甲醇水平。雄性Wistar白化大鼠用甲醇(2.37 g/kg体重,腹腔注射)中毒1天、15天和30天。甲醇给药后,第1天组的下丘脑和肾上腺中酶促抗氧化剂(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶)、非酶促抗氧化剂(还原型谷胱甘肽和维生素C)以及脂质过氧化(LPO)显著增加。然而,在第15天和30天组中观察到酶促和非酶促抗氧化剂减少,同时LPO水平升高。第1天和15天组的血浆皮质酮水平显著升高,而与对照动物相比,30天甲醇中毒组的皮质酮水平显著降低。足垫厚度的细胞介导免疫反应显著降低,白细胞迁移抑制增加。甲醇中毒组的抗体滴度体液免疫反应升高。发现中性粒细胞功能、黏附率和吞噬指数(PI)显著降低。此外,在甲醇暴露动物中观察到亲和力指数和硝基蓝四氮唑还原显著增加。与对照组相比,第1天甲醇暴露组的PI增加。甲醇暴露30天显示下丘脑、肾上腺和脾脏中的DNA片段化增加。总之,暴露于甲醇诱导的氧化应激会扰乱HPA轴功能,改变皮质酮水平,从而导致实验大鼠出现不同的非特异性和特异性免疫反应。