Selvakumar Elangovan, Prahalathan Chidambaram, Mythili Yenjerla, Varalakshmi Palaninathan
Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Chem Biol Interact. 2005 Feb 28;152(1):59-66. doi: 10.1016/j.cbi.2005.01.009.
The present study investigated the protective efficacy of dl-alpha-lipoic acid on the peroxidative damage and abnormal antioxidant levels in the mitochondrial fraction of testis in cyclophosphamide (CP) administered rats. Male Wistar rats of 140+/-20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce testicular toxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks, 24 h prior to CP administration). A vehicle-treated control group and a lipoic acid drug control group were also included. The mitochondrial fraction of untreated CP-exposed testis showed 1.84-fold increase in lipid peroxidation, along with a significant (P<0.001) increase in hydrogen peroxide levels. In CP-exposed rats, we observed abnormal changes in the activities/levels of mitochondrial enzymic (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non-enzymic (reduced glutathione, ascorbate and alpha-tocopherol) antioxidants. CP-treated rats also showed decline in the activities of mitochondrial enzymes such as succinate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase. In contrast, rats pretreated with lipoic acid showed normal lipid peroxidation and antioxidant defenses, thereby showing the protection rendered by lipoic acid.
本研究调查了dl-α-硫辛酸对环磷酰胺(CP)处理大鼠睾丸线粒体部分过氧化损伤及抗氧化水平异常的保护作用。将体重140±20 g的雄性Wistar大鼠分为四组。两组给予CP(每周一次口服灌胃15 mg/kg体重,共10周)以诱导睾丸毒性;其中一组接受硫辛酸治疗(每周一次腹腔注射35 mg/kg体重,共10周,在给予CP前24小时)。还包括一个溶剂对照组和一个硫辛酸药物对照组。未处理的CP暴露睾丸的线粒体部分脂质过氧化增加了1.84倍,同时过氧化氢水平显著升高(P<0.001)。在CP暴露的大鼠中,我们观察到线粒体酶(超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶)和非酶(还原型谷胱甘肽、抗坏血酸和α-生育酚)抗氧化剂的活性/水平发生异常变化。CP处理的大鼠还表现出线粒体酶如琥珀酸脱氢酶、苹果酸脱氢酶和异柠檬酸脱氢酶的活性下降。相反,用硫辛酸预处理的大鼠脂质过氧化和抗氧化防御正常,从而显示出硫辛酸的保护作用。