Varalakshmi Palaninathan, Sandhya Sunil, Malarkodi Kumaravel Palanichamy
Department of Medical Biochemistry, Dr. A.L Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
Mol Cell Biochem. 2003 Jun;248(1-2):35-40. doi: 10.1023/a:1024141128546.
Gentamicin is an aminoglycosidic antibiotic widely used in the treatment of many gram-negative bacterial infections. The present study was designed to investigate the extent of nephrotoxicity and the degree of protection afforded by lipoic acid under E. coli infected conditions and to note its effect on the antimicrobial activity of gentamicin. The study was carried out with adult male albino rats of Wistar strain. Group I animals served as controls. Group II animals were injected intraperitoneally for 2 successive days with 0.2 ml inoculum containing 10(10)) colony forming units of E. coli. Group III animals were injected E. coli as those in group II, in addition gentamicin 100 mg kg(-1) was administered intraperitoneally for 10 successive days. Group IV animals received intraperitoneal injections of E. coli as above plus gentamicin and also received lipoic acid (25 mg kg(-1)) for 10 days by oral gavage. Rats subjected to E. coli administration showed a decline in the thiol content of the cell accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase and glutathione peroxidase with an added effect observed when gentamicin was administered along with it. The extent of nephrotoxicity induced by gentamicin was clearly evident with the decline in the activities of lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase in the rat renal tissues. A significant decrease was also observed in the activities of the transmembrane enzymes upon gentamicin administration. Treatment with lipoic acid decreased lipid peroxidation thereby maintaining the antioxidant status of the cell. The activities of the renal and transmembrane enzymes were also restored on lipoic acid treatment. The study has highlighted the beneficial effects of lipoic acid against experimental aminoglycoside toxicity in rats rendered bacteremic.
庆大霉素是一种氨基糖苷类抗生素,广泛用于治疗多种革兰氏阴性菌感染。本研究旨在调查在大肠杆菌感染条件下硫辛酸对肾毒性的影响程度以及所提供的保护程度,并观察其对庆大霉素抗菌活性的影响。该研究以成年雄性Wistar品系白化大鼠进行。第一组动物作为对照。第二组动物连续2天腹腔注射含10(10)个大肠杆菌菌落形成单位的0.2 ml接种物。第三组动物像第二组一样注射大肠杆菌,此外连续10天腹腔注射100 mg/kg的庆大霉素。第四组动物像上述那样接受腹腔注射大肠杆菌加庆大霉素,并且还通过口服灌胃10天给予硫辛酸(25 mg/kg)。接受大肠杆菌给药的大鼠细胞内硫醇含量下降,同时丙二醛水平升高,过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶活性降低,当与庆大霉素一起给药时观察到叠加效应。庆大霉素诱导的肾毒性程度在大鼠肾组织中乳酸脱氢酶、碱性磷酸酶和N-乙酰-β-D-葡萄糖苷酶活性下降中明显可见。给予庆大霉素后跨膜酶活性也显著降低。用硫辛酸治疗可降低脂质过氧化,从而维持细胞的抗氧化状态。硫辛酸治疗后肾酶和跨膜酶的活性也得以恢复。该研究突出了硫辛酸对实验性败血症大鼠氨基糖苷类毒性的有益作用。