Stefanović V, Vlahović P, Savić V, Ilić S, Mitić-Zlatković M
Institute of Nephrology and Hemodialysis, University School of Medicine, Nis, Yugoslavia.
Cell Physiol Biochem. 1998;8(5):278-84. doi: 10.1159/000016289.
The clinical use of gentamicin is associated by nephrotoxicity in over 10% of patients. However, the biochemical events responsible for proximal tubular injury and acute renal failure (ARF) are still unclear. In the present study, effects of gentamicin and, comparatively, of mercuric chloride upon rat kidney cortex ectopeptidases were studied. Gentamicin was given i.p., 100 mg/kg daily for up to 6 days, mercuric chloride i.p. once 2.5 mg/kg to rats studied after 3 days. Kidney cortex aminopeptidase N decreased significantly after 3 and 6 days' treatment (p < 0.01), however, angiotensinase A significantly decreased after 3 (p < 0.01), and much more after 6 days of gentamicin treatment (p < 0.001). Dipeptidylpeptidase IV activity was significantly decreased only after 6 days of treatment with gentamicin. In mercuric chloride-induced ARF all three peptidase activities were markedly decreased (p < 0.001). These results suggest that gentamicin-induced decrease in ectopeptidase activities could compromise vasoactive and other biologically active peptides handling, with important consequences upon renal function and metabolism.
庆大霉素的临床应用在超过10%的患者中与肾毒性相关。然而，导致近端肾小管损伤和急性肾衰竭（ARF）的生化事件仍不清楚。在本研究中，研究了庆大霉素以及相对地，氯化汞对大鼠肾皮质外肽酶的影响。给大鼠腹腔注射庆大霉素，剂量为每日100 mg/kg，持续6天；给大鼠腹腔注射一次氯化汞，剂量为2.5 mg/kg，3天后进行研究。治疗3天和6天后，肾皮质氨肽酶N显著降低（p < 0.01），然而，血管紧张素酶A在庆大霉素治疗3天后显著降低（p < 0.01），在治疗6天后降低得更多（p < 0.001）。仅在庆大霉素治疗6天后，二肽基肽酶IV活性显著降低。在氯化汞诱导的急性肾衰竭中，所有三种肽酶活性均显著降低（p < 0.001）。这些结果表明，庆大霉素诱导的外肽酶活性降低可能会损害血管活性肽和其他生物活性肽的处理，对肾功能和代谢产生重要影响。
