Toutain H, Olier B, Fillastre J P, Morin J P
Pathol Biol (Paris). 1986 Jun;34(5 Pt 2):582-6.
Some loop diuretics seem to increase gentamicin nephrotoxicity. We investigated this property for a new diuretic, muzolimine, in female Wistar rats. Each rat was given gentamicin intraperitoneally in a dosage that induces morphological and functional modifications in the kidneys (20 mg/kg/day for 7 days). Muzolimine was given in a daily dosage of 15 mg/kg starting 15 days before the first gentamicin injection and continuing throughout the seven-day gentamicin course. As compared to controls given gentamicin alone, modifications induced by the muzolimine-gentamicin combination showed no significant differences for the following criteria: renal accumulation of gentamicin, membrane lysosomal latency, renal oxidative mitochondrial metabolism and cortical activity of renal cathepsin B, N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase. However, slightly lower sphingomyelinase activities (p less than 0.05) were found for muzolimine + gentamicin as compared to gentamicin alone. Urinary NAG excretion increase more with muzolimine + gentamicin than with gentamicin alone, perhaps as a result of the very significant increase in urinary output observed with the diuretic. Our results show that, in contrast to findings with another loop diuretic, furosemide, the renal toxicity of gentamicin is not noticeably modified by concomitant administration of muzolimine.
一些袢利尿剂似乎会增加庆大霉素的肾毒性。我们在雌性Wistar大鼠中研究了一种新型利尿剂莫唑胺的这一特性。每只大鼠腹腔注射庆大霉素，剂量为能引起肾脏形态和功能改变的剂量（20mg/kg/天，共7天）。莫唑胺从首次注射庆大霉素前15天开始，以每日15mg/kg的剂量给药，并在整个7天的庆大霉素疗程中持续给药。与单独给予庆大霉素的对照组相比，莫唑胺 - 庆大霉素联合用药引起的改变在以下指标上无显著差异：庆大霉素在肾脏中的蓄积、膜溶酶体潜伏性、肾脏线粒体氧化代谢以及肾脏组织蛋白酶B、N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）和丙氨酸氨基肽酶的皮质活性。然而，与单独使用庆大霉素相比，莫唑胺 + 庆大霉素组的鞘磷脂酶活性略低（p小于0.05）。与单独使用庆大霉素相比，莫唑胺 + 庆大霉素组的尿NAG排泄增加更多，这可能是由于利尿剂导致尿量显著增加的结果。我们的结果表明，与另一种袢利尿剂呋塞米的研究结果相反，同时给予莫唑胺不会明显改变庆大霉素的肾毒性。
