Kacew S
Department of Pharmacology, University of Ottawa, Ontario, Canada.
J Pharmacol Exp Ther. 1989 Jan;248(1):360-6.
Daily s.c. injection of gentamicin at either 100 mg/kg for 4 days or 60 mg/kg for 2 weeks produced nephrotoxicity in the adult rat as judged by an increase in urinary excretion of beta-galactosidase, beta-glucuronidase and beta-N-acetylglucosaminidase. The observed enzymuria was associated with significant elevation in total renal phospholipid, phosphatidylinositol, phosphatidylcholine and phosphatidylserine. In addition, gentamicin decreased the activities of renal cortical Na+-K+-adenosine triphosphatase, alkaline phosphatase as well as phospholipase C. Pyridoxal-5'-phosphate (250 mg/kg/day) administered i.p. for 4 or 14 days did not markedly alter the metabolic markers of kidney function. In rats simultaneously given pyridoxal-5'-phosphate and gentamicin for 4 days the vitamin failed to prevent either the antibiotic-induced decrease in renal phospholipase C and alkaline phosphatase or the increase in total renal phospholipid, phosphatidylinositol, phosphatidylcholine and phosphatidylserine. However, simultaneous pyridoxal-5'-phosphate and aminoglycoside treatment for 2 weeks proved effective in blockade of the gentamicin-induced kidney phospholipidosis, elevation in urinary beta-galactosidase, beta-glucuronidase and beta-N-acetylglucosaminidase, as well as reduction in renal phospholipase C and alkaline phosphatase. The gentamicin-induced nephrotoxicity was associated with a decrease in renal pyridoxal-5'-phosphate levels. In the simultaneous 4-day-treated rat the renal concentration of pyridoxal-5'-phosphate returned to approximate control values, whereas after 2 weeks the level of vitamin B6 was approximately 2-fold higher than control. Although pyridoxal-5'-phosphate in the simultaneous group lowered kidney gentamicin content by 40% after 4 or 14 days, protection from aminoglycoside-induced nephrotoxicity was apparent only after 2 weeks in our study.(ABSTRACT TRUNCATED AT 250 WORDS)
成年大鼠每日皮下注射庆大霉素，剂量为100mg/kg，共4天，或60mg/kg，共2周，结果显示出现了肾毒性，这可通过β-半乳糖苷酶、β-葡萄糖醛酸酶和β-N-乙酰氨基葡萄糖苷酶尿排泄增加来判断。观察到的酶尿与总肾磷脂、磷脂酰肌醇、磷脂酰胆碱和磷脂酰丝氨酸显著升高有关。此外，庆大霉素降低了肾皮质钠钾-腺苷三磷酸酶、碱性磷酸酶以及磷脂酶C的活性。腹腔注射磷酸吡哆醛（250mg/kg/天），持续4天或14天，并未显著改变肾功能的代谢指标。在同时给予磷酸吡哆醛和庆大霉素4天的大鼠中，该维生素未能预防抗生素诱导的肾磷脂酶C和碱性磷酸酶降低，也未能预防总肾磷脂、磷脂酰肌醇、磷脂酰胆碱和磷脂酰丝氨酸增加。然而，同时给予磷酸吡哆醛和氨基糖苷类药物治疗2周，证明可有效阻断庆大霉素诱导的肾磷脂沉积、尿β-半乳糖苷酶、β-葡萄糖醛酸酶和β-N-乙酰氨基葡萄糖苷酶升高，以及肾磷脂酶C和碱性磷酸酶降低。庆大霉素诱导的肾毒性与肾磷酸吡哆醛水平降低有关。在同时治疗4天的大鼠中，肾磷酸吡哆醛浓度恢复到近似对照值，而2周后维生素B6水平比对照高约2倍。尽管同时给药组的磷酸吡哆醛在4天或14天后使肾庆大霉素含量降低了40%，但在我们的研究中，仅在2周后才明显观察到对氨基糖苷类诱导的肾毒性的保护作用。（摘要截选至250词）
