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衰老肾脏对奎尼丁的易感性。

Susceptibility of ageing kidney to quinidine.

作者信息

Agarwal A K, Rao S S

机构信息

Department of Sciences, John Jay College of CUNY, NY 10019.

出版信息

Pharmacol Res. 1994 Feb-Mar;29(2):145-54. doi: 10.1016/1043-6618(94)80038-3.

Abstract

Male Fischer-344 rats aged 3-4 months and 30-32 months were used in this study. Quinidine in vitro reduced accumulation of organic ions, p-ammonium hippurate (PAH) and tetraethyl ammonium (TEA), inhibited oxygen consumption and increased LDH leakage, in renal cortical slices. High concentrations of quinidine (2 and 3 mmol l-1) produced overt toxicity and no age related differences in any of the parameters measured were observed. But at lower concentrations significant age-related differences in kidney susceptibility to quinidine were evident. Administration of 75 mg kg-1 day-1 quinidine for 4 days caused exacerbated renal damage in senescent rats compared to young adults as demonstrated by greater elevation of blood urea nitrogen and serum creatinine, and greater inhibition of TEA uptake in renal cortical slices. These results establish significant age related differences in renal damage due to quinidine.

摘要

本研究使用了3至4个月龄和30至32个月龄的雄性Fischer-344大鼠。在肾皮质切片中,奎尼丁在体外可减少有机离子、对氨基马尿酸(PAH)和四乙铵(TEA)的蓄积,抑制氧消耗并增加乳酸脱氢酶(LDH)泄漏。高浓度的奎尼丁(2和3 mmol l-1)产生明显毒性,在所测量的任何参数中均未观察到与年龄相关的差异。但在较低浓度下,肾脏对奎尼丁的易感性存在明显的年龄相关差异。与年轻成年大鼠相比,以75 mg kg-1天-1的剂量给予奎尼丁4天会导致衰老大鼠的肾损伤加剧,这表现为血尿素氮和血清肌酐的升高幅度更大,以及肾皮质切片中TEA摄取的抑制作用更强。这些结果证实了奎尼丁所致肾损伤存在显著的年龄相关差异。

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