Toxicity of neomycin on enzyme activities of kidney and duodenal mucosa in vivo: organ specificity and species difference between rats and mice.

S Suzuki, S Hatashima, Y Shinzawa, O Niwa, R Tamatani
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Abstract

Inhibitory effects of neomycin administration (10-80 mg/kg body weight/day, s.c. for 7 days) on several enzyme activities of kidney and duodenal mucosa were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase activity was inhibited by neomycin in a dose-dependent manner, while microsomal Mg(2+)-Na(+)-K(+)-ATPase activity and cytosol carbonic anhydrase (CA) activity were inhibited only by larger doses. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were also inhibited only by larger doses. Serum urea nitrogen (UN) concentration and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were increased in a dose-dependent manner. In ddY and C57black mice, however, all enzyme activities in kidney and duodenal mucosa were almost unaffected by any dose of neomycin and showed no changes in serum UN concentration and urinary NAG activity except for ddY mice in which NAG activity was only increased by the largest dose of neomycin. In light microscopic analysis, 80 mg neomycin/kg produced necrosis in the greater part of rat proximal tubuli with no changes in duodenal brush border. On the other hand, no histological changes were produced in the renal cortex or duodenal mucosa of mice by any dosage. In conclusion, there are organ-specific and species differences in the effects of neomycin between rats and mice.

新霉素对体内肾脏和十二指肠粘膜酶活性的毒性:大鼠和小鼠的器官特异性和物种差异。
比较了新霉素(10 ~ 80 mg/kg体重/d,连续给药7 d)对雄性大鼠和小鼠肾脏和十二指肠黏膜几种酶活性的抑制作用。在Wistar大鼠肾脏,小管刷边界Mg(2+)依赖,HCO3(-)刺激的atp酶活性被新霉素以剂量依赖的方式抑制,而微体Mg(2+)- na (+)- k (+)- atp酶活性和细胞质碳酸酐酶(CA)活性只有在大剂量时才被抑制。在大鼠十二指肠粘膜中,Mg(2+)- hco3 (-)- atp酶和CA活性也只有在大剂量时才会受到抑制。血清尿素氮(UN)浓度和尿n -乙酰- β -d -氨基葡萄糖苷酶(NAG)活性呈剂量依赖性升高。然而,在ddY和C57black小鼠中,肾脏和十二指肠粘膜的所有酶活性几乎不受任何剂量的新霉素的影响,血清UN浓度和尿NAG活性没有变化,除了ddY小鼠NAG活性只有最大剂量的新霉素才增加。光镜分析显示,80mg新霉素/kg使大鼠近端小管大部分坏死,十二指肠刷状缘未见改变。另一方面,任何剂量均未对小鼠肾皮质和十二指肠黏膜产生组织学改变。综上所述,新霉素的作用在大鼠和小鼠之间存在器官特异性和物种差异。
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