Toxicity of neomycin on enzyme activities of kidney and duodenal mucosa in vivo: organ specificity and species difference between rats and mice.
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.
Suzuki
S
S
Department of Pharmacology, Kanazawa Medical University, Ishikawa, Japan.
Hatashima
S
S
Shinzawa
Y
Y
Niwa
O
O
Tamatani
R
R
D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors / Q000652:urine; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007672:Kidney Cortex / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008871:Microvilli / Q000187:drug effects / Q000648:ultrastructure; D009355:Neomycin / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D002257:Carbonic Anhydrase Inhibitors; D000118:Acetylglucosaminidase; D000251:Adenosine Triphosphatases; D009355:Neomycin