Comparison of gentamicin nephrotoxicity between rats and mice.
Toxic effects of gentamicin administration (10-80 mg/kg body weight, subcutaneously (s.c.), once daily for 7 days) on several enzyme activities of kidney and duodenal mucosa together with other parameters were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activity was inhibited by 40-80 mg/kg gentamicin in an almost dose-dependent manner with no changes in microsomal Mg(2+)-Na(+)-K(+)-ATPase activity. Cytosol carbonic anhydrase (CA) activity was inhibited only by 80 mg/kg gentamicin. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were unchanged by any dose of gentamicin. Rat serum urea nitrogen (UN), GOT and GPT concentrations and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were significantly increased by 80 mg/kg gentamicin. In ddY mice, however, almost all parameters described above were unaffected by gentamicin except for the urinary NAG activity which was increased only by 80 mg/kg gentamicin. The concentration of gentamicin in cytosol of rat whole kidney was approximately 3.4-fold higher compared with that in mouse kidney after 80 mg/kg treatment. In light microscopic analysis, 80 mg/kg gentamicin produced necrosis in the greater part of rat kidney proximal tubuli with no pathological findings in mouse kidney. In conclusion, Mg(2+)-HCO3(-)-ATPase activity in brush border membrane of rat proximal tubuli was selectively damaged in gentamicin nephrotoxicity, indicating that the rats are the suitable model for studies of gentamicin nephrotoxicity in humans.
Suzuki
S
S
Department of Pharmacology, Kanazawa Medical University, Ishikawa, Japan.
Takamura
S
S
Yoshida
J
J
Shinzawa
Y
Y
Niwa
O
O
Tamatani
R
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005839:Gentamicins / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D005839:Gentamicins; D017301:Ca(2+) Mg(2+)-ATPase; C030704:magnesium sodium potassium ATPase; C032666:magnesium-bicarbonate ATPase; D002256:Carbonic Anhydrases; D000254:Sodium-Potassium-Exchanging ATPase