Comparative studies of in vitro renal cephaloridine toxicity between normoglycemic and diabetic rats.
This study investigated if the attenuation in cephaloridine toxicity associated with streptozotocin (STZ)-induced diabetes can be attributed to a direct cellular effect. Comparative studies examined the direct toxicity of cephaloridine 14 days after (35 mg kg-1, i.p.) STZ or vehicle injection of male Fischer 344 (F344) rats. In vitro cephaloridine toxicity was assessed by measuring lipid peroxidation, renal gluconeogenesis and organic ion accumulation in renal cortical slices. The in vitro toxicity of cephaloridine was reduced in the diabetic group since lipid peroxidation was not increased following a 120-min exposure to cephaloridine. This was in contrast to a concentration- and time-dependent increase in lipid peroxidation in renal tissue derived from normoglycemic animals pre-incubated with 0-5 mM cephaloridine. Renal gluconeogenesis was inhibited in a concentration-dependent manner in the normoglycemic group following a 15-90-min exposure to 0-5 mM cephaloridine. Pyruvate-stimulated gluconeogenesis was diminished in the diabetic group only after a 90-min preincubation. Renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) was decreased in the normoglycemic group. Accumulation of TEA, but not PAH, was decreased (P less than 0.05) in the diabetic group. These results indicate that in vitro cephaloridine toxicity was attenuated by STZ-induced diabetes.
Valentovic
M A
MA
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Jeffrey
W
W
Ball
J G
JG
Bailly
D
D
Morenas
M
M
Kinder
J
J
D000818:Animals; D002509:Cephaloridine / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005943:Gluconeogenesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013268:Stimulation, Chemical; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000493:pharmacokinetics; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D007773:Lactates; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D002509:Cephaloridine; D010130:p-Aminohippuric Acid