CEPHALORIDINE IN-VITRO TOXICITY AND ACCUMULATION IN RENAL SLICES FROMNORMOGLYCEMIC AND DIABETIC RATS

Previous work has shown a reduction in cephaloridine nephrotoxicity in a diabetic rat model. The following studies examined in vitro cephalo ridine toxicity in renal slices from normoglycemic and diabetic Fische r 344 rats. Diabetes was induced by acute intraperitoneal injection of 35 mg/kg streptozotocin. Renal cortical slices were isolated from nor moglycemic and diabetic animals. Tissues were exposed to 0-5 mM cephal oridine for 15-120 min. Pyruvate-directed gluconeogenesis was diminish ed in ail groups exposed to 2-5 mM cephaloridine for 60-120 min. Leaka ge of lactate dehydrogenase (LDH) was apparent only in the normoglycem ic group in the presence of 4-5 mM cephaloridine for 120 min. LDH leak age was not increased at any cephaloridine concentration in the diabet ic tissue. Total glutathione levels were compared in renal cortical sl ices exposed to cephaloridine for 30-120 min. Baseline values for glut athione were comparable between normoglycemic and diabetic tissue sugg esting that the mechanism for reduced toxicity was not due to higher g lutathione levels in diabetic tissue. Total glutathione levels were di minished more rapidly in normoglycemic than diabetic tissue by incubat ion with 5 mM cephaloridine. Comparison of cephaloridine accumulation indicated that diabetic tissue accumulated less cephaloridine than the normoglycemic group when tissues were incubated with 0-2 mM cephalori dine. However, renal slice accumulation was similar between normoglyce mic and diabetic groups following in vitro incubation with 4-5 mM ceph aloridine. These results suggest that the mechanism for reduced in vit ro cephaloridine toxicity in diabetic tissue cannot be limited to diff erences in accumulation and must include an unidentified cellular comp onent. (C) 1997 Society of Toxicology.