Contribution of acetone and osmotic-diuresis by streptozotocin-induced diabetes in attenuation of cephaloridine nephrotoxicity.
Previous studies have indicated that cephaloridine nephrotoxicity was reduced in streptozotocin (STZ)-induced diabetic rats. Experiments were performed to investigate if a shorter duration of diabetes would reduce cephaloridine nephrotoxicity. Studies were also conducted to examine the contribution of osmotic diuresis and ketone accumulation to the mechanism for reduced toxicity. Male Fischer 344 (F344) rats were injected with 30 mg/kg STZ or vehicle. Seven days after STZ or vehicle administration, the animals were treated (i.p.) with 1500 mg/kg cephaloridine. Increased kidney weight, blood urea nitrogen (BUN) level and decreased renal cortical slice accumulation of p-aminohippurate (PAH) and tetraethyl-ammonium (TEA) were measured in the normoglycemic group. No differences in renal function were detected between diabetic groups treated with cephaloridine or vehicle (PFC). Pretreatment of euglycemic rats with 0 or 10% dextrose in the drinking water and by oral gavage failed to prevent the renal damage produced by 1500 mg/kg cephaloridine despite glucosuria and urine output comparable to diabetic animals. However, dextrose-diuresis afforded a slight reduction in toxicity as indicated by changes in kidney weight and renal cortical slice accumulation of PAH and TEA. Pretreatment (oral) with 0 or 1.5 ml/kg acetone had no effect on cephaloridine toxicity (1000 mg/kg, i.p.). These findings suggested that attenuation of cephaloridine toxicity may be independent of the duration of diabetes. These results also indicated that glucose-mediated osmotic diuresis and acetone accumulation cannot account for reduced cephaloridine toxicity in diabetic rats.
Valentovic
M
M
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Ball
J G
JG
Anestis
D
D
D000096:Acetone / Q000633:toxicity*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002509:Cephaloridine / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D004231:Diuresis / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D001786:Blood Glucose; D013757:Tetraethylammonium Compounds; D000096:Acetone; D019789:Tetraethylammonium; D005947:Glucose; D002509:Cephaloridine; D010130:p-Aminohippuric Acid