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Cephaloridine nephrotoxicity in streptozotocin induced diabetic Fischer 344 (F344) rats
M A Valentovic1, J G Ball, C Elliott
1Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
Abstract:
The purpose of this study was to determine if cephaloridine nephrotoxicity is attenuated in streptozotocin (STZ)-induced diabetic rats. Fischer 344 (F344) rats (205-250 g) were given a single injection (i.p.) of STZ (27-35 mg/kg) or citrate buffer. The nephrotoxicity of (750 mg/kg) cephaloridine (i.p.) was then compared with normoglycemic and 14-day diabetic rats. Increased blood urea nitrogen (BUN) levels as well as diminished renal cortical slice accumulation of tetraethylammonium (TEA) and lactate-stimulated p-aminohippurate (PAH) were measured (P less than 0.05) in normoglycemic rats 48 h after cephaloridine administration. Cephaloridine failed to alter BUN levels and organic ion accumulation in diabetic rats. Diabetes did not totally protect against cephaloridine toxicity since kidney weights were elevated in normoglycemic and diabetic rats 48 h after administration of 750 mg/kg cephaloridine. A series of experiments also measured BUN levels, kidney weight and renal cortical slice uptake of PAH and TEA 24, 48 and 72 h after (1500 mg/kg) cephaloridine administration. Cephaloridine increased (P less than 0.05) kidney wt and decreased PAH and TEA uptake (P less than 0.05) in the normoglycemic group at 24-72 h. No change in kidney wt, PAH or TEA uptake was observed in the diabetic rats. These data indicate diabetes reduces cephaloridine nephrotoxicity.
Insights
Diabetes significantly reduces cephaloridine nephrotoxicity in rats. Diabetic rats showed no changes in blood urea nitrogen or organic ion accumulation after cephaloridine exposure, indicating a protective effect against kidney damage.
Area of Science:
- Nephrology
- Pharmacology
- Endocrinology
Background:
- Cephaloridine is an antibiotic known to cause nephrotoxicity.
- Diabetes mellitus can alter drug metabolism and excretion.
- The interaction between cephaloridine and diabetes-induced renal changes requires investigation.
Purpose of the Study:
- To investigate the effect of streptozotocin (STZ)-induced diabetes on cephaloridine nephrotoxicity in Fischer 344 rats.
- To compare the nephrotoxic effects of cephaloridine in normoglycemic versus diabetic rats.
Main Methods:
- Rats were induced with diabetes using streptozotocin (STZ) or given a citrate buffer control.
- Cephaloridine was administered at 750 mg/kg and 1500 mg/kg to normoglycemic and diabetic rats.
- Nephrotoxicity was assessed by measuring blood urea nitrogen (BUN) levels, kidney weight, and renal cortical slice uptake of tetraethylammonium (TEA) and p-aminohippurate (PAH).
Main Results:
- In normoglycemic rats, cephaloridine administration led to increased BUN and decreased TEA/PAH uptake, indicating nephrotoxicity.
- Diabetic rats showed no significant changes in BUN levels or organic ion accumulation after cephaloridine exposure.
- While kidney weights increased in both groups at 750 mg/kg, higher doses (1500 mg/kg) did not alter kidney weight or organic ion uptake in diabetic rats, unlike in normoglycemic rats.
Conclusions:
- Diabetes mellitus attenuates cephaloridine-induced nephrotoxicity in rats.
- The protective effect of diabetes against cephaloridine nephrotoxicity is likely due to altered drug handling or renal compensatory mechanisms.
- These findings suggest potential therapeutic implications for managing antibiotic toxicity in diabetic patients.