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Effect of experimental diabetes mellitus on gentamicin-induced acute renal functional changes in the anaesthetized
K Hamilton1, E J Eaton, H O Garland
1School of Biological Sciences, University of Manchester, UK.
Abstract:
1. Rats with streptozotocin (STZ) diabetes are protected from gentamicin (GEN) nephrotoxicity. Because the chronic renal damage from GEN is preceded by acute renal functional changes (notably hypercalciuria), the present study aims to determine whether diabetes may also protect against the acute effects of the drug. If there is a link between the rapid physiological actions of GEN and its subsequent nephrotoxicity, the former may also be affected by the diabetic condition. 2. Standard renal clearance techniques were performed on anaesthetized rats that had been injected with STZ or vehicle 2 weeks previously. All animals were infused with 0.9% NaCl for 5 h and then either GEN (0.28 mg/kg per min) or 0.9% NaCl alone for 2 h. 3. Baseline fractional calcium excretion (FE(Ca)) of diabetic rats was three-fold that of control animals (6.6+/-0.2 vs 2.2+/-0.2%, respectively; P<0.01, MANOVA). Following GEN infusion, a comparable increase in FE(Ca) occurred in control and diabetic rats (5.3+/-0.6 vs 5.3+/-0.8%, respectively; NS). 4. Streptozotocin diabetes, therefore, does not alter the acute hypercalciuric response to GEN. This may suggest that the acute effects of GEN on renal calcium handling do not contribute to the subsequent nephrotoxicity. However, the higher baseline FE(Ca) seen in diabetic rats may afford protection against the renal injury caused by gentamicin.
Insights
Diabetic rats do not show altered acute responses to gentamicin, suggesting this acute effect is not linked to protection. However, higher baseline calcium excretion in diabetic rats may protect against gentamicin nephrotoxicity.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Gentamicin (GEN) causes nephrotoxicity, preceded by acute renal functional changes like hypercalciuria.
- Streptozotocin (STZ)-induced diabetes in rats demonstrates protection against chronic GEN nephrotoxicity.
- The study investigates if diabetes also protects against the acute renal effects of GEN.
Purpose of the Study:
- To determine if STZ-induced diabetes protects against the acute hypercalciuric response to GEN.
- To explore the link between acute physiological actions of GEN and its subsequent nephrotoxicity in diabetic rats.
Main Methods:
- Standard renal clearance techniques were employed in anesthetized rats.
- Animals were injected with STZ or vehicle 2 weeks prior to the experiment.
- Rats were infused with 0.9% NaCl, followed by either GEN or 0.9% NaCl alone.
Main Results:
- Diabetic rats exhibited a three-fold higher baseline fractional calcium excretion (FE(Ca)) compared to controls.
- GEN infusion resulted in a comparable increase in FE(Ca) in both diabetic and control rats.
- STZ diabetes did not alter the acute hypercalciuric response to GEN.
Conclusions:
- The acute hypercalciuric response to GEN is not affected by STZ-induced diabetes.
- Acute effects of GEN on renal calcium handling may not contribute to its subsequent nephrotoxicity.
- Elevated baseline FE(Ca) in diabetic rats might offer protection against gentamicin-induced renal injury.