Normalization of Hyperglycaemia by Oral Vanadyl Sulfate Does Not Reverse Diabetes-Induced Protection against Cisplatin Nephrotoxicity in Streptozotocin-Diabetic Rats.

Autor: Sarangarajan, Rangaprasad, Cacini, William
Zdroj: Pharmacology & Toxicology; 1999, Vol. 85 Issue 6, p169-173, 5p
Abstrakt: Streptozotocin- and galactose-induced diabetic rats are protected against nephrotoxic effects of cisplatin. While the mechanism remains to be defined, protection is associated with a decrease in the accumulation of platinum in renal cortical tissues of streptozotocin-diabetic versus non-diabetic rats. A physiological abnormality common to streptozotocin and galactosemic models of diabetes is hyperglycaemia, suggesting that elevated sugars are involved in mediating protection of diabetic kidney against cisplatin nephrotoxicity. The current study focused on the effect of normalization of hyperglycaemia by vanadyl sulfate trihydrate on the initiation of protection and accumulation of platinum in kidneys of streptozotocin-diabetic rats. Streptozotocin-diabetic rats were treated with 0.75 mg/ml of vanadyl sulfate trihydrate in drinking water to normalize streptozotocin-induced hyperglycaemia. Vanadyl sulfate treatment normalized plasma glucose and glycosylated haemoglobin levels in streptozotocin-diabetic rats to values observed for non-diabetic rats. Intraperitoneal administration of cisplatin (5 mg/kg body weight) increased blood urea nitrogen by a factor >2.5 over baseline in both untreated and vanadyl-treated non-diabetic groups. Cisplatin-induced increases in blood urea nitrogen were 1.6 times baseline in both untreated and vanadyl-treated streptozotocin-diabetic rats. Renal platinum accumulation was significantly lower in streptozotocin-diabetic versus non-diabetic rats regardless of vanadyl sulfate treatment. Renal vanadium levels in all groups of diabetic rats were not significantly different from each other. These results indicate that normalization of plasma glucose levels with vanadyl sulfate in streptozotocin-diabetic rats did not reverse protection of streptozotocin-diabetic kidney against cisplatin nephrotoxicitv. [ABSTRACT FROM AUTHOR]
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