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Early Onset of Cisplatin‐Induced Nephrotoxicity in Streptozotocin‐Diabetic Rats Treated with Insulin *
Author(s) -
Sarangarajan Rangaprasad,
Cacini William
Publication year - 2004
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2004.950204.x
Subject(s) - streptozotocin , nephrotoxicity , medicine , endocrinology , blood urea nitrogen , diabetes mellitus , insulin , cisplatin , kidney , intraperitoneal injection , creatinine , chemotherapy
Mechanism of protection against cisplatin nephrotoxicity in streptozotocin‐diabetic rats is unclear but is associated with decreased renal platinum accumulation. This study was designed to determine whether normalization of hyperglycaemia by insulin treatment to six week streptozotocin‐diabetic rats reversed protection against cisplatin nephrotoxicity. Male Sprague‐Dawley rats divided into 3 groups (n=10/group) (1) non‐diabetic (2) untreated streptozotocin‐diabetic and (3) insulin‐treated streptozotocin‐diabetic groups were rendered diabetic using streptozotocin (65 mg/kg body weight, intravenous). At the end of 6 weeks, Group 3 animals were treated with insulin (subcutaneously) for 21 days to normalize glucose. After 21 days of insulin treatment, the mean±S.D. plasma glucose (mg%) in Group 3 animals at 144.8±22.03, was significantly lower than Group 2 animals (412±24.69) and comparable to age‐matched non‐diabetic (Group 1) animals. Blood urea nitrogen at 24 hr after intraperitoneal administration of cisplatin (5 mg/kg body weight) increased by a factor 2.5 in Group 3 compared to 1.1 and 1.3 in Group 1 and Group 2 animals respectively. In the same animals, at 96 hr the blood area nitrogen increased by a factor of 3.2 and 2.9 in Group 1 and Group 3 respectively compared to 1.14 for Group 2 animals. Renal platinum levels in Group 1, Group 2 and Group 3 after 96 hr after cisplatin administration were 6.92±0.83, 3.46±0.77 & 6.20±0.64 (μg/g wet weight of tissue) respectively. Results indicate that 21 day insulin treatment to streptozotocin‐diabetic animal reverses protection against cisplatin toxicity. Moreover, insulin treatment increased the susceptibility of streptozotocin‐diabetic rats to cisplatin‐induced renal toxicity.