Early onset of cisplatin-induced nephrotoxicity in streptozotocin-diabetic rats treated with insulin.
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 (microg/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.
Sarangarajan
Rangaprasad
R
Massachusetts College of Pharmacy and Health Sciences, School of Pharmacy-Worcester, 19 Foster Street, Worcester, Massachusetts 01608, USA. rsarangarajan@mcp.edu
Cacini
William
W
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D006442:Glycated Hemoglobin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D008297:Male; D010984:Platinum / Q000737:chemistry / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D002945:Cisplatin; D006442:Glycated Hemoglobin; D007336:Insulin, Isophane; D010984:Platinum; D013311:Streptozocin