Protective Role of Melatonin and Insulin in Streptozotocin induced Nephrotoxicity in Albino Rats

Aims: To evaluate the protective role of melatonin and insulin on the morphology of proximal convoluted tubules(PCT) of albino rats made nephrotoxic by a chemotherapeutic drug like streptozotocin (STZ). Study design: Prospective experimental study. Place and duration of study: Department of Anatomy, Basic Medical Sciences Institute (BMSI), Jinnah Post Graduate Medical Center (JMPC), Karachi, for 6 weeks from March to April, 2012. Material and methods: 60 male albino rats were divided into 4 groups, containing 15 animals each. Group(gp) A was treated as control, gp B, C and D received 37 mg/kg STZ Intraperitoneally (I/P) once at the start of experiment, whereas gp C additionally received 10mg/100 ml of melatonin (MEL) 3-days prior to STZ administration, and gp D received MEL at the same dose along with subcutaneous INS at a dose of 1 unit per 100 grams body weight. Serum glucose was measured weekly. Body weights were recorded at the start and end of experiment, and the relative kidney weights were recorded after sacrificing the animals. The kidneys were processed for histological examination and periodic Acid Schiff Haematoxylin (PAS-H) stained sections were viewed under the light microscope for detailed morphological examination of the proximal convoluted tubules in all groups of rats. Results: The microscopic examination revealed marked epithelial, cytoplasmic and nuclear changes in the P.C.T. of STZ treated gp B, a significant reduction in the severity of these changes in MEL treated gp C and complete restoration of morphology in MEL and INS treated group D. Serum glucose was significantly increased in both gp B and C and significantly restored in group D. STZ significantly decreased body weight of animals and increased relative weights of kidneys in gp B. MEL treatment in gp C significantly resorted the relative kidney weights but the body weights could not be restored in gp C, whereas in gp D, the animals gained a normal amount of body weight during 6 weeks as they did in control gp A and the relative kidney weights were also similar to those of control gp. Conclusions: The results of the investigation indicated that concomitant administration of MEL and INS suppressed the progression of renal injury induced by nephrotoxic drugs like STZ. MEL alone significantly suppressed the histopathological damage to the P.C.T. but It could not decrease STZ induced hyperglycemia. Therefore, to counteract the nephrotoxicity and hyperglycemia induced by STZ, both MEL and INS should be administered concomitantly.