The optimum dose of nicotinamide for protection of pancreatic beta-cells against the cytotoxic effect of streptozotocin in albino rat.
BACKGROUND
The natural course of Insulin Dependent Diabetes Mellitus is characterized by progressive destruction of insulin producing beta-cells of the pancreas resulting from an autoimmune process. The toxic effect of some beta-cells toxins like streptozotocin (used to produce animal models of IDDM) has been associated with the oxidative stress due to enhanced DNA repair and NAD depletion in damaged beta-cells. This activity of streptozotocin has been prevented with the use of nicotinamide.


METHODS
A light microscopic study was designed to determine the optimum dose of nicotinamide required for protection of pancreatic beta-cells against the toxicity of streptozotocin. 35 adult male albino rats were divided into five equal groups A, B, C, D and E. the duration of study was 14 days. The animals in experimental groups C, D and E received a single intraperitoneal injection of nicotinamide 250 mg/Kg, 350 mg/Kg and 500 mg/Kg respectively on day one. Animals in group A and B acted as normal control and diabetic control respectively. All the animals except those in group A received simultaneous injection of streptozotocin 32 mg/Kg body weight intraperitoneally in a single dose. Fasting blood glucose was assessed and the animals weighed before starting the treatment, after 48 hours and at the end of the experimental period. Histological studies were carried out at the end of the study period.


RESULTS
The blood glucose level and the final body weight of the animals in group C matched the values in diabetic control. Histologically the pancreas had generally reduced beta-cells mass (P < 0.001) with altered morphology. The animals in group D showed impaired glucose tolerance at 48 hours but were normoglycaemic at the end of the study period. There was some loss of beta-cells but a significant number of these cells (P < 0.05) showing normal morphology were saved. The animals in group E had normal number of beta-cells having normal morphological features. The final body weight and fasting blood glucose of these animals matched the values in normal control (group A).


CONCLUSIONS
These data suggest that the optimum dose of nicotinamide in regard to prevention against the beta-cytotoxic effect of streptozotocin in albino rat is 500 mg/Kg body weight.
Hassan
N
N
Department of Anatomy, Dow Medical College, Karachi.
Janjua
M Z
MZ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009536:Niacinamide / Q000008:administration & dosage* / Q000627:therapeutic use; D018384:Oxidative Stress; D051381:Rats; D013311:Streptozocin / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D009536:Niacinamide; D013311:Streptozocin