Hassan N, Janjua M Z
Department of Anatomy, Dow Medical College, Karachi.
J Ayub Med Coll Abbottabad. 2001 Jul-Sep;13(3):26-30.
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.
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.
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).
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.
胰岛素依赖型糖尿病的自然病程特征是胰腺中产生胰岛素的β细胞因自身免疫过程而逐渐遭到破坏。某些β细胞毒素（如用于制作胰岛素依赖型糖尿病动物模型的链脲佐菌素）的毒性作用与氧化应激有关，这是由于受损β细胞中DNA修复增强和烟酰胺腺嘌呤二核苷酸（NAD）耗竭所致。使用烟酰胺可预防链脲佐菌素的这种活性。
设计了一项光学显微镜研究，以确定保护胰腺β细胞免受链脲佐菌素毒性所需的烟酰胺最佳剂量。35只成年雄性白化大鼠被分为A、B、C、D和E五个相等的组。研究持续时间为14天。实验组C、D和E的动物在第1天分别接受250mg/Kg、350mg/Kg和500mg/Kg的单次腹腔注射烟酰胺。A组和B组动物分别作为正常对照和糖尿病对照。除A组动物外，所有动物均同时接受32mg/Kg体重的链脲佐菌素单次腹腔注射。在开始治疗前、48小时后和实验期结束时评估空腹血糖并对动物称重。在研究期结束时进行组织学研究。
C组动物的血糖水平和最终体重与糖尿病对照组的值相符。组织学上，胰腺的β细胞总体质量普遍降低（P<0.001），形态改变。D组动物在48小时时显示糖耐量受损，但在研究期结束时血糖正常。β细胞有一些损失，但大量形态正常的这些细胞（P<0.05）得以保留。E组动物的β细胞数量正常，具有正常的形态特征。这些动物的最终体重和空腹血糖与正常对照组（A组）的值相符。
这些数据表明，就预防链脲佐菌素对白化大鼠的β细胞毒性作用而言，烟酰胺的最佳剂量为500mg/Kg体重。
