Patil Madhoosudan A, Suryanarayana Palla, Putcha Uday Kumar, Srinivas Myadara, Reddy G Bhanuprakash
Department of Biochemistry, National Institute of Nutrition, Jamai-Osmania, Hyderabad 500007, India.
Department of Pathology, National Institute of Nutrition, Hyderabad 500007, India.
Oxid Med Cell Longev. 2014;2014:463264. doi: 10.1155/2014/463264. Epub 2014 Nov 19.
Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.
2型糖尿病(T2D)通常继发于糖尿病前期(PD)状态,如空腹血糖受损(IFG)和/或糖耐量受损(IGT)。尽管有研究报道IGT或IFG与白内障有关,但PD相关性白内障的实验依据尚不清楚。因此,我们评估了新生大鼠链脲佐菌素(nSTZ)诱导的模型,通过给2日龄大鼠注射链脲佐菌素(STZ)来研究PD相关性白内障的发生机制。虽然大多数(70%)注射nSTZ的幼崽在两个月时出现了IGT(nSTZ-PD),但即使在七个月后也未出现白内障,其余(30%)的nSTZ大鼠在两个月时出现高血糖(nSTZ-D),并在七个月时出现成熟白内障。晶状体生化分析表明,nSTZ-D白内障晶状体中的超氧化物歧化酶(SOD)活性增加、脂质过氧化和蛋白质羰基水平升高,表明氧化应激增加。通过醛糖还原酶活性和山梨醇水平评估,多元醇途径也增加。尽管nSTZ-PD动物未表现出任何晶状体混浊的迹象,但在晶状体中观察到蛋白质不溶性增加以及多元醇途径增强。此外,IGT动物晶状体中的氧化应激增加。这些结果表明,氧化应激以及增加的多元醇途径可能在IGT相关性晶状体异常中起作用。总之,nSTZ-PD大鼠模型有助于研究IGT相关性晶状体异常。