Kuhad Anurag, Sachdeva Anand Kamal, Chopra Kanwaljit
Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160 014, India.
J Agric Food Chem. 2009 Jul 22;57(14):6123-8. doi: 10.1021/jf901388g.
Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the United States and Europe. Approximately 30-40% of patients with type I and 15% with type II diabetes mellitus develop end ESRD. The study was designed to evaluate the impact of sesamol on renal function and renoinflammatory cascade in streptozotocin (STZ)-induced diabetes. STZ-induced diabetic rats were treated with sesamol (2, 4, and 8 mg/kg/day; po) or with vehicle from the fifth to eighth weeks. After 8 weeks, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine, and urea clearance were measured. Cytoplasmic and nuclear fractions of kidney were prepared for the quantification of oxidative-nitrosative stress (lipid peroxidation, superoxide dismutase, catalase, nonprotein thiols, total nitric oxide), tumor necrosis factor-alpha (TNF-alpha), tissue growth factor-1 beta (TGF-beta1), p65 subunit of NFkappabeta, and caspase-3. After 8 weeks of STZ injection, the rats produced significant alteration in renal function, increased oxidative-nitrosative stress, TNF-alpha, TGF-beta1, caspase-3 activity in cytoplasmic lysate, and active p65 subunit of NFkappabeta in nuclear lysate of kidney of diabetic rats. Interestingly, co-administration of sesamol significantly and dose-dependently prevented biochemical and molecular changes associated with diabetes. Moreover, diabetic rats treated with insulin-sesamol combination produced more pronounced effect on molecular parameters as compared to their respective groups. The data reveal that sesamol modulates the release of profibrotic cytokines, oxidative stress, ongoing chronic inflammation, and apoptosis and thus exerts a marked renoprotective effect.
糖尿病已成为美国和欧洲终末期肾病（ESRD）最常见的单一病因。约30%-40%的I型糖尿病患者和15%的II型糖尿病患者会发展为终末期肾病。本研究旨在评估芝麻酚对链脲佐菌素（STZ）诱导的糖尿病大鼠肾功能及肾炎症级联反应的影响。从第5周开始至第8周，对STZ诱导的糖尿病大鼠给予芝麻酚（2、4和8mg/kg/天；口服）或赋形剂。8周后，测量尿白蛋白排泄量、尿量、血清肌酐、血尿素氮、肌酐及尿素清除率。制备肾脏的细胞质和细胞核组分，以定量氧化亚硝化应激（脂质过氧化、超氧化物歧化酶、过氧化氢酶、非蛋白硫醇、总一氧化氮）、肿瘤坏死因子-α（TNF-α）、组织生长因子-1β（TGF-β1）、NFκB的p65亚基和半胱天冬酶-3。注射STZ 8周后，大鼠肾功能出现显著改变，糖尿病大鼠肾脏细胞质裂解物中的氧化亚硝化应激、TNF-α、TGF-β1、半胱天冬酶-3活性以及细胞核裂解物中NFκB的活性p65亚基均增加。有趣的是，联合给予芝麻酚可显著且剂量依赖性地预防与糖尿病相关的生化和分子变化。此外，与各自单独给药组相比，胰岛素-芝麻酚联合治疗的糖尿病大鼠对分子参数产生了更显著的影响。数据表明，芝麻酚可调节促纤维化细胞因子的释放、氧化应激、持续的慢性炎症和细胞凋亡，从而发挥显著的肾脏保护作用。
