Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):808-15.
Diabetic nephro-pathy (DN) is a major cause of morbidity and mortality in diabetic patients. To prevent the development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. Proanthocyanidin (PA) and thymoquinone (TQ) have been reported to be effective in treating DN, while little is known about their mechanism of action and their combination.
This study was designed to investigate the possible beneficial effects of (TQ), (PA) and their combination to attenuate DN in rats.
Rats were divided into five groups: group 1 (control), group 2 (diabetic untreated), group 3 (diabetic treated with PA), group 4 (diabetic treated with TQ) and group 5 (diabetic treated with PA+TQ). Diabetes was induced in groups 2-5 by a single dose of 65 mg/kg streptozotocin (STZ) in citrate buffer pH 4.5. Two days after STZ treatment, development of diabetes in the experimental groups was confirmed by measuring blood glucose. Rats in group 3 were given PA (250 mg/kg), rats in group 4 were given TQ (50 mg/kg) and rats in group 5 were given PA+TQ (250+50 mg/kg respectively) once a day orally for 12 weeks starting 2 days after STZ injection.
In this work, novel data correlate the relation between reactive oxygen species; advanced glycation end products; IL-6 and DN were obtained. Treatment of rats in groups 3-5 with PA, TQ and PA+TQ was significantly increased- the reduced body weight, the reduced glutathione concentration and activity of superoxide dismutase. The elevated levels of urea, creatinine, nitric oxide, malondialdehyde and IL-6 in group 2 were significantly reduced as a result of the treatment.
These findings suggest that PA and TQ treatment exerts a therapeutic protective effect in diabetes by decreasing oxidative stress and attenuating DN. Consequently, TQ and PA may be clinically useful for protecting diabetic kidney against oxidative stress.
糖尿病肾病(DN)是糖尿病患者发病率和死亡率的主要原因。为了预防这种疾病的发展并改善晚期肾损伤,需要针对关键分子靶标进行有效的治疗。原花青素(PA)和百里醌(TQ)已被报道可有效治疗 DN,但它们的作用机制及其联合应用知之甚少。
本研究旨在探讨(TQ)、(PA)及其联合应用对大鼠 DN 的可能有益影响。
大鼠分为五组:第 1 组(对照组)、第 2 组(未治疗的糖尿病组)、第 3 组(用 PA 治疗的糖尿病组)、第 4 组(用 TQ 治疗的糖尿病组)和第 5 组(用 PA+TQ 治疗的糖尿病组)。第 2-5 组大鼠一次性腹腔注射柠檬酸缓冲液 pH4.5 中的 65mg/kg 链脲佐菌素(STZ)诱导糖尿病。STZ 处理后 2 天,通过测量血糖确认实验各组糖尿病的发展。第 3 组大鼠给予 PA(250mg/kg),第 4 组大鼠给予 TQ(50mg/kg),第 5 组大鼠给予 PA+TQ(250+50mg/kg),每天一次,在 STZ 注射后 2 天开始连续 12 周口服给药。
在这项工作中,获得了与活性氧;晚期糖基化终产物;白细胞介素 6 和 DN 之间关系的新数据。用 PA、TQ 和 PA+TQ 治疗组 3-5 的大鼠显著增加了体重减轻、还原型谷胱甘肽浓度和超氧化物歧化酶活性。第 2 组中尿素、肌酐、一氧化氮、丙二醛和白细胞介素 6 水平升高,经治疗后显著降低。
这些发现表明,PA 和 TQ 治疗通过降低氧化应激和减轻 DN 对糖尿病发挥治疗保护作用。因此,TQ 和 PA 可能在临床上对保护糖尿病肾脏免受氧化应激具有重要作用。