Milani Elham, Nikfar Shekoufeh, Khorasani Reza, Zamani Mohammad Jafar, Abdollahi Mohammad
Laboratory of Toxicology, Department of Pharmacology and Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Comp Biochem Physiol C Toxicol Pharmacol. 2005 Feb;140(2):251-5. doi: 10.1016/j.cca.2005.02.010. Epub 2005 Mar 17.
Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg/kg). The effects of 15-days treatment by milrinone, sildenafil, and theophylline as cyclic-AMP and -GMP phosphodiesterase inhibitors (PDEIs) on diabetes-induced oxidative stress were studied. The levels of glucose, malonedialdehyde (MDA) the by product of lipid peroxides, and TAC (FRAP test) were estimated in plasma of control and experimental groups of rats. A significant increase in the levels of plasma glucose, and MDA and a concomitant decrease in the levels of TAC were observed in diabetic rats. These alterations were reverted back to near normal level after the treatment with PDEIs. Treatment of diabetic rats by PDEIs reduced MDA levels and increased TAC in the order of milrinone>sildenafil>theophylline. In conclusion, the present investigation show that PDIS possesses antioxidant activities, which may be attributed to their enhancing effect on cellular cyclic nucleotides contributing to the protection against oxidative stress in streptozotocin-induced diabetes. Exact mechanism of protective actions of cAMP- and cGMP-phosphodiesterase remains to be elucidated by further studies. This finding may suggest a place for PDEIs in maintaining health in diabetes.
氧化应激增加被认为与糖尿病组织损伤的发病机制和进展有关。本研究的目的是探讨不同磷酸二酯酶抑制剂对链脲佐菌素诱导的糖尿病大鼠（褐家鼠）血浆脂质过氧化和总抗氧化能力（TAC）的影响。大鼠通过单次注射链脲佐菌素（STZ，45mg/kg）成为糖尿病大鼠。研究了米力农、西地那非和茶碱作为环磷酸腺苷和环磷酸鸟苷磷酸二酯酶抑制剂（PDEIs）对糖尿病诱导的氧化应激的15天治疗效果。在对照组和实验组大鼠的血浆中估计葡萄糖、脂质过氧化物的副产物丙二醛（MDA）和TAC（FRAP试验）的水平。糖尿病大鼠血浆葡萄糖和MDA水平显著升高，同时TAC水平降低。用PDEIs治疗后，这些改变恢复到接近正常水平。用PDEIs治疗糖尿病大鼠可降低MDA水平，并按米力农>西地那非>茶碱的顺序增加TAC。总之，本研究表明PDEIs具有抗氧化活性，这可能归因于它们对细胞环核苷酸的增强作用，有助于保护链脲佐菌素诱导的糖尿病中的氧化应激。环磷酸腺苷和环磷酸鸟苷磷酸二酯酶保护作用的确切机制仍有待进一步研究阐明。这一发现可能表明PDEIs在维持糖尿病患者健康方面有一席之地。
