Garcia Francisca Adilfa O, Pinto Sofia F, Cavalcante Andrezza F, Lucetti Lívia T, Menezes Silvana Ms, Felipe Cícero Francisco B, Alves Ana Paula Nn, Brito Gerly Anne C, Cerqueira Gilberto S, Viana Glauce Sb
Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil.
Faculty of Medicine Estácio of Juazeiro do Norte, Juazeiro do Norte, Brazil.
Springerplus. 2014 Jun 5;3:283. doi: 10.1186/2193-1801-3-283. eCollection 2014.
Pentoxifylline (PTX), a methyl xanthine derivative, is a phosphodiesterase inhibitor with anti-inflammatory and renoprotective effects in diabetic patients, among other properties. We studied PTX actions and mechanisms in reducing blood biochemical parameters, in diabetic rats. For diabetes induction, alloxan was intravenously administered to male Wistar rats. One group was left untreated and the other ones treated with PTX (25, 50 and 100 mg/kg), glibenclamide or metformin, as references. Forty-eight hours later and after 1-week to 3-month treatments, blood was collected for determination of glycemia, triglycerides, cholesterol, transaminases, fructosamine and glycated hemoglobin. Afterwards, the animals were euthanized and pancreas, liver and kidney processed for histological analyses and immunohistochemistry assays for TNF-alpha, iNOS and COX-2. The results showed that PTX decreased glycemia and also triglyceride levels, starting 1 week after treatments, as compared to the same group before treatments. Glycemia values were brought towards normality, after 1-month treatment. PTX hypoglycemic effects were potentiated by glibenclamide but not by metformin. It also decreased fructosamine and glycated hemoglobin. Some histological and immunohistochemical alterations for TNF-alpha, iNOS and COX-2 in the diabetic pancreas were also reversed by PTX. We conclude that PTX acts similarly to glibenclamide, and its hypoglycemic actions are, partly, a consequence of ATP-sensitive K(+) channels inhibition. In addition, by its anti-inflammatory and antioxidant properties, PTX may be a therapeutic alternative for the treatment of diabetes and its complications.
己酮可可碱(PTX)是一种甲基黄嘌呤衍生物,是一种磷酸二酯酶抑制剂,除了其他特性外,对糖尿病患者具有抗炎和肾脏保护作用。我们研究了PTX在降低糖尿病大鼠血液生化参数方面的作用和机制。为了诱导糖尿病,将四氧嘧啶静脉注射给雄性Wistar大鼠。一组不进行治疗,其他组分别用PTX(25、50和100mg/kg)、格列本脲或二甲双胍作为对照进行治疗。48小时后以及在1周至3个月的治疗后,采集血液以测定血糖、甘油三酯、胆固醇、转氨酶、果糖胺和糖化血红蛋白。之后,对动物实施安乐死,并对胰腺、肝脏和肾脏进行处理,以进行组织学分析以及针对肿瘤坏死因子-α(TNF-α)、诱导型一氧化氮合酶(iNOS)和环氧化酶-2(COX-2)的免疫组织化学检测。结果表明,与治疗前的同一组相比,PTX从治疗1周后开始降低血糖和甘油三酯水平。经过1个月的治疗后,血糖值趋于正常。PTX的降血糖作用被格列本脲增强,但未被二甲双胍增强。它还降低了果糖胺和糖化血红蛋白。PTX还逆转了糖尿病胰腺中TNF-α、iNOS和COX-2的一些组织学和免疫组织化学改变。我们得出结论,PTX的作用与格列本脲相似,其降血糖作用部分是ATP敏感性钾通道抑制的结果。此外,由于其抗炎和抗氧化特性,PTX可能是治疗糖尿病及其并发症的一种治疗选择。