Gazi University, Faculty of Medicine, Department of Medical Biochemistry, Tandogan, Ankara, Turkey.
Eur J Pharmacol. 2011 Mar 1;654(1):80-5. doi: 10.1016/j.ejphar.2010.11.035. Epub 2010 Dec 21.
One of the main goals of treatment of diabetes mellitus is to prevent its complications. Oxidative stress is universal in diabetes, being ultimately involved with the development complications. As a result of hyperglycemia, reactive oxygen/nitrogen species are produced in various tissues that leads to tissue damage with lipid peroxidation and protein oxidation, along with disruption in cellular homeostasis and accumulation of damaged molecules. Hence, supplementation with antioxidant compounds may offer some protection against diabetic complications. The pleiotropic effects of statins, including antioxidant and anti-inflammatory properties, represent an area of great interest in prevention and therapy of cardiovascular and neurological disorders. Using biomarkers of oxidative stress, in this study we examined the effect of non cholesterol lowering dose, long term fluvastatin treatment on oxidative stress in streptozotocin-diabetic rats. Experiments were conducted in 24 Wistar adult male rats. Diabetic and non-diabetic rats were treated orally for 6 months with fluvastatin (2mg/kg/day, p.o) starting one week after streptozotocin injection (55 mg/kg, i.p.), (preventive study). In brain, heart, liver, pancreas and kidney homogenates malondialdehyde, lipid hydroperoxide, protein carbonyl content, advanced oxidation protein products, 3-nitrotyrosine levels and superoxide dismutase, catalase activities were measured. Hyperglycemia and dyslipidemia in diabetic groups remained unchanged after fluvastatin treatment. The drug act as antioxidant in the tissues. Hence, antioxidant property of fluvastatin, independent of cholesterol lowering effect, may play a role in prevention of diabetic complications. Clinical relevance of this effect of fluvastatin seems worthy of further studies.
糖尿病治疗的主要目标之一是预防其并发症。氧化应激在糖尿病中普遍存在,最终与并发症的发生有关。由于高血糖,各种组织中会产生活性氧/氮物质,导致脂质过氧化和蛋白质氧化,以及细胞内稳态破坏和受损分子积累,从而导致组织损伤。因此,补充抗氧化化合物可能对预防糖尿病并发症提供一些保护。他汀类药物的多效作用,包括抗氧化和抗炎特性,是预防和治疗心血管和神经疾病的一个非常关注的领域。本研究使用氧化应激的生物标志物,研究了非降胆固醇剂量、长期氟伐他汀治疗对链脲佐菌素诱导的糖尿病大鼠氧化应激的影响。实验在 24 只 Wistar 成年雄性大鼠中进行。糖尿病和非糖尿病大鼠在链脲佐菌素(55mg/kg,ip)注射后一周开始,每天口服给予氟伐他汀(2mg/kg/天,po),连续 6 个月(预防研究)。在大脑、心脏、肝脏、胰腺和肾脏匀浆中测量丙二醛、脂质过氧化物、蛋白质羰基含量、高级氧化蛋白产物、3-硝基酪氨酸水平和超氧化物歧化酶、过氧化氢酶活性。氟伐他汀治疗后,糖尿病组的高血糖和血脂异常仍未改变。该药物在组织中具有抗氧化作用。因此,氟伐他汀的抗氧化特性,独立于降胆固醇作用,可能在预防糖尿病并发症中发挥作用。氟伐他汀的这种作用的临床意义似乎值得进一步研究。