Hünkar Tuğba, Aktan Fugen, Ceylan Asli, Karasu Cimen
Department of Pharmacology, Faculty of Pharmacy, Ankara University, 06100 Tandoğan, Ankara, Turkey.
Cell Biochem Funct. 2002 Dec;20(4):297-302. doi: 10.1002/cbf.977.
Lipid disorders and increased oxidative stress may exacerbate some complications of diabetes mellitus. Previous studies have implicated the beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the protection of cells from the destructive effect of increased lipids and lipid peroxidation products. This study, therefore, was designed to investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which comprises mainly vitamin A, PUFAs, EPA and DHA. Effects were monitored on plasma lipids, lipid peroxidation products (MDA) and the activities of antioxidant enzymes, glutathione peroxidase (GSHPx) and catalase in heart, liver, kidney and lung of non-diabetic control and streptozotocin (STZ)-induced-diabetic rats. Two days after STZ-injection (55 mg kg(-1) i.p.), non-diabetic control and diabetic rats were divided randomly into two groups as untreated or treated with CLO (0.5 ml kg(-1) rat per day) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic animals; CLO treatment almost completely prevented these abnormalities in triacylglycerol and cholesterol, but hyperglycaemia was partially controlled. CLO also provided better weight gain in diabetic animals. In untreated diabetic rats, MDA markedly increased in aorta, heart and liver but was not significantly changed in kidney and lung. This was accompanied by a significant increase in both GSHPx and catalase enzyme activities in aorta, heart, and liver of diabetic rats. In kidney and lung, diabetes resulted in reduced catalase while GSHPx was significantly activated. In aorta, heart, and liver, diabetes-induced changes in MDA were entirely prevented by CLO treatment. In the tissues of CLO-treated diabetic animals, GSHPx activity paralleled those of control animals. CLO treatment also caused significant improvements in catalase activities in every tissue of diabetic rats, but failed to affect MDA and antioxidant activity in control animals. The current study suggests that the treatment of diabetic rats with CLO provides better control of glucose and lipid metabolism, allows recovery of normal growth rate, prevents oxidative/peroxidative stress and ameliorates endogenous antioxidant enzyme activities in various tissues. Because CLO contains a plethora of beneficial compounds together, its use for the management of diabetes-induced complications may provide important advantages.
脂质紊乱和氧化应激增加可能会加剧糖尿病的一些并发症。先前的研究表明,某些抗氧化剂、ω-3多不饱和脂肪酸(PUFA)、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)对保护细胞免受脂质增加和脂质过氧化产物的破坏作用具有有益效果。因此,本研究旨在调查主要由维生素A、PUFA、EPA和DHA组成的鱼肝油(CLO,Lysi Ltd. Island)的作用。对非糖尿病对照大鼠和链脲佐菌素(STZ)诱导的糖尿病大鼠的心脏、肝脏、肾脏和肺中的血浆脂质、脂质过氧化产物(MDA)以及抗氧化酶谷胱甘肽过氧化物酶(GSHPx)和过氧化氢酶的活性进行了监测。在STZ注射(55 mg kg⁻¹腹腔注射)两天后,将非糖尿病对照大鼠和糖尿病大鼠随机分为两组,一组不进行处理,另一组用CLO(每天0.5 ml kg⁻¹大鼠)处理12周。在未经处理的12周糖尿病动物中,血浆葡萄糖、三酰甘油和胆固醇浓度显著升高;CLO处理几乎完全预防了三酰甘油和胆固醇的这些异常,但高血糖仅得到部分控制。CLO还使糖尿病动物的体重增加得更好。在未经处理的糖尿病大鼠中,主动脉、心脏和肝脏中的MDA显著增加,但肾脏和肺中的MDA没有显著变化。与此同时,糖尿病大鼠的主动脉、心脏和肝脏中的GSHPx和过氧化氢酶活性均显著增加。在肾脏和肺中,糖尿病导致过氧化氢酶减少,而GSHPx被显著激活。在主动脉、心脏和肝脏中,CLO处理完全预防了糖尿病引起的MDA变化。在接受CLO处理的糖尿病动物的组织中,GSHPx活性与对照动物的相似。CLO处理还使糖尿病大鼠各组织中的过氧化氢酶活性有显著改善,但对对照动物的MDA和抗氧化活性没有影响。当前研究表明,用CLO治疗糖尿病大鼠可更好地控制葡萄糖和脂质代谢,使正常生长速率恢复,预防氧化/过氧化应激,并改善各种组织中的内源性抗氧化酶活性。由于CLO含有大量有益化合物,其用于治疗糖尿病引起的并发症可能具有重要优势。