Abdel-Wahab M H, Abd-Allah A R
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr-City, Cairo, Egypt.
Pharmacol Res. 2000 May;41(5):533-7. doi: 10.1006/phrs.1999.0614.
There is a clear link between diabetes and oxidative stress. Hyperglycaemia leads to free radical generation and alteration of endogenous antioxidants. The present study is an attempt to evaluate the possible protective effect of melatonin (MLT) and/or desferrioxamine (DF) against streptozotocin (STZ)-induced hyperglycaemia in mice. Serum lipid profile, pancreatic tissue contents of glutathione (GSH) and malondialdehyde (MDA) were determined. MLT and/or DF were given p.o. in doses of 5 mg kg(-1)day(-1)and 250 mg kg(-1) day(-1), respectively for 15 consecutive days prior to STZ treatment (60 mg kg(-1) day(-1) i.p.) for 3 consecutive days. Results revealed that STZ induced a marked increase in serum glucose, serum triglycerides (TG), cholesterol (CHO) and LDL-cholesterol. On the contrary HDL-cholesterol was markedly decreased in STZ-treated group. Moreover, STZ induced a significant decrease in the pancreatic content of GSH with concomitant increase in MDA content. Administration of MLT or (MLT+DF) prior to STZ treatment revealed a marked decrease in serum glucose level by 35.6 and 31.6%, respectively as compared to STZ-treated group. Furthermore, MLT pretreatment of STZ-induced hyperglycemic mice, has not only normalized GSH content of pancreatic tissues but also increased its level more than that of control animals by 110%. On the contrary, MDA content of pancreatic tissues was markedly decreased even lower than normal control group. MLT also, induced a marked protection in terms of decreasing serum CHO, LDL, TG by 21.8, 83.8 and 82.2%, respectively, while HDL was increase by 56% as compared to STZ treated group. DF was found to be less effective than MLT in the protection against STZ-induced hyperglycemia. In conclusion, these data suggest that MLT protects against the damaging consequences induced by hyperglycemia either systemically or in the pancreatic tissues.
糖尿病与氧化应激之间存在明显联系。高血糖会导致自由基生成以及内源性抗氧化剂的改变。本研究旨在评估褪黑素（MLT）和/或去铁胺（DF）对链脲佐菌素（STZ）诱导的小鼠高血糖可能具有的保护作用。测定了血清脂质谱、胰腺组织中谷胱甘肽（GSH）和丙二醛（MDA）的含量。在STZ治疗（腹腔注射60 mg kg⁻¹ day⁻¹，连续3天）前连续15天分别以5 mg kg⁻¹ day⁻¹和250 mg kg⁻¹ day⁻¹的剂量口服给予MLT和/或DF。结果显示，STZ导致血清葡萄糖、血清甘油三酯（TG）、胆固醇（CHO）和低密度脂蛋白胆固醇显著升高。相反，STZ治疗组的高密度脂蛋白胆固醇显著降低。此外，STZ导致胰腺组织中GSH含量显著降低，同时MDA含量增加。在STZ治疗前给予MLT或（MLT + DF），与STZ治疗组相比，血清葡萄糖水平分别显著降低了35.6%和31.6%。此外，对STZ诱导的高血糖小鼠进行MLT预处理，不仅使胰腺组织的GSH含量恢复正常，还使其水平比对照动物高出110%。相反，胰腺组织的MDA含量显著降低，甚至低于正常对照组。与STZ治疗组相比，MLT还分别使血清CHO、LDL、TG显著降低了21.8%、83.8%和82.2%，而HDL升高了56%。发现DF在预防STZ诱导的高血糖方面不如MLT有效。总之，这些数据表明MLT可保护机体免受高血糖在全身或胰腺组织中引起的破坏性后果。
