Montilla P L, Túnez I F, Muñoz de Agueda C, Gascón F L, Soria J V
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Córdoba, Spain.
J Pineal Res. 1998 Sep;25(2):86-93. doi: 10.1111/j.1600-079x.1998.tb00544.x.
We have studied the effects of melatonin and retinol palmitate (RP) on the nephropathy and oxidative stress induced by a single and high dose of adriamycin (AD) in Wistar male rats. A dose of melatonin (75 microg/kg/day) and a dose of RP (0.25 g oily solution/kg/day, s.c.) were injected 3 and 9 days before and after the administration of AD (25 mg/kg, i.p.), respectively. After the decapitation, samples were taken from the neck vascular trunk in order to determine the triglycerides, total cholesterol, phospholipids, HDL-cholesterol, total proteins, urea, lipoperoxides, and reduced glutathione (GSH). We estimated the lipoperoxide and glutathione (GSH) contents in renal homogenates, and the excretion of proteins in urine over a 24 hr period. The administration of AD caused significant increases in proteinuria and in the other parameters studied [lipids (triglycerides, total cholesterol, phospholipids, and HDL-cholesterol), non-protein nitrogen compounds, and lipoperoxides]. AD increased the lipoperoxide content, but it decreased the GSH content in the kidney. Both melatonin and RP, although melatonin more significantly, decreased the intensity of the changes produced by the administration of AD alone. In fact, melatonin was quite efficient in reducing the formation of lipoperoxides, restoring renal GSH content and decreasing remarkably the severity of proteinuria. These results support the powerful antioxidant action of melatonin at renal level and a lower antioxidant action of retinol. Likewise, these data reinforce the hypothesis which supports the pathogenetic role and the close relation between the oxidative stress and the expression of the nephropathy induced by AD. However, in spite of this obvious antioxidant effect of melatonin in the kidney, additional studies are required to establish accurately the role of this pineal indole in the regulation and dynamics of the antioxidative defense enzyme system, which neutralizes the damaging effect of free radicals, both endogenous and exogenous, in this organ.
我们研究了褪黑素和棕榈酸视黄酯（RP）对Wistar雄性大鼠单次高剂量阿霉素（AD）诱导的肾病和氧化应激的影响。分别在给予AD（25mg/kg，腹腔注射）前3天和后9天，皮下注射剂量为75μg/kg/天的褪黑素和剂量为0.25g油溶液/kg/天的RP。断头后，从颈部血管主干采集样本，以测定甘油三酯、总胆固醇、磷脂、高密度脂蛋白胆固醇、总蛋白、尿素、脂过氧化物和还原型谷胱甘肽（GSH）。我们估计了肾匀浆中的脂过氧化物和谷胱甘肽（GSH）含量，以及24小时内尿中蛋白质的排泄量。给予AD导致蛋白尿以及所研究的其他参数[脂质（甘油三酯、总胆固醇、磷脂和高密度脂蛋白胆固醇）、非蛋白氮化合物和脂过氧化物]显著增加。AD增加了肾脏中的脂过氧化物含量，但降低了GSH含量。褪黑素和RP都能减轻单独给予AD所产生的变化强度，尽管褪黑素的作用更显著。事实上，褪黑素在减少脂过氧化物形成、恢复肾脏GSH含量以及显著降低蛋白尿严重程度方面非常有效。这些结果支持了褪黑素在肾脏水平具有强大的抗氧化作用，而视黄醇的抗氧化作用较弱。同样，这些数据强化了支持氧化应激与AD诱导的肾病表达之间的致病作用和密切关系的假说。然而，尽管褪黑素在肾脏中具有明显的抗氧化作用，但仍需要进一步研究来准确确定这种松果体吲哚在调节和动态抗氧化防御酶系统中的作用，该系统可中和内源性和外源性自由基对该器官的损害作用。
