Parlakpinar Hakan, Sahna Engin, Ozer M K, Ozugurlu Fikret, Vardi Nigar, Acet Ahmet
Department of Pharmacology, Faculty of Medicine, Inonu University, Malatya, Turkey.
J Pineal Res. 2002 Oct;33(3):161-6. doi: 10.1034/j.1600-079x.2002.02910.x.
Cisplatin [cis-diaminedichloroplatinum(II), CDDP] is a widely used antineoplastic drug. However, it has major side-effects such as acute tubular necrosis (ATN). There are a number of studies concerning the role of reactive oxygen radical species in the pathophysiology of CDDP-dependent ATN. Several antioxidant agents have been reported to prevent this side-effect but there is no study regarding the protective action of either physiological or pharmacological concentrations of melatonin. Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger and indirect antioxidant. We investigated the effects of melatonin on CDDP-induced changes of renal malondialdehyde (MDA), a lipid peroxidation product, and blood urea nitrogen (BUN) and serum creatine (Cr). The morphological changes in kidney were also examined using light microscopy. The rats were divided into two groups: pinealectomized (Px) and sham-operated (non-Px). Both CDDP and melatonin were administered to all groups. MDA levels were found to be higher in Px than non-Px animals. CDDP administration to Px or non-Px rats increased renal MDA levels and melatonin administration either before or after CDDP injection caused significant decreases in MDA in kidney compared with those in rats treated with CDDP alone. Serum levels of BUN and Cr did not change as a result of any treatment. Morphological tubule damage because of CDDP was more severe in the renal cortex than in the medulla. The damage to the kidney induced by CDDP was reversed by melatonin. The results show that pharmacological and physiological concentrations of melatonin reduce CDDP-induced renal injury.
顺铂[顺式二氨基二氯铂(II)，CDDP]是一种广泛使用的抗肿瘤药物。然而，它有诸如急性肾小管坏死(ATN)等主要副作用。有许多关于活性氧自由基在顺铂依赖性急性肾小管坏死病理生理学中作用的研究。据报道，几种抗氧化剂可预防这种副作用，但尚无关于生理或药理浓度褪黑素保护作用的研究。褪黑素是松果体的主要分泌产物，是一种直接的自由基清除剂和间接抗氧化剂。我们研究了褪黑素对顺铂诱导的肾脂质过氧化产物丙二醛(MDA)、血尿素氮(BUN)和血清肌酐(Cr)变化的影响。还使用光学显微镜检查了肾脏的形态学变化。将大鼠分为两组：松果体切除组(Px)和假手术组(非Px)。所有组均给予顺铂和褪黑素。发现Px组动物的MDA水平高于非Px组。给Px或非Px大鼠注射顺铂会增加肾脏MDA水平，与单独用顺铂治疗的大鼠相比，在顺铂注射前或后给予褪黑素可使肾脏MDA显著降低。任何治疗均未导致血清BUN和Cr水平发生变化。顺铂引起的形态学肾小管损伤在肾皮质比在髓质更严重。褪黑素可逆转顺铂对肾脏的损伤。结果表明，药理和生理浓度的褪黑素可减轻顺铂诱导的肾损伤。
