Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho
Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho
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DOI：
10.1016/j.fct.2019.04.049
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Kim, Jong-Choon
中科院分区：
文献类型：
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作者：
Ko, Je-Won;Shin, Na-Rae;Kim, Jong-Choon
本研究探讨褪黑素(MT)对顺铂(CP)所致大鼠急性肾损伤的保护作用及其与抗衰老蛋白Klotho的可能作用机制。实验分为4组：空白对照组、CP(7 mg/kg)组、CP+MT20(20 mg/kg/d)组和CP+MT40(40 mg/kg/d)组。同时给予MT可显著改善CP诱导的大鼠急性肾损伤，表现为肾重增加，血清尿素氮和肌酐水平升高，肾小管细胞凋亡的组织病理学改变发生率增加。此外，MT处理可保护肾组织免受氧化损伤，并显著上调CP处理后Klotho的表达水平，导致蛋白激酶B(AKT)和叉头盒O(FOXO)的磷酸化水平降低，B细胞淋巴瘤相关X蛋白(Sax)和caspase-3的表达水平降低。MT不仅通过AKT/FOXO信号通路部分调节氧化应激，而且通过抑制Bax/caspase-3通路减少CP诱导的细胞凋亡。结果表明，MT可能通过上调Klotho的表达，从而提高抗氧化和抗细胞凋亡能力，从而预防CP所致的大鼠急性肾损伤。
This study investigated the protective effects of melatonin (MT) against cisplatin (CP)-induced acute kidney injury in rats as well as its possible mechanism of action associated with anti-aging protein Klotho. The following four experimental groups were evaluated: vehicle control, CP (7 mg/kg), CP&MT20 (20 mg/kg/day), and CP& MT40 (40 mg/kg/day). The concomitant administration of MT significantly ameliorated CP-induced acute kidney injury in rats, as evidenced by increased kidney weight, increased serum levels of blood urea nitrogen and creatinine, and increased incidence of histopathological alterations with renal tubular cell apoptosis. In addition, MT treatment protected kidney tissue against oxidative damages and significantly upregulated the expression level of Klotho decreased by CP treatment, resulting in reduced phosphorylation of protein kinase B (AKT) and forkhead box O (FOXO) as well as reduced expression levels of B-cell lymphoma 2-associated X protein (Sax) and caspase-3. MT not only partially regulated oxidative stress via AKT/FOXO signaling, but also reduced apoptosis caused by CP by inhibiting the Bax/caspase-3 pathway. Our results indicated that MT could prevent acute kidney injury induced by CP in rats, presumably through upregulating the expression of Klotho, resulting in elevated anti-oxidant and anti-apoptotic properties.