Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho

被引：41

作者：

Ko, Je-Won ^{[1
]}

Shin, Na-Rae ^{[1
]}

Jung, Tae-Yang ^{[1
]}

Shin, In-Sik ^{[1
]}

Moon, Changjong ^{[1
]}

Kim, Sung-Ho ^{[1
]}

Lee, In-Chul ^{[2
]}

Kim, Sung-Hwan ^{[3
]}

Yun, Won-Kee ^{[4
]}

Kim, Hyoung-Chin ^{[4
]}

Kim, Jong-Choon ^{[1
]}

机构：

[1] Chonnam Natl Univ, BK21 Plus Project Team, Coll Vet Med, 77 Yongbong Ro, Gwangju 61186, South Korea

[2] Korea Res Inst Biosci & Biotechnol, Nat Prod Res Ctr, Jeongeup 56212, South Korea

[3] Korea Inst Toxicol, Jeonbuk Dept Inhalat Res, Jeongeup 53212, South Korea

[4] Korea Res Inst Biosci & Biotechnol, Lab Anim Resource Ctr, Cheongju, South Korea

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2019年 / 129卷

基金：

新加坡国家研究基金会;

关键词：

Cisplatin; Acute kidney injury; Melatonin; Protective effect; Klotho; OXIDATIVE STRESS; INDUCED NEPHROTOXICITY; MOLECULAR-MECHANISMS; RENAL DAMAGE; APOPTOSIS; REPERFUSION; CELLS; GENE; SUPPRESSION; GLUTATHIONE;

D O I：

10.1016/j.fct.2019.04.049

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

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.

引用

页码：201 / 210

页数：10

共 55 条

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