Melatonin attenuates cisplatin-induced acute kidney injury in mice: Involvement of PPARα and fatty acid oxidation. (May 2022)

• Record Type: Journal Article
• Authors: Sun, Tao; Wang, Di; Wang, Baoying; Liu, Xianghua; Li, Ningning; Shi, Ke
• Is Part Of: Food and chemical toxicology. Volume 163(2022)
• Publication Date: 2022-05
• Subjects: Cisplatin -- Acute kidney injury -- Melatonin -- Fatty acid oxidation -- PPARα; Bax B-cell lymphoma 2-associated X protein -- BUN blood urea nitrogen -- CPT1 carnitine O-palmitoyltransferase 1 -- FAO fatty acid oxidation -- H&E hematoxylin and eosin -- IHC immunohistochemistry -- NF-kB nuclear factor-kappa B -- PGC-1α peroxidase proliferative agent activation receptor co-activator-1α -- PPARα peroxidase proliferative receptor α -- RAS renin-angiotensin system -- SEM standard error of the mean -- SCr serum creatinine -- TG triglyceride -- TUNEL Terminal deoxynucleotidyl transferasemediated dUTP-end labeling; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.112970
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: The present study focused on the protective effects of melatonin against cisplatin-induced acute kidney injury in mice and its possible mechanism of action in relation to the major regulator of fatty acid oxidation (FAO), peroxidase proliferative receptor α (PPARα). The experiment consisted of the following four groups: vehicle control, cisplatin (15 mg/kg), cisplatin & melatonin (20 mg/kg/day), and melatonin (20 mg/kg/day). Concomitant administration of melatonin significantly ameliorated cisplatin-induced acute kidney injury in mice by decreasing serum levels of triglyceride, blood urea nitrogen and creatinine, reducing the number and size of lipid droplets in tubular epithelial cells, and decreasing the incidence of histopathological changes including tubular cell apoptosis. Moreover, melatonin administration protected kidney tissue by significantly upregulating the levels of PPARα reduced by cisplatin injection, resulting in increased FAO pathway-associated genes (PGC-1a, Acadm, Acat1, Acsm2, Acsm3, Bdh2, Echs and Pecr) as well as reducing protein levels of caspase-3, -9 and Bax. Melatonin not only partially modulated FAO via PPARα signaling, but also decreased cisplatin-induced apoptosis by inhibiting the caspase-3, -9 and Bax pathways. Our findings suggest that melatonin prevents cisplatin-induced acute kidney injury in mice, possibly by upregulating the expression of PPARα, resulting in enhanced FAO and anti-apoptotic properties. Highlights: Melatonin ameliorated both renal function and histopathologic alterations of cisplatin-induced acute kidney injury in mice. Melatonin partially regulated fatty acid oxidation in renal tubular epithelial cell via PPARα signal pathway. Melatonin reduced apoptosis caused by cisplatin by inhibiting the caspase-3, 9 and Bax pathway.