Melatonin inhibits Benzo(a)pyrene-Induced apoptosis through activation of the Mir-34a/Sirt1/autophagy pathway in mouse liver

• Autores: Barangi, Samira; Mehri, Soghra; Moosavi, Zahra; Hayesd, A Wallace; Reiter, Russel J.; Cardinali, Daniel Pedro; Karimi, Gholamreza
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Ecotoxicology and Environmental Safety. 2020, 196
• Materia: APOPTOSIS; ANTIOXIDANTES; RIÑON; MELATONINA
• Institución: Pontificia Universidad Católica Argentina

Fil: Barangi, Samira. Mashhad University of Medical Sciences. School of Pharmacy. Department of Pharmacodynamics and Toxicology; Iran
Fil: Mehri, Soghra. Mashhad University of Medical Sciences. School of Pharmacy. Department of Pharmacodynamics and Toxicology; Iran
Fil: Moosavi, Zahra. Ferdowsi University of Mashhad. Faculty of Veterinary Medicine. Department of Pathobiology; Iran
Fil: Hayesd, A Wallace. University of South Florida; Estados Unidos
Fil: Hayesd, A Wallace. Michigan State University; Estados Unidos
Fil: Reiter, Russel J. University of Texas. Health Science Center at San Antonio. Department of Cellular and Structural Biology; Estados Unidos
Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Karimi, Gholamreza. Mashhad University of Medical Sciences. School of Pharmacy. Department of Pharmacodynamics and Toxicology; Iran
Abstract: Benzo(a)pyrene (BaP), an important environmental pollutant, is produced as the result of incomplete combustion of organic materials in many industries and food cooking process. It has been purposed that BaP induces hepatotoxicity through oxidative stress and apoptosis. Several studies have shown that melatonin can protect against chemical-induced apoptosis through autophagy pathway. In this study, we assessed the modulating effect of melatonin, a well-known antioxidant, on BaP-induced hepatotoxicity through induction of autophagy. Thirty male mice were treated daily for 28 consecutive days. BaP (75 mg/kg; oral gavage) and melatonin (10 and 20 mg/kg, i.p.) were administered to mice. The liver histopathology and the levels of apoptosis and autophagy proteins as well as the expression of miR-34a were determined. The BaP exposure induced severe liver histological injury and markedly enhanced AST, ALT and MDA level. Also, apoptosis proteins and hepatic miR-34a expression increased. However, the level of Sirt1 and autophagy markers such as LC3 II/I ratio and Beclin-1 reduced. The co-administration of melatonin reversed all changes caused by BaP. In summary, melatonin appears to be effective in BaP-induced hepatotoxicity maybe through the miR-34a/Sirt1/autophagy molecular pathway.