Melatonin attenuates cardiopulmonary toxicity induced by benzo(a)pyrene in mice focusing on apoptosis and autophagy pathways.

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon and a serious environmental pollutant. BaP is formed by the incomplete combustion of organic matter at high temperatures. In addition, tobacco smoke and many foods, especially charbroiled food and grilled meats, contain BaP and can cause it to enter human body. Melatonin, a pineal gland hormone, has antioxidant, anti-apoptosis, and autophagy regulatory properties. The possible protective impact of melatonin on cardiopulmonary toxicity induced by BaP was investigated by examining the antioxidant effects and the apoptosis and autophagy properties of melatonin. Thirty male mice were divided into 5 groups and treated for 28 days as follows: (I) control (BaP and melatonin solvent), (II) BaP (75 mg/kg, oral gavage), (III and IV) BaP (75 mg/kg) + melatonin (10 and 20 mg/kg, intraperitoneally), (V) melatonin (20 mg/kg). The oxidative stress factors (MDA and GSH content) were assessed in the heart and lung tissues. The levels of apoptotic (Caspase-3 and the Bax/Bcl-2 ratio) and autophagic (the LC3 ӀӀ/Ӏ, Beclin-1, and Sirt1) proteins were examined by using western blot analysis. Following the administration of BaP, MDA, the Bax/Bcl-2 ratio, and the Caspase-3 proteins increased in the heart and lung tissues, while GSH, Sirt1, Beclin-1, and the LC3 II/I ratio diminished. The coadministration of melatonin along with BaP, MDA, and apoptotic proteins returned to the control values, while GSH and the autophagy proteins were enhanced in both the heart and lungs. Melatonin exhibited a protective effect against BaP-induced heart and lung injury through the suppression of oxidative stress and apoptosis and the induction of the Sirt1/autophagy pathway.