Barangi Samira, Asadi Rouzchehr, Mehri Soghra, Karimi Gholamreza
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Toxicol Ind Health. 2023 May;39(5):248-257. doi: 10.1177/07482337231166491. Epub 2023 Apr 6.
Benzo(a)pyrene is a ubiquitous environmental contaminant, which could induce renal injury. It is reported that melatonin has a protective effect against multiple organ injuries by regulating oxidative stress, apoptosis, and autophagy. The aim of this study was to estimate the melatonin effects on benzo(a)pyrene renal toxicity in mice and the possible molecular mechanisms involved in this model. Thirty male mice were allocated to five groups and treated with benzo(a)pyrene (75 mg/kg, oral gavage) and/or melatonin (10 and 20 mg/kg, intraperitoneally). The oxidative stress factors were evaluated in renal tissue. The levels of apoptotic (the Bax/Bcl-2 ratio and caspase-3) and autophagic (the LC3 II/I, Beclin-1, and Sirt1) proteins were examined using Western blot. Following the administration of benzo(a)pyrene, malondialdehyde, caspase-3 and the Bax/Bcl-2 ratio increased in renal tissue, while Sirt1, Beclin-1, and the LC3 II/I ratio diminished. Interestingly, the co-administration of 20 mg/kg melatonin along with benzo(a)pyrene reduced the oxidative stress markers, apoptotic and autophagic proteins. Collectively, melatonin exhibited a protective effect against benzo(a)pyrene-induced renal injury through the suppression of oxidative stress and apoptosis and the inhibition of Sirt1/autophagy pathway.
苯并(a)芘是一种普遍存在的环境污染物,可导致肾损伤。据报道,褪黑素通过调节氧化应激、细胞凋亡和自噬对多器官损伤具有保护作用。本研究的目的是评估褪黑素对小鼠苯并(a)芘肾毒性的影响以及该模型中可能涉及的分子机制。将30只雄性小鼠分为五组,分别用苯并(a)芘(75mg/kg,灌胃)和/或褪黑素(10mg/kg和20mg/kg,腹腔注射)进行处理。评估肾组织中的氧化应激因子。使用蛋白质印迹法检测凋亡蛋白(Bax/Bcl-2比值和caspase-3)和自噬蛋白(LC3 II/I、Beclin-1和Sirt1)的水平。给予苯并(a)芘后,肾组织中丙二醛、caspase-3和Bax/Bcl-2比值升高,而Sirt1、Beclin-1和LC3 II/I比值降低。有趣的是,20mg/kg褪黑素与苯并(a)芘联合给药可降低氧化应激标志物、凋亡蛋白和自噬蛋白水平。总体而言,褪黑素通过抑制氧化应激和细胞凋亡以及抑制Sirt1/自噬途径对苯并(a)芘诱导的肾损伤具有保护作用。