Quasmi Mohammed Nazish, Kumar Dinesh, Jangra Ashok
Department of Pharmaceutical Sciences, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendragarh, India.
Toxicol Rep. 2024 Dec 10;14:101859. doi: 10.1016/j.toxrep.2024.101859. eCollection 2025 Jun.
Acrylamide (AA) has raised concerns throughout the world in recent years because of its potential negative effects on human health. Numerous researches on humans and animals have connected a high dietary exposure to AA to a possible risk of cancer. Additionally, higher consumption of acrylamide has also been associated with dysfunctioning of various organ systems from nervous system to the reproductive system. Acrylamide is primarily metabolised into the glycidamide inside the body which gets accumulated in different tissues including kidney and liver, and chronic exposure to this can lead to the nephrotoxicity and hepatotoxicity through different molecular mechanisms. This review summarizes the various sources, formation and metabolism of the dietary acrylamide along with the different molecular mechanisms such as oxidative stress, inflammation, DNA damage, autophagy, mitochondrial dysfunction and morphological changes in nephron and hepatocytes through which acrylamide exerts its deleterious effect on kidney and liver causing nephrotoxicity and hepatotoxicity. This review summarizes various animal and cellular studies that demonstrate AA-induced nephrotoxicity and hepatotoxicity. Lastly, the article emphasizes on underlying protective molecular mechanisms of various pharmacological interventions against acrylamide induced hepatotoxicity and nephrotoxicity.
近年来,丙烯酰胺(AA)因其对人类健康的潜在负面影响而引起了全球关注。众多针对人类和动物的研究已将高膳食丙烯酰胺暴露与可能的癌症风险联系起来。此外,丙烯酰胺摄入量的增加还与从神经系统到生殖系统等各种器官系统的功能失调有关。丙烯酰胺在体内主要代谢为环氧丙酰胺,它会在包括肾脏和肝脏在内的不同组织中积累,长期接触这种物质会通过不同的分子机制导致肾毒性和肝毒性。本综述总结了膳食丙烯酰胺的各种来源、形成和代谢,以及丙烯酰胺通过氧化应激、炎症、DNA损伤、自噬、线粒体功能障碍以及肾单位和肝细胞形态变化等不同分子机制对肾脏和肝脏产生有害影响,从而导致肾毒性和肝毒性。本综述总结了各种动物和细胞研究,这些研究证明了AA诱导的肾毒性和肝毒性。最后,本文强调了各种药物干预措施针对丙烯酰胺诱导的肝毒性和肾毒性的潜在保护分子机制。