O'Brien Peter J, Siraki Arno G, Shangari Nandita
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Crit Rev Toxicol. 2005 Aug;35(7):609-62. doi: 10.1080/10408440591002183.
Aldehydes are organic compounds that are widespread in nature. They can be formed endogenously by lipid peroxidation (LPO), carbohydrate or metabolism ascorbate autoxidation, amine oxidases, cytochrome P-450s, or myeloperoxidase-catalyzed metabolic activation. This review compares the reactivity of many aldehydes towards biomolecules particularly macromolecules. Furthermore, it includes not only aldehydes of environmental or occupational concerns but also dietary aldehydes and aldehydes formed endogenously by intermediary metabolism. Drugs that are aldehydes or form reactive aldehyde metabolites that cause side-effect toxicity are also included. The effects of these aldehydes on biological function, their contribution to human diseases, and the role of nucleic acid and protein carbonylation/oxidation in mutagenicity and cytotoxicity mechanisms, respectively, as well as carbonyl signal transduction and gene expression, are reviewed. Aldehyde metabolic activation and detoxication by metabolizing enzymes are also reviewed, as well as the toxicological and anticancer therapeutic effects of metabolizing enzyme inhibitors. The human health risks from clinical and animal research studies are reviewed, including aldehydes as haptens in allergenic hypersensitivity diseases, respiratory allergies, and idiosyncratic drug toxicity; the potential carcinogenic risks of the carbonyl body burden; and the toxic effects of aldehydes in liver disease, embryo toxicity/teratogenicity, diabetes/hypertension, sclerosing peritonitis, cerebral ischemia/neurodegenerative diseases, and other aging-associated diseases.
醛是自然界中广泛存在的有机化合物。它们可通过脂质过氧化（LPO）、碳水化合物或代谢性抗坏血酸自氧化、胺氧化酶、细胞色素P-450或髓过氧化物酶催化的代谢活化在内源性形成。本综述比较了许多醛对生物分子尤其是大分子的反应性。此外，它不仅包括环境或职业相关的醛，还包括膳食醛以及由中间代谢内源性形成的醛。还包括作为醛或形成具有副作用毒性的反应性醛代谢物的药物。综述了这些醛对生物学功能的影响、它们对人类疾病的贡献，以及核酸和蛋白质羰基化/氧化分别在致突变性和细胞毒性机制中的作用，以及羰基信号转导和基因表达。还综述了醛通过代谢酶的代谢活化和解毒作用，以及代谢酶抑制剂的毒理学和抗癌治疗作用。综述了临床和动物研究中的人类健康风险，包括醛在过敏性超敏反应疾病、呼吸道过敏和特异质性药物毒性中作为半抗原的情况；羰基体负荷的潜在致癌风险；以及醛在肝病、胚胎毒性/致畸性、糖尿病/高血压、硬化性腹膜炎、脑缺血/神经退行性疾病和其他与衰老相关疾病中的毒性作用。
