Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Toxicol Appl Pharmacol. 2013 Apr 15;268(2):157-77. doi: 10.1016/j.taap.2013.01.025. Epub 2013 Feb 9.
Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action.
随着农药在世界范围内的广泛使用，人们对其健康影响的担忧也迅速增加。大量证据表明，接触农药与多种慢性疾病的高发率有关，如各种癌症、糖尿病、神经退行性疾病（如帕金森病、阿尔茨海默病和肌萎缩侧索硬化症）、出生缺陷和生殖障碍。还有一些间接证据表明，接触农药与其他一些慢性疾病有关，如呼吸道问题，特别是哮喘和慢性阻塞性肺疾病（COPD）、心血管疾病，如动脉粥样硬化和冠心病、慢性肾病、自身免疫性疾病，如系统性红斑狼疮和类风湿关节炎、慢性疲劳综合征和衰老。慢性疾病的共同特征是细胞内稳态的紊乱，这种紊乱可能是由农药的直接作用引起的，如离子通道、酶、受体等的扰动，也可能是通过主要机制以外的途径介导的。在这篇综述中，我们提出了接触农药与慢性疾病发病率之间关联的重点证据，并介绍了遗传损伤、表观遗传修饰、内分泌干扰、线粒体功能障碍、氧化应激、内质网应激和未折叠蛋白反应（UPR）、泛素蛋白酶体系统受损和自噬缺陷作为有效的作用机制。
