Invited Review Article
Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

https://doi.org/10.1016/j.taap.2013.01.025Get rights and content

Abstract

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.

Highlights

► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.

Introduction

Pesticides are considered as one of the main factors involved in environmental contamination of today's world. These chemicals are on purpose designed to be toxic to pest and vectors of diseases. These compounds are among more than 1000 active ingredients that are marketed as insecticide, herbicide, and fungicide. Nevertheless, formulation of new and potent pesticides is increasingly on the order of researchers and manufacturers because of pest resistance, hygienic controls, and major human need for more food as the world population grows. Although pesticides have largely benefited the human life through enhancement of agricultural products and controlling infectious diseases, their extensive use, in turn, has offended human health from side to side of occupational or environmental exposures. Long-term contact to pesticides can harm human life and can disturb the function of different organs in the body, including nervous, endocrine, immune, reproductive, renal, cardiovascular, and respiratory systems. In this regard, there is mounting evidence on the link of pesticide's exposure with the incidence of human chronic diseases, including cancer, Parkinson, Alzheimer, multiple sclerosis, diabetes, aging, cardiovascular and chronic kidney disease (Abdollahi et al., 2004c, De Souza et al., 2011, Mostafalou and Abdollahi, 2012a). In this overview, we discuss the association of pesticide's exposure with the incidence of different types of human chronic diseases as well as general mechanisms of disease's process, which can be involved in pesticide-induced toxicities.

Section snippets

Evidences for the link between pesticide exposure and incidence of chronic diseases

Chronic diseases are characterized by their generally slow progression and long term duration, which are considered as the leading cause of mortality in the new world, representing over 60% of all deaths. According to the WHO report, 36 million people died from chronic disease in 2008, of which nine million were under 60 and 90% of these premature deaths occurred in low- and middle-income countries (http://www.who.int/topics/chronic_diseases/en/).

Genetic damages

Genetic damages are caused by direct interaction with genetic material resulting in DNA damage or chromosomal aberrations and considered as a primary mechanism for chronic diseases within the context of carcinogenesis and teratogenesis. They are studied in the field of genetic toxicology and can be detected by distinctive kinds of genotoxicity tests. Growing body of data concerning genetic toxicity of pesticides have been collected from epidemiological and experimental studies using different

Endocrine disruption

At a cellular level, endocrine disruption refers to a mechanism of toxicity that interferes the ability of the cells to communicate hormonally and results in a wide variety of adverse health effects including birth defects, reproductive, developmental, metabolic, immune, and neurobehavioral disorders as well as hormone dependent cancers. The term “endocrine disruptor” (ED) was first introduced in 1991 referring to the substances that interfere with synthesis, secretion, transport, binding,

Conclusion

Taken together, chronic diseases discussed above are considered as the major disorders affecting public health in the 21st century. The relationship between these diseases and environmental exposures, particularly pesticides increasingly continues to strengthen. Near to all studies carried out in the area of pesticides, and chronic diseases are categorized in the field of epidemiologic evidence or experimental investigation with mechanistic insight into the disease process. Some epidemiologic

Conflict of interest statement

There is no competing interest.

Acknowledgments

Authors wish to thank assistances of INSF and TUMS.

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