Association of urinary chlorpyrifos, paraquat, and cyproconazole levels with the severity of fatty liver based on MRI

Environmental chemicals, such as pesticides, have become a growing concern for human health because several health issues common non-communication diseases, including obesity and type 2 diabetes are attributed to these pesticides [1, 2]. Humans are more and more exposed to pesticides through food intake, accidental or occupational exposure during farming, contacting livestock treated with insecticides, and contaminated drinking water [3]. Despite the excessive use of pesticides is reduced, over 4 billion pounds of pesticides have been used on crops annually worldwide [4]. In China, the overuse of pesticides and the toxic residues of pesticides left in water pose great health risks to families in certain areas [5, 6]. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers [7], Alzheimer [8], Parkinson [9], asthma [10], bronchitis [11], infertility [12], birth defects [13], autism [14], diabetes [15], and obesity [16]. Thus, understanding the relationship between chronic exposure to pesticides and human diseases becomes necessary.

Fatty liver is generally divided into alcoholic fatty liver diseases, non-alcoholic fatty liver diseases and metabolic dysfunction-associated fatty liver disease [17‐19]. And The incidence of FLD increased in recent years [20]. With the rapid development of medical imaging such as ultrasound, computed tomography, or MRI, the understanding of fatty infiltration of the liver is becoming more and more objective [21]. However, these imaging examinations still presented some disadvantages including operator-dependent and subjective [22], slight lack of accuracy and risks of radiation exposure [23]. Moreover, they also tend to be costly and time consuming. Beyond that, in the era of life-omics, huge amounts of multi-omics data have been generated and widely used in diagnosis of FLD [24] such as radiomics analysis [25], proteomics [26], glycomics [27], lipidomics [28], metabolomics [29]. However, characteristics of exposomes which could reflect the impact of environmental pollution have not been studied. Therefore, combining exposomes and medical imaging diagnosis would provide a potential noninvasive, time-saving, and relatively simple tool to diagnosis of FLD.

As the largest solid organ, the liver serves as a pivotal role in metabolism including lipid and glucose metabolism as well as detoxication in the human body [30]. It reported that insecticides are easily deposited in the liver and adipose tissue which led to further long-term exposure to insecticides [31]. Chlorpyrifos is one of the predominantly used pesticides to kill mosquitoes, borers, cotton aphids, and pink bollworms which were likely to damage crops like wheat, rice, and cotton [32]. However, the massive use of chlorpyrifos affects soil fertility, modifies soil microbial community structure, and poses potential health risks to non-target organisms. Chlorpyrifos mainly causes inhibition of acetylcholinesterase enzyme and damages the nervous system of humans as well as the immune system, endocrine disruption, and embryonic disorders [33‐35]. It was also reported that chlorpyrifos inhibits diet-induced thermogenesis in brown adipose tissue and this important factor contributing to the development of obesity and insulin resistance [36]. Paraquat is a cheap and effective herbicide widely used worldwide to remove weeds in vegetables, fruits, and cultivated crop fields [37]. Like with chlorpyrifos, paraquat can also cause soil and water pollution, and pose serious harm to the environment and organisms. Accidental or intentional ingestion of paraquat led to multiorgan failure through spreading to the lung, liver, kidney, thyroid gland and muscle through blood circulation is responsible for the death of paraquat poisoning [38]. Cyproconazole, developed in 1987, is a kind of triazole fungicide with the effect of anti-bacteria and plant growth regulators. It is typically applied as foliar sprays to restrain diseases by inhibiting fungal steroid demethylation [39]. Due to stability and solubility in water, cyproconazole piles up in the water and then causes harm to the human body [40]. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. It was reported that exposure to cyproconazole induces adipogenesis while repressing skeletal development based on whole-embryo transcriptomics [41]. However, there are no published reports about the relationship between the accumulation of these three commonly used pesticides and FLD progression. Thus, exploring the relationship with the progress of FLD by detecting the concentration of these three pesticides in the human body could provide new ideas for the treatment and diagnosis of FLD.

Fuyang, neighboring Henan Province and located in the northwest of the Anhui Province, is a city that mainly developed on the primary industry (agriculture, forestry, animal husbandry, and fishery). Therefore, it is unquestionable that pesticide was under extensive use and residents are easily subject to environmental exposure to pesticide residues. Thus, effective and precise detection of pesticide accumulations in the bodies of residents may also provide important suggestions for health management.

In this study, we detected three common pesticides (chlorpyrifos, paraquat, and cyproconazole) in the urine based on LC-MS. Therefore, the objective of the present study was to provide baseline information on the levels of chlorpyrifos, paraquat, and cyproconazole in urine samples from residents living in Fuyang City and to assess the correlation between the level of pesticides exposure and the severity of FLD. More importantly, this study will provide a new reference direction for the diagnosis, prevention, and treatment of FLD as well as providing suggestions for environmental protection policies.