Pesticides in mixture disrupt metabolic regulation: In silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice

作者：Bhaskar Rakesh; Mohanty B****ata^*

来源：General and Comparative Endocrinology, 2014, 205: 226-234.

DOI：10.1016/j.ygcen.2014.02.007

• Pesticide
• Thyroid axis disruption
• Molecular docking
• TR
• PPAR gamma

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TR alpha and TR beta) and peroxisome proliferator activated receptor gamma (PPAR gamma), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T-3, and its antagonist ethylene thiourea (ETU) as well as PPAR gamma agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T-3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPAR gamma, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPAR gamma. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight.

• 出版日期2014-9-1