NADPH Oxidase Inhibitor Apocynin Attenuates PCB153-Induced Thyroid Injury in Rats.

Ablikim Abliz,Wenhong Deng,Weixing Wang,Rongze Sun,Chen Chen

doi:10.1155/2016/8354745

Ablikim Abliz, Wenhong Deng + Show 3 more

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https://doi.org/10.1155/2016/8354745

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Abstract

PCBs, widespread endocrine disruptors, cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. However, the exact mechanism of thyroid dysfunction caused by PCBs is still unknown. In order to clarify the hypotheses that NADPH oxidase (NOX) and subsequent NF-κB pathway may play roles in thyroid dysfunction, sixty Sprague-Dawley rats were randomly divided into four groups: control group, PCB153 treated (PCB) group, received apocynin with PCB153 treatment (APO + PCB) group, and drug control (APO) group. Serum thyroid hormone levels were evaluated. The morphological change of thyroid tissue was analyzed under the light and transmission electron microscopy. NOX2, 8-OHdG, and NF-κB expression in the thyroid tissue was evaluated by immune-histochemical staining. Oxidative stress and inflammatory cytokines were detected. The following results were reduced after apocynin treatment: (1) serum thyroid hormone, (2) thyroid pathological injuries, (3) thyroid MDA, (4) thyroid ultrastructural change, (5) serum inflammatory cytokines, and (6) thyroid expression of NOX2, 8-OHdG, and NF-κB. These results suggested that NOX inhibition attenuates thyroid dysfunction induced by PCB in rats, presumably because of its role in preventing ROS generation and inhibiting the activation of NF-κB pathway. Our findings may provide new therapeutic targets for PCBs induced thyroid dysfunction.

Highlights

Polychlorinated biphenyls (PCBs) are a type of typical and widespread environmental endocrine disruptors which has been used in many industries
The results of the current study demonstrate that exposure to PCB153 could severely damage thyroidal structure, dramatically decreasing the concentration of serum thyroid hormones
Pretreatment with the NADPH oxidase (NOX) inhibitor apocynin attenuates (1) serum thyroid hormone (TH) level; (2) morphological change of thyroid follicles; (3) ultrastructural change of thyroid follicular cells; (4) proinflammatory cytokine production; (5) MDA; (6) expression of NOX2, NF-κB, and 8-OHdG. All of these observations suggest that NOX may participate in the process of thyroid dysfunction induced by PCB153 and treatment with NOX inhibition by apocynin exerts potent anti-inflammatory and antioxidative

Summary

Introduction

Polychlorinated biphenyls (PCBs) are a type of typical and widespread environmental endocrine disruptors which has been used in many industries. A large number of PCBs still exist in the environment due to their chemical stability and lipophilic properties. They affect human health by damaging multiple organs because of accumulating in adipose tissue and biomagnification in the food chain. PCBs have received wide attention due to their multiple range adverse effects on human health including hepatotoxicity, reproductive toxicity, developmental toxicity, immune suppression, carcinogenicity, and endocrine disruption such as the disruption of thyroid hormone (TH) homeostasis [1,2,3,4]. It is obvious that PCBs could interfere with thyroid hormone synthesis, secretion, transportation, and metabolism. Some researchers suggest that PCB153 could eliminate the biosynthesis of THs by influencing synthesis-associated proteins, such as the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and thyroglobulin (Tg) [4]

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