Toxic Effects of Endocrine Disruptor Exposure on Collagen-Induced Arthritis
Ramona D'Amico1, Enrico Gugliandolo2, Marika Cordaro3
1Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.
Abstract:
Endocrine disruptors (EDs) are chemical substances capable of affecting endocrine system functioning and interfering with organ morphogenesis and physiological functions. The development and regeneration of bone tissues have a complex hormonal regulation, and therefore, bone tissue cells can be considered potential targets for endocrine disruptors. In that regard, the aim of this research was to investigate the impact of ED exposure on the inflammatory response and oxidative stress in an experimental model of collagen-induced arthritis (CIA). Arthritis was induced by an emulsion of type II collagen (CII) and complete Freund's adjuvant, which was administered intradermally on days 0 and 21. Mice from day 21 to day 35 received the following EDs by oral gavage: cypermethrin (CP), diethyl phthalate (DEP), vinclozolin (VCZ), 17α-ethinylestradiol (EE), perfluorooctanesulfonic acid (PFOS) and atrazine (ATR). ED exposure caused worsening of clinical signs (erythema and edema in the hind paws), histological and radiographic changes, as well as behavioral deficits, induced by CII injections. Furthermore, ED exposure significantly increased the degree of inflammation and oxidative damage induced by arthritis; this upregulation was more evident after exposure to ATR than to other EDs. The results from our study suggest that exposure to EDs may play a deleterious role in the progression of RA; therefore, exposure to EDs should be limited.
Insights
Endocrine disruptors (EDs) worsen arthritis symptoms and increase inflammation and oxidative stress. Limiting exposure to these chemicals is recommended to mitigate their harmful effects on rheumatoid arthritis progression.
Area of Science:
- Endocrinology
- Toxicology
- Immunology
Background:
- Bone tissue development and regeneration are hormonally regulated, making bone cells potential targets for endocrine disruptors (EDs).
- Collagen-induced arthritis (CIA) is an experimental model used to study inflammatory arthritis.
- EDs can interfere with endocrine system functioning and physiological processes.
Purpose of the Study:
- To investigate the impact of ED exposure on inflammatory response and oxidative stress in a CIA mouse model.
- To assess the effects of specific EDs including cypermethrin, diethyl phthalate, vinclozolin, ethinylestradiol, perfluorooctanesulfonic acid, and atrazine.
Main Methods:
- Arthritis was induced in mice using type II collagen (CII) and complete Freund's adjuvant.
- Mice were orally gavaged with various EDs from day 21 to day 35 post-induction.
- Clinical signs, histological and radiographic changes, and behavioral deficits were evaluated.
Main Results:
- ED exposure exacerbated clinical signs, histological, radiographic, and behavioral deficits associated with CIA.
- EDs significantly increased inflammation and oxidative damage in arthritic mice.
- Atrazine (ATR) exposure showed a more pronounced upregulation of inflammation and oxidative stress compared to other EDs.
Conclusions:
- ED exposure plays a deleterious role in the progression of rheumatoid arthritis (RA).
- Exposure to EDs should be limited to prevent worsening of RA.
- EDs can negatively impact bone health and immune responses relevant to arthritis.
Related Concept Videos
01:26Toxic Reactions: Overview
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
01:23Rheumatic Heart Disease I: Introduction
01:20The JAK-STAT Signaling Pathway