Intervention effect of gamma aminobutyric acid on anxiety behavior induced by phthalate (2-ethylhexyl ester) in rats

ABSTRACT

Background: Di(2-ethylhexyl) phthalate (DEHP) is one of the most widely used phthalate esters. The application of DEHP has caused serious environmental pollution and posed a threat to human health.

Methods: A total of 30 male Sprague-Dawley rats were randomly divided into control group, DEHP group (500 mg/kg DEHP), low GABA (Gama-aminobutyric acid) group (500 mg/kg DEHP and 1 mg/kg GABA), medium GABA group (500 mg/kg DEHP and 2 mg/kg GABA) and high GABA group (500 mg/kg DEHP and 4 mg/kg GABA). The interventions continued for 30 consecutive days. Open-field test and elevated plus-maze test were used to detect behavioral changes of rats before and after interventions.

Results: The levels of nitric oxide and nitric oxide synthase in prefrontal cortex of rats were measured using enzyme-linked immunosorbent assay. DEHP and GABA treatment had no significant effects on the body weight of rats. GABA restored food utilization rate of rats impaired by DEHP to the level of healthy rats. According to open-field test and elevated plus-maze test, GABA alleviated the effects of DEHP on rat behaviors. Enzyme-linked immunosorbent assay showed that GABA was effective in reducing the levels of nitric oxide and nitric oxide synthase in rats treated with DEHP.

Conclusion: DEHP exposure induced anxiety in rats, which may be achieved through elevating nitric oxide and nitric oxide synthase levels in prefrontal cortex of rats. However, the effects caused by DEHP could be alleviated by GABA.

KEYWORDS:

• Gama-aminobutyric acid
• di(2-ethylhexyl) phthalate
• anxiety
• nitric oxide
• nitric oxide synthase

Acknowledgments

We thank the support by Key Laboratory of Food Quality and Safety of Guangdong Province, South China Agricultural University. All data generated or analyzed during this study are included in this manuscript.

Authors’ contributions

Conceived project, designed: HCL. Performed experiments: YTG, HL, TWY, ZCF, MHH, and SQL. Wrote manuscript: Y. Guo and H. Liu. Both authors read and approved the final manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by Natural Science Foundation of Guangdong Province [grant number 2016A030313395] and Special Program for Risk Assessment of Agri-products Quality and Safety of Ministry of Agriculture [grant number GJFP201501202].