Alterations of di(n-butyl)phthalate-induced oxidative stress in the testis of hypothyroid rats

Abstract

The aim of the present study was to investigate the effects of di(n-butyl)phthalate (DBP) on oxidative damage in the testes of hypothyroid rats. Hypothyroidism was induced by administering 0.1% 6-N-propyl-2-thiouracil (PTU) in drinking water for 30 days. DBP was dissolved in corn oil and administered daily for 30 days by oral gavage. Significant decreases in testes weight were observed both in normal (DBP) and hypothyroid (PTU + DBP) groups. Serum testosterone concentrations were significantly reduced in the DBP groups, but no significant change occurred in hypothyroid rats. Di(n-butyl)phthalate significantly increased malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced oxidative lipid (MDA) and DNA (8-OHdG) damage were less in hypothyroid rats. PTU-induced hypothyroid rats decreased testicular catalase activity, whereas superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities did not show any significant changes. However, the DBP and PTU + DBP groups significantly increased catalase and SOD activities in testis. The testicular expression of thyroid hormone receptor α-1 (TRα-1) was significantly increased in the DBP and PTU + DBP groups. In contrast, androgen receptor (AR) protein levels were not detected in the DBP and PTU + DBP groups. Di(n-butyl)phthalate significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) and retinoid X receptor-α (RXR-α) levels. Peroxisome proliferators activated-receptors-α and RXR-r protein levels were markedly decreased in the DBP groups, but these protein levels increased in the PTU + DBP group, as compared to DBP alone. These results suggest that PTU-induced hypothyroidism may protect against oxidative damage in the testis, probably due to the regulation of the PPAR and RXR expression, which is associated with decreased metabolic activation of DBP.

Keywords:

• DBP
• thyroid hormone
• catalase
• SOD
• glutathione peroxidase
• TR
• PPAR

Acknowledgments

This work was supported in part by the Korea Research Foundation (KRF-2004-041- E00392) and Endocrine Disruptor Research from the National Institute of Toxicological Research (Seoul, Korea) grants funded by the Korean Government. Ryu J.Y. was supported by grants from the Brain Korea 21 project.