Investigation of protective effects of rutin\cyclodextrin inclusion complex against testicular damage caused by diisononyl phthalate in rats

Articles in Press

Document Type : Original Article

Authors

1 Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

2 Department of Medical Laboratory Techniques, Vocational School of Health Services, Atatürk University, Erzurum, Turkey

3 Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

4 Department of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey

5 Department of Laboratory and Veterinary Health, Horasan Vocational School, Atatürk University, Erzurum, Turkey

6 Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey

7 Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey

10.22038/ijbms.2025.87549.18910

Abstract

Objective(s): The aim of this study was to investigate the protective effects of Rutin\cyclodextrin (RUT\CD) complex in rats exposed to diisononyl phthalate (DINP).
Materials and Methods: In the study, 35 male Sprague Dawley rats were used. The rats were randomly divided into five groups: Control, DINP, RUT\CD, DINP+RUT\CD100, and DINP+RUT\CD200. The control group received Tween 80 by oral gavage, while the DINP groups received DINP at a dose of 200 mg/kg/bw. RUT+CD groups received the RUT\CD complex by oral gavage. After 14 days of administration, rats were sacrificed, and testicular tissues were used for histopathological and biochemical analyses, and epididymal tissues were used for semen analysis. 
Results: DINP administration caused an increase in MDA level and a decrease in SOD, CAT, GPx1 enzyme activities, and GSH level in rats. RUT\CD administration decreased oxidative stress and increased antioxidant activity. In addition, DINP administration caused a decrease in Nrf-2 and HO-1 levels. DINP caused a significant increase in eIF2α, ATF4, NF-κB, TNF-α, IL-1β, IL-6, Inos, and Cox2 levels in the testicular tissue of rats. RUT\CD administration decreased these levels in a dose-dependent manner. Apoptosis markers p53, Apaf-1, Bax, Bcl-2, and Caspase-3 mRNA transcript levels and Bax and Bcl-2 protein levels were significantly increased in the DINP-administered group. In the DINP+ RUT/CD group, these levels decreased in a dose-dependent manner. Moreover, DINP administration caused an increase in sperm DNA damage.
Conclusion: DINP administration induced testicular toxicity by increasing oxidative stress, apoptosis, and inflammation, and changes in testicular histology. Moreover, RUT\CD administration attenuated DINP-induced toxic effects.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 22 July 2025

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