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

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 eIF2 alpha, ATF4, NF-kappa B, TNF-alpha, IL-1 beta, 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.