Inhibitory effect of Idelalisib on selenite-induced cataract in Sprague Dawley rat pups

ABSTRACT

Purpose

The aim of this study was to evaluate the therapeutic effect of Idelalisib, Apelisib and Copanlisib on 8-day-old cataract SD rat pups.

Materials and methods

The rat model induced by sodium selenate (Na₂SeO₃) was used in this study. Experimental animals were randomly divided into five groups with eight animals in each group. They were control group, Na₂SeO₃ group, Idelalisib group, Apelisib group and Copanlisib group. On days 3, 5 and 7, all rats in Na₂SeO₃, Idelalisib, Apelisib and Copanlisib groups were given subcutaneous injection into the nape with Na₂SeO₃ and control group was given the same amount of saline. For days 1-14, Idelalisib, Apelisib and Copanlisib were given by intragastric administration, respectively, and the same amount of saline was given to the control group and Na₂SeO₃ group. On the 15th day of the experiment, we selected the Idelalisib group with the best effect from all groups, separated their lenses, and further analyzed the crystal proteins, oxidative damage and apoptosis indexes.

Results

The survival rate of rats in control and Idelalisib groups was 100%, the Na₂SeO₃ group was 37.5%, the Apelisib group was 25%, and the Copanlisib group was 0. According to the rat survival rate and lens score, we selected Idelalisib for further analysis of the crystallin, oxidative damage and apoptosis indexes. The results suggested that Na₂SeO₃ leads to cataract formation and crystallin precipitation. The levels of antioxidant enzymes GSH and SOD were decreased in the Na₂SeO₃ group, Nrf-2 and HO-1 were downregulated, Keap1 upregulated, and cleaved caspase-3 and Bax/Bcl-2 upregulated. Idelalisib significantly improved crystallin insolubility, reduced oxidative damage, and inhibited lens apoptosis.

Conclusion

In summary, Idelalisib can significantly improve the progression of Na₂SeO₃-induced cataract in rats. In the future, it may be a potential effective drug candidate for the clinical treatment of cataract.

KEYWORDS:

• Cataract
• Idelalisib
• Sodium selenate

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Additional information

Funding

This work was financially supported by the China Postdoctoral Science Foundation [Grant bs6619026], National Key Research and Development Program of China [Grant 2018YFA0507203], and National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program”, China [Grant 2019ZX09201001].