Modulatory effects of concomitant quercetin/sitagliptin administration on the ovarian histological and biochemical alterations provoked by doxorubicin in a streptozotocin-induced diabetic rat model

ABSTRACT

Limited literature was available on the effects of sitagliptin or quercetin treatments on doxorubicin induced ovarian dysfunction in diabetic animals. The study aim was test the efficacy and suggested mechanisms of quercetin/sitagliptin combined treatment on the doxorubicin-induced ovarian toxicity in rat model with streptozotocin-induced diabetes. Forty eight female Wistar rats were divided into six groups: 1) Control; 2) Streptozotocin induced diabetes; 3) Streptozotocin-induced diabetes + doxorubicin ovarian damage; 4) Streptozotocin-induced diabetes + doxorubicin ovarian damage with; 5) Streptozotocin-induced diabetes + doxorubicin ovarian damage with sitagliptin treatment and 6) Streptozotocin-induced diabetes + doxorubicin ovarian damage with concomitant quercetin/sitagliptin treatment. Biochemical tests for serum estrogen, progesterone, insulin, blood glucose, and ovarian levels of malondialdehyde, nitric oxide, and superoxide dismutase and qRT-PCR for NOBOX, FSHr, and iNOS genes were performed. Histological evaluation was done on ovary sections with hematoxylin and eosin and immunohistochemistry for 8-OHdG and iNOS followed by morphometric analysis. The streptozotocin-induced diabetic group showed varying degrees of follicle atresia and altered biochemical parameters, both were marked in the streptozotocin-induced diabetic + doxorubicin group. The mRNA of NOBOX, FSHr, and iNOS genes were disturbed with increased immunoexpression of iNOS and 8-OHdG. Quercetin and/or sitagliptin administration improved all altered histological and biochemical parameters and was more effective as a combined treatment. The study suggested equal efficacy of both quercetin and sitagliptin in mitigating the doxorubicin-induced ovarian toxicity in the streptozotocin diabetic rat model, and the combined therapy showed anti-inflammatory, anti-antioxidant, and anti-DNA damage mechanisms.

KEYWORDS:

• Doxorubicin
• sitagliptin
• quercetin
• streptozotocin-induced diabetes
• immunohistochemistry
• follicular atresia
• inflammation

Acknowledgment

The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code: 22UQU4331391DSR04.

Data availability statement

All generated or analyzed data in the current study were included in the published version of the article and any query will be upon request to the corresponding author.

Disclosure statement

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

Author contributions

Ahmed Morsi interpreted and wrote initial draft, figure legends, text descriptions of histological observations, and participated in the discussion. Eman Faruk participated in writing the paper, data search, preparing histological sections, and photomicrography. Engy Medhat carried out biochemical and gene studies, analysis, interpretation, and participated in manuscript writing. Neama Taha participated in the analysis of biochemical results, correlated research findings, and wrote the final draft of the paper. Usama Fouad collected literature data, performed morphometric study, analysis, and results correlation. All authors approved the final version of the manuscript.

Additional information

Funding

This research did not receive any financial support from funding agencies in the public, commercial, or not-for-profit sectors.