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 qRTPCR for NOBOX, FSHr, and iNOS genes were performed. Histological evaluation was done onovary
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