Evaluation of Hesperidin and Taurine for Mitigating Letrozole-induced Uterine Toxicity in Rats: Histopathological, Molecular, and Biochemical Insights

OpenAlex İngilizce

Abstract Objectives Letrozole (LTZ), an aromatase inhibitor, is associated with significant side effects such as uterine toxicity. This study investigated the potential of hesperidin (HSP) and taurine (TAU), both natural antioxidant molecules, to mitigate LTZ-induced uterine toxicity. Methods A total of 48 female rats were divided into six groups and treated orally for 30 days as follows: Control (sham), LTZ (1 mg/kg), HSP (100 mg/kg), TAU (100 mg/kg), LTZ+HSP, and LTZ+TAU. Histopathological, gene expression, and biochemical analyses were conducted on uterine tissues and serum samples. Results LTZ caused a significant decrease in serum IL-1β, IL-6, estradiol, and FSH levels (p<0.05). It reduced SOD, CAT activities, and GSH levels while increasing tissue MDA levels. Additionally, it led to a significant increase in Bax, caspase-3, COX-2, iNOS, and TNF-α gene expression. HSP and TAU did not significantly alter hormone levels (p>0.05). However, HSP significantly reduced oxidative stress (p<0.05), decreased the expression of genes related to apoptosis and inflammation (p<0.05), and significantly lowered serum cytokine levels while increasing the expression of anti-apoptotic genes. Both HSP and TAU mitigated LTZ-induced cystic dilatation and hyperemia in the uterine glands. TAU did not significantly affect IL-1β and IL-6 levels or the expression of apoptosis-related genes (p>0.05). Although TAU exhibited effects similar to HSP in certain parameters, its protective efficacy was comparatively less pronounced. Conclusions The results suggest that HSP is a promising agent for mitigating LTZ-induced uterine toxicity. However, further studies with different doses and application protocols are required to more definitively elucidate the potential effects of TAU.