Protective Effects of Adenosine Triphosphate and Flunarizine on Erlotinib-Induced Ovarian Damage: An Experimental Study

(1) Background: Erlotinib is a tyrosine kinase inhibitor (TKI) widely used in cancer therapy; however, its potential adverse effects on ovarian tissue have not been fully elucidated. The present study aimed to investigate erlotinib-induced ovarian injury and to evaluate the protective effects of adenosine triphosphate (ATP) and flunarizine, administered alone or in combination, using biochemical and histopathological analyses in a rat model. (2) Methods: Thirty female rats were randomly allocated into five groups (n = 6 per group): healthy control, erlotinib, ATP + erlotinib, flunarizine + erlotinib, and ATP + flunarizine + erlotinib. ATP (5 mg/kg, intraperitoneal) and flunarizine (5 mg/kg, oral gavage) were administered daily for two weeks, while erlotinib (5 mg/kg) was given orally every two days for two weeks. Ovarian tissues were collected for oxidative stress analysis and histopathological evaluation, and blood samples were obtained for the measurement of serum prolactin and AMH levels. (3) Results: Erlotinib administration resulted in significant oxidative stress and histopathological alterations in ovarian tissue, accompanied by a reduction in serum AMH levels, while prolactin levels remained unchanged. Treatment with ATP or flunarizine partially attenuated these alterations. (4) Conclusions: Combined ATP and flunarizine administration showed stronger protective effects, improving biochemical parameters and preserving ovarian histology, suggesting a protective role against erlotinib-induced ovarian injury. © 2026 by the authors.