Therapeutic Role of Auraptene Against Letrozole-Induced Estrogen Disturbance in Female Rats

Abstract

Estrogen insufficiency impedes organs functions and induces cytotoxicity, as estrogen is considered the pivotal regulator for normal development and function of multi-organs. The present study was designed to investigate the effectiveness of Auraptene, the monoterpene coumarin derivative compound with anti-oxidant, anti-inflammatory, multi-protective effects in improvement of estrogen insufficiency-induced cytotoxicity in sensitive organs like liver and cerebellum. Methods: 20 female Wistar albino rats, weighing 110±130g, were randomly categorized into 4 groups including: Group A: control group (0.5 ml of 0.9% NaCl /rat/day), Group B: AUR group (0.15 mg/kg for 2 weeks). Group C: letrozole group (0.04 mg/kg, for 2 weeks), Group D: Letrozole plus AUR group; letrozole (0.04 mg/kg) along with AUR (0.15 mg/kg) for 2 weeks. After 24 hours from the last dose rats were sacrificed by cervical dislocation, their skulls and abdominal cavities were opened, cerebellum and liver were dissected, and histopathological changes were examined. Results: Auraptene treatment evidently amended letrozole-cytotoxicity, letrozole treatment incited hepatic-microstructure alterations including distortion of portal area, sinusoidal dilation along with hepatocellular necrosis and vascular degeneration. Likewise, cerebellar sections revealed cerebral cortex obstruction, Purkinje cells shrinkage with a reduction in their numbers and empty areas in between them, as well as neural vacuolation and cells clumping in granular layer. Conclusion: These findings confirm the potential effects of auraptene in attenuate Letrozole-induced estrogen insufficiency cytotoxicity in female rats.