Lutein abates doxorubicin-induced testicular toxicity via modulation of Beclin-1/mTOR signaling pathway mediating inhibition of apoptosis, inflammation and oxidonitrergic stress

Abstract

Background
Doxorubicin (DOX) is a medication utilized in several solid tumor treatment. However, using it raises the possibility of serious dose-dependent injury to non-target organs such as the testis. Meanwhile, research has shown that the naturally occurring carotenoid lutein, has androgenic, anti-inflammatory and antioxidant properties. It is unclear, though, if lutein can lessen the damage that doxorubicin causes on the testicles. Therefore, the purpose of this study was to determine how lutein ameliorated doxorubicin-induced testicular toxicity in male Wistar rats.

Methods
Animals were randomly assigned to four groups and treated with 10 ml, of saline, 15 mg/kg of doxorubicin, 40 mg/kg of lutein and DOX with lutein, respectively. Treatment waas done intraperitoneally for 28 days. Hormonal assay, androgenic enzyme quantification accompanied with antioxidant, apoptotic players, pro-inflammatory cytokine and autophagy mediator assays were done using UV/VIS spectrophotometry, ELISA and histological techniques.

Results
The results showed that doxorubicin caused a dysfunctional pituitary-testicular hormonal axis accompanied with low sperm count and semen quality. Also, oxidative stress leading to activation of autophagy which was accompanied with inflammation, apoptosis and fibrosis were all associated with doxorubicin-induced testicular toxicity. However, treatment with lutein significantly abated these changes and restored normal testicular functions.

Conclusion
Lutein abated doxorubicin-induced testicular toxicity via modulation of Beclin-1/mTOR signaling pathway mediating inhibition of apoptosis, inflammation and oxidonitrergic stress.