Doxorubicin-mediated testicular toxicity is associated with dysregulated mTOR/Beclin-1 pathways, oxidative stress, inflammation and apoptosis in Wistar rats: preventive role of lutein.

Abstract

Background: Lutein offers undoubted hope for preventing doxorubicin uncharacteristic reproductive function which remains a worldwide health concern in cancer chemotherapy. However, the mechanisms underlying the effect of lutein on maintaining the male reproductive milieu have not yet been fully identified. The current study investigates the preventive effect of lutein in doxorubicin-induced testicular toxicity.

Methods: Twenty male Wistar rats were randomly assigned into four groups of five animals (n = 5) and were pretreated with lutein (40 mg/kg i.p) prior to doxorubicin treatment (15 mg/kg i.p). Following the end of the experiment, animals were euthanized and the testes were collected and processed for semen and biochemical analysis.

Results: The results revealed that exposure to doxorubicin caused hormonal imbalance, reduced semen quality and elicited oxidative stress, inflammatory reactions, apoptosis as well as dysregulation of autophagic process which was accompanied by fibrosis and histomorphological aberrations. Interestingly, pretreatment with lutein significantly restored hormonal balance and protected against the adverse effects of doxorubicin.

Conclusions: The findings of this study showed that lutein prevents doxorubicin-mediated testicular toxicity via modulation autophagic pathways accompanied with inhibition of oxidative stress, inflammation and apoptosis.