Ameliorative Effect of Policosanol on High-Fat Diet-Induced Testicular Dysfunction: Implications of ROS/SIRT1 and Apoptotic Signaling Pathways in Rats.

High-fat diet (HFD) intake may lead to testicular dysfunction, mostly attributed to hormonal disturbances and spermatozoa deformities. The present study was designed to demonstrate the policosanol (POL) effect on testicular dysfunction due to HFD intake. Rats were randomly divided into three groups; one received HFD for 16 weeks and then treated with POL (10 mg/kg/day) orally for 4 weeks along with HFD intake. The second group received HFD only and served as the HFD control group. The third group was referred to as normal control (NC) and kept on a normal chow diet. Rats subjected to HFD showed marked weight gain, dyslipidemia, insulin resistance, excessive generation of reactive oxygen species (ROS) and inflammation status. Silent information regulator transcript-1 (SIRT1) protein levels and mRNA expression levels of nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) showed significant decrease in the HFD group. Bax and caspase-3, along with Beclin-1, showed substantial increases along with Bcl-2 decrease. POL administration successfully reversed all these abnormalities which may be attributed to activation of SIRT1/Nrf2/HO-1 signaling. Collectively, POL administration may be a promising therapeutic approach against HFD-testicular dysfunction via improving metabolic status, attenuating oxidative stress and inflammation, and modulating apoptosis and autophagy.