The male reproductive function, particularly the testes, and the related hormones are sensitive to various xenobiotics. This work aimed for the first time to assess Nigella sativa floral honey (NS floral honey) and multi-floral honey (M-floral honey) versus Nigella sativa oil (NS oil) against rat testicular degeneration induced with azathioprine (AZA). A total of 40 male Wister rats were assigned into 5 groups: (1) control, (2) 15 mg/kg of AZA, (3) AZA + 1.4 mL/kg of M-floral honey, (4) AZA + 1.4 mL/kg of NS floral honey, and (5) AZA + 500 mg/kg of NA oil. Total testosterone (TT), free testosterone (FT), free androgen index (FAI), gonadotrophins, sex-hormone-binding globulin (SHBG), apoptosis markers, and redox status were assessed to clarify the possible protective mechanisms. Pituitary-testicular axis disruption, apoptosis markers, poor redox status, and sperm quality (count, viability, and motility) were set with AZA. Serum TT, SHBG, and absolute and relative testis weight were significantly restored in the NS oil and NS floral honey groups. Meanwhile, the NS oil group exhibited a significant elevation in FT and FAI. Serum gonadotrophins increased significantly in the NS floral honey (p < 0.01) and M-floral honey and NS oil (p < 0.05) groups. Testicular caspase-3, caspase-9, and nitric oxide showed significant improvement in the NS floral honey and NS oil groups. NS oil supplementation significantly normalized redox status (p < 0.05), whereas NS floral honey improved malondialdehyde and superoxide dismutase activity. Sperm quality exhibited a significant improvement in the NS oil group (p < 0.05). M-floral honey did not show reliable results. Although NS floral honey could protect against testicular damage, it did not upgrade to the level of improvement achieved with NS oil. We claim that further clinical studies are essential for focusing on the quality and quantity of bioactive constituents.
Keywords: Nigella sativa floral honey; Nigella sativa oil; apoptosis; multi-floral honey; pituitary–testicular axis; redox status; testicular degeneration.