In this study the possible protective effect of naringin (NRG) on methotrexate (MTX)–induced damage on testes of rats was investigated. A total of 35 male rats were used as materials.

Animals were divided into 5 groups, 7 rats in each; Group 1 (Control): A single dose injection of physiological saline was administered intraperitoneally on the first day. Group 2 (NRG 100): NRG (100 mg/kg b.w./ day) was given orally for 7 days. Group 3 (MTX): Single dose of 20 mg/kg of MTX was given intraperitoneally on the first day. Group 4 (NRG 50+MTX) 50 mg/kg/day NRG was given for 7 days after a single intraperitoneal injection of 20 mg/kg MTX. Group 5 (NRG 100+MTX): 100 mg/kg/day NRG was given for 7 days after a single intraperitoneal injection of 20 mg/kg MTX.

As a results, MTX increased to malondialdehyde (MDA) levels and decreased glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities when compared to control group. On the other hand, NRG (100 mg/kg) treatment caused decreasing the MDA levels and increa the GSH levels and SOD, CAT, and GSH-Px activities when compared to MTX alone group. NRG 50 mg/kg treatment did not increase SOD activity.

Also, MTX treatment increased caspase-3 and B-cell lymphoma 3 protein (BCL-3) expression levels in testicular tissue when compared to control group. However, NRG (both at the dose of 50 mg/kg and 100 mg/kg) treatment lightened significantly the testis caspase-3 and BCL-3 expression levels when compared to MTX alone group.

In conclusion, NRG (especially at the dose of 100 mg/kg) treatment decreased MTX-induced testicular toxicity in male rats.