Quercetin Mitigates Sulfasalazine-Induced Toxicity by Inhibiting p53-Dependent Apoptosis and DNA Damage in Rat Epididymis, Semen and Bone Marrow

Sulfasalazine, an anti-inflammatory drug used in the treatment of inflammatory bowel disorders poses a threat to male reproductive potential. With a growing interest in the therapeutic ability of dietary flavonoids to mitigate drug-related reproductive dysfunction in males, we evaluated the possible protective potentials of quercetin against sulfasalazine-induced genotoxicity in the bone marrow and apoptosis in testis, semen, and epididymis of Wistar rats. Twenty rats were placed into four groups (n = 5) and orally administered the following for 14 consecutive days: Group 1: 0.5% sodium carboxymethyl cellulose (1 ml/kg). Group 2: quercetin (20 mg/kg). Group 3: sulfasalazine (600 mg/kg). Group 4: sulfasalazine (600 mg/kg) + quercetin (20 mg/kg). Tumor suppressor protein (Tp53), caspase 9, and caspase 3 levels were increased in semen, while TUNEL positive sperm increased in epididymis of sulfasalazine-treated rats, indicative of apoptotic death of sperm. These were significantly decreased in sulfasalazine-treated rats co-administered with quercetin. However, levels of Tp53, caspase 9 and 3 remained unchanged, while TUNEL-stained sperm cells were not evident in testes of rats treated with sulfasalazine. Again, sulfasalazine increased the frequency of micronuclei (MN) in bone marrow of treated rats, evident of its genotoxic potential. MN frequency was, however, decreased in their bone marrow on co-administration of quercetin. In conclusion, our findings suggest that quercetin holds promise in ameliorating the apoptotic death of sperm cells associated with sulfasalazine's detrimental effect on male fertility and DNA.