Tert-butylhydroquinone preserve testicular steroidogenesis and spermatogenesis in cisplatin-intoxicated rats by targeting oxidative stress, inflammation and apoptosis

• Published in: Toxicology (Amsterdam) 2020-08, Vol.441, p.152528-152528, Article 152528
• Main Authors: Nna, Victor Udo, Ujah, Godwin Adakole, Suleiman, Joseph Bagi, Mohamed, Mahaneem, Nwokocha, Chukwuemeka, Akpan, Timothy Joe, Ekuma, Hope Chinaza, Fubara, Victoria Victor, Kekung-Asu, Catherine Barong, Osim, Eme Efiom
• Format: Article
• Language: English
• Subjects: Apoptosis; Cisplatin; Inflammation; Oxidative stress; Steroidogenesis; Tert-butylhydroquinone
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2020.152528

[Display omitted] •tBHQ upregulates testicular steroidogenesis in cisplatin-intoxicated rats.•tBHQ improves spermatogenesis in cisplatin-intoxicated rats.•tBHQ upregulates Nrf2 and decreases cisplatin-induced oxidative stress in the testis.•tBHQ downregulates cisplatin-induced NF-κB mediated inflammation in the testis.•tBHQ suppresses cisplatin-induced mitochondria-mediated apoptosis in the testis. Cisplatin (Cis) is an effective chemotherapeutic intervention against many cancer types. However, the oxidative stress-related toxicities associated with cancer cell resistance-induced dose scaling has limited its long-term use. In the present study, we explored the benefits of the antioxidant, tert-butylhydroquinone (tBHQ; 50 mg/kg b.w./day, for 14 days) against Cis single dose injection (7 mg/kg b.w., i.p on Day 8), on testicular toxicity of male Wistar rats. Cis triggered testicular and epididymal oxidative stress, testicular inflammation (upregulated NF-κB, TNF-α and IL-1β mRNA levels, and downregulated IL-10 mRNA level), increased testicular apoptosis (increased Bax/Bcl2 and caspase-3 mRNA levels) and decreased testicular germ cells proliferation. Further, Cis decreased testicular steroidogenesis (decreased expression of StAR, CYP11A1, 3β-HSD and 17β-HSD mRNA and proteins) and decreased follicle stimulating hormone, luteinizing hormone and testosterone levels. Cis also decreased sperm count, motility, viability, normal morphology and Johnsen score. However, intervention with tBHQ significantly decreased oxidative stress by upregulating Nrf2 gene, suppressed inflammation, apoptosis and increased testicular germ cells proliferation. tBHQ also increased steroidogenesis and improved sperm parameters. Taken together, tBHQ improves steroidogenesis and spermatogenesis in Cis-intoxicated rats by improving antioxidant status, dampening inflammation and apoptosis, thus improving the proliferative capacity of spermatogenic cells.