Affiliations 

  • 1 Department of Physiology, College of Medical Sciences, University of Calabar, P.M.B. 1115 Calabar, Cross River State, Nigeria. Electronic address: victorudon@unical.edu.ng
  • 2 Department of Physiology, College of Medical Sciences, University of Calabar, P.M.B. 1115 Calabar, Cross River State, Nigeria
  • 3 Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia; Department of Science Laboratory, Technology, Akanu Ibiam Federal, Polytechnic, Unwana, Nigeria
  • 4 Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia; Unit of Integrative Medicine, Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia
  • 5 Department of Basic Medical Sciences (Physiology Section). The University of the West Indies, Mona, Kingston 7, Jamaica
Toxicology, 2020 08;441:152528.
PMID: 32565124 DOI: 10.1016/j.tox.2020.152528

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.