Rats' testicular toxicity induced by bisphenol A is lessened by crocin via an antiapoptotic mechanism and bumped P-glycoprotein expression

Toxicon. 2024 Apr:241:107674. doi: 10.1016/j.toxicon.2024.107674. Epub 2024 Mar 6.

Abstract

Bisphenol A (BPA) engenders testicular toxicity via hydroxyl free radical genesis in rat striatum and depletion of the endogenous antioxidants in the epididymal sperms. The multi-drug resistance efflux carrier; P-glycoprotein (P-gp) expel the BPA from the testis and is responsible for the testicular protection through the deactivation of numerous xenobiotics. In our study, we investigated whether the BPA-induced testicular toxicity could be circumvented through administration of an antioxidant; crocin (Cr). Implication of P-gp expression was also investigated. Rats administered BPA (10 mg/kg b.w. orally for 14 days), dropped the body weight, testes/body weight ratio, total protein content, testosterone, follicle stimulating hormone, luteinizing hormone, and sperm motility & count, total antioxidant status, glutathione content and antioxidant enzymes (superoxide dismutase and catalase), concomitant with the elevation of the percentage abnormal sperm morphology, as well as testicular lipid peroxides and nitrite/nitrate levels. Histopathological examination showed spermatogenesis disorders after the BPA rats exposure. The immunohistochemical study showed up-regulation of the P-gp as evident by increasing immunoreactivity in interstitial cells, with positive localization in some spermatogonia cells. The BPA-treated rats showed positive immunoreactivity against caspase-3. The co-intake of Cr (200 mg/kg b.w./day, i.p. 14 days) along with the BPA, significantly ameliorated all the mentioned parameters, boosted histopathological image, fell the caspase-3 up-regulation, and perched the P-gp expression. We showed that, Cr promotes P-gp as an approach to nurture the testicles against the BPA toxicity. In conclusion; Cr lessens the oxidative stress conditions to safeguard rats from the BPA-induced testicular toxicity and sex hormones abnormalities, reducing apoptosis and up-regulating P-gp.

Keywords: Bisphenol A; Caspase-3; Crocin; P-glycoprotein; Rats; Testes.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Antioxidants* / pharmacology
  • Benzhydryl Compounds* / toxicity
  • Body Weight
  • Carotenoids* / pharmacology
  • Caspase 3 / metabolism
  • Male
  • Oxidative Stress
  • Phenols* / toxicity
  • Rats
  • Semen / metabolism
  • Sperm Motility
  • Testis* / drug effects
  • Testis* / metabolism

Substances

  • Antioxidants
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Benzhydryl Compounds
  • bisphenol A
  • Carotenoids
  • Caspase 3
  • crocin
  • Phenols