Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p–NF–κB/VCAM-1 signaling. (November 2022)

• Record Type: Journal Article
• Authors: Shafiey, Sara I.; Abo-Saif, Ali A.; Abo-Youssef, Amira M.; Mohamed, Wafaa R.
• Is Part Of: Food and chemical toxicology. Volume 169(2022)
• Publication Date: 2022-11
• Subjects: Rivaroxaban -- Cisplatin -- Testicular damage -- Inflammation -- Coagulation; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.113419
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX (7 mg/kg/day), CP (10 mg/kg), RVX 5 mg + CP and RVX 7 mg + CP. Serum testosterone and testicular ALT, AST, and ALP were assessed. Testicular oxidative stress and antioxidant parameters and inflammatory indicators including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assessed. qRT-PCR was used to determine mRNA expression of 3β-hydroxysteroid dehydrogenase (3β–HSD), 17β-hydroxysteroid dehydrogenase (17β–HSD), and steroidogenic acute regulatory protein (stAR). Protein expressions of p -Nuclear factor kappa B ( p - NF-κB) and vascular cell adhesion protein-1 (VCAM-1) were analyzed by Western blot analysis. Tissue factor (TF) expression was immunohistochemically analyzed. Results revealed that RVX significantly increased serum testosterone and sperm count while significantly reduced IL-1β and TNF-α. It significantly decreased tissue MDA and NO contents while increased SOD and GPx. In addition, RVX attenuated CP-induced histopathological aberrations and normalized TF. It also decreased the VCAM-1 and p –NF–κB expression and showed strong expression of 3β-HSD, 17β-HSD, and stAR, indicating improvement of steroidogenesis. In conclusion, RVX counteracted testicular damage by CP via suppressing oxidative stress, inflammation, and coagulation and downregulating p –NF–κB/VCAM-1 signaling. Graphical abstract: Image 1 Highlights: Cisplatin reduced sperm count and testosterone which was revealed by rivaroxaban. Cisplatin induced oxidative stress, inflammation and histopathological aberrations. Rivaroxaban counteracted oxidative stress and histopathological aberrations. Rivaroxaban reduced VCAM-1, p–NF–κB, IL-1β, and TNF-α expression. Rivaroxaban upregulated 3β-HSD, 17β-HSD, and stAR and normalized TF.