Aberrations of miR-126-3p, miR-181a and sirtuin1 network mediate Di-(2-ethylhexyl) phthalate-induced testicular damage in rats: The protective role of hesperidin. (30th March 2020)

• Record Type: Journal Article
• Authors: Helmy, Hebatullah S.; Senousy, Mahmoud A.; El-Sahar, Ayman E.; Sayed, Rabab H.; Saad, Muhammed A.; Elbaz, Eman M.
• Is Part Of: Toxicology. Volume 433/434(2020)
• Publication Date: 2020-03-30
• Subjects: Di-(2-ethylhexyl) phthalate -- Hesperidin -- MicroRNA-126-3p -- MicroRNA-181a -- Sirtuin 1; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2020.152406
• Languages: English
• ISSNs: 0300-483X

Abstract

Graphical abstract: Highlights: Administration of DEHP induced testicular damage and toxicity in rats. DEHP disturbed spermatogenesis and testicular redox state. DEHP induced aberrations of miR-126, miR-181a and SIRT1 Network in testis. Hesperidin modulated testicular redox state and aberrations induced by DEHP. Abstract: Recently, oxidative stress was implicated in the environmental contaminant Di-(2-ethylhexyl) phthalate (DEHP)-induced testicular toxicity, however the mechanism is unclear. We investigated the role of oxidative stress-responsive microRNAs in DEHP-induced aberrations and the protective effect of the citrus flavonoid, hesperidin (HSP). Male Wistar rats were randomly allocated into four groups as vehicle-treated control, DEHP-alone group (500 mg/kg/day) for 30 days, and HSP (25 or 50 mg/kg) for 60 days; testicular damage was triggered by oral administration of DEHP (500 mg/kg/day) after thirty days of oral administration of HSP (25 or 50 mg/kg). DEHP administration reduced testis weight coefficient, serum testosterone, testicular 3β-hydroxysteroid dehydrogenase and antioxidant enzyme activities, and elevated serum fatty acid-binding protein-9, testicular malondialdehyde, and Bax/Bcl2 ratio. Aberrant testicular miR-126-3p and miR-181a expression was observed, along with decreased expression of sirtuin1 (SIRT1) and its targets; nuclear factor-erythroid 2-related factor2, haeme oxygenase-1, and superoxide dismutase2. HSP administration significantly ameliorated these changes and restored testicular function in a dose-dependent manner. We highlight a novel role of oxidative stress-miR-126/miR-181a-SIRT1 network in mediating DEHP-induced changes which were reversed by the antioxidant HSP.