Vitamin C and Resveratrol Supplementation to Rat Dams Treated with Di(2-ethylhexyl)phthalate: Impact on Reproductive and Oxidative Stress End Points in Male Offspring

Abstract

This study was carried out to assess the influence of di(2-ethylhexyl)phthalate (DEHP) alone or associated with antioxidants on the male reproductive system in newborn rats, emphasizing the implications of oxidative stress and hormonal balance during prenatal and early postnatal periods. Wistar females were exposed by oral route to DEHP alone or associated with antioxidants from gestational day 7 to lactational day 2 according to the following treatment regimens: (C) vehicle control (canola oil + 1% Tween-80); (V) vitamin C (200 mg/kg) + canola oil; (R) resveratrol (10 mg/kg) + canola oil; (D) DEHP (500 mg/kg) + 1% Tween-80; (DV) DEHP (500 mg/kg) + vitamin C (200 mg/kg); and (DR) DEHP (500 mg/kg) + resveratrol (10 mg/kg). Two male pups per litter were randomly selected and necropsied on postnatal day 2. The brain and liver were removed and weighed and anogenital distance (AGD) was measured. Additionally, the testes were removed for assessment of intratesticular testosterone levels and histopathology; the liver was used to measure biomarkers of oxidative stress. Vitamin C and resveratrol alone did not affect the reproductive end points and did not induce oxidative stress. Exposure of dams to DEHP alone and associated with antioxidants resulted in hepatomegaly in offspring and significantly increased the incidence of multinucleated gonocytes in seminiferous cords. Testosterone and AGD presented a trend to decrease in DEHP-exposed groups. Catalase activity increased only in groups exposed to DEHP associated with antioxidants, although GST (gluthatione-S-transferase) activity decreased in all DEHP-exposed groups. The levels of hydroperoxides increased only in group exposed to DEHP associated with vitamin C. These results indicate that the association of DEHP with antioxidants was unable to ameliorate DEHP-induced reproductive changes, and the coadministration of DEHP and these antioxidants might even contribute to an overall increase in oxidative stress.

Toona sinensisLeaf Aqueous Extract Improves the Functions of Sperm and Testes via Regulating Testicular Proteins in Rats under Oxidative Stress

“…The increased ROS level has been reported to be associated with the decreasing HMG-CoA synthase expression resulting in the decline of steroidogenesis and testosterone concentration [24]. The activities of enzymes in steroidogenesis were found to be recovered by vitamin C in testes [25]. The HMG-CoA synthase protein expression which increased significantly by TSL-A in this study may contribute to the maintenance of steroidogenesis.…”

The effects of di(2‐ethylhexyl)phthalate on rat liver in relation to selenium status

“…However, resveratrol and vitamin C did not provide any protection against the hepatoxicity of DEHP in rats (Botelho et al . ).…”

Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

“…For instance, epidemiologic studies have reported links between urinary phthalates (e.g., mono-isobutyl phthalate (MiBP)) and phthalate metabolites (e.g., di-2-ethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP)) with increased levels of lipid peroxidation, inflammation and decreased levels of antioxidants [32–34]. Prenatal phthalate exposure was also associated with increased oxidative stress in male rat offspring [35], providing some evidence of fetal programming by phthalate exposure. Limited data, however, are available on the effects of phthalates on isoprostane levels during pregnancy, a particularly sensitive period for phthalate exposure.…”