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.
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.
Botelho
Giuliana G K
GG
Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil. giu_kasecker@uol.com.br
Bufalo
Aedra C
AC
Boareto
Ana Claudia
AC
Muller
Juliane C
JC
Morais
Rosana N
RN
Martino-Andrade
Anderson J
AJ
Lemos
Karen R
KR
Dalsenter
Paulo R
PR
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000473:pathology
D000975:Antioxidants; D004785:Environmental Pollutants; D013267:Stilbenes; D004051:Diethylhexyl Phthalate; D002374:Catalase; D005982:Glutathione Transferase; D001205:Ascorbic Acid; D000077185:Resveratrol