Erthal Rafaela P, Siervo Gláucia E M L, Silveira Lívia T R, Scarano Wellerson R, Fernandes Glaura S A
Department of General Biology, Biological Sciences Center, State University of Londrina, Rodovia Celso Garcia Cid, PR 445 - Km 380, Campus Universitário, 86057-970, Londrina, Paraná, Brazil.
Department of Morphology, Institute of Biosciences, State University Paulista, Botucatu, Rua Prof. Dr. Antonio Celso Wagner Zanin, Rubião Júnior, 18618-970, Botucatu, São Paulo, Brazil.
Reprod Fertil Dev. 2018 Mar;30(3):442-450. doi: 10.1071/RD17180.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered one of the most toxic dioxins. The effects of TCDD are exerted via binding to the aryl hydrocarbon receptor (AhR). The aim of the present study was to evaluate the possible protective effects of resveratrol, an AhR antagonist, against testicular damage caused by TCDD exposure during pregnancy. Pregnant female Sprague-Dawley rats were divided into four groups: a control group; a group treated with 1µgkg-1, p.o., TCDD on Gestational Day (GD) 15; a group treated with 20µgkg-1, p.o., resveratrol on GD10-21; and a group treated with both TCDD and resveratrol. Rats were weighed and killed, and neonatal testes were collected for histopathological analysis on Postnatal Day (PND) 1. At PND90, adult male rats were killed and the testes collected for histopathological analysis and determination of sperm count. Resveratrol had a protective effect against the effects of TCDD on Sertoli cell number in adult and neonate testes, as well as against the effects of TCDD on abnormal seminiferous tubules in adults. Combined administration of TCDD and resveratrol altered the kinetics of spermatogenesis and the proportion of neonatal testicular compartments compared with the control group In addition, combined TCDD and resveratrol treatment decreased seminiferous tubule diameter in adult male rats compared with the control group. In conclusion, resveratrol may protect against some TCDD-induced testicular damage, but, based on the parameters assessed, the administration of resveratrol and TCDD in combination may result in more severe toxicity than administration of either drug alone.
2,3,7,8-四氯二苯并对二恶英(TCDD)被认为是毒性最强的二恶英之一。TCDD的作用是通过与芳烃受体(AhR)结合来发挥的。本研究的目的是评估AhR拮抗剂白藜芦醇对孕期暴露于TCDD所致睾丸损伤的潜在保护作用。将怀孕的雌性Sprague-Dawley大鼠分为四组:对照组;在妊娠第15天经口给予1µg/kg TCDD的组;在妊娠第10 - 21天经口给予20µg/kg白藜芦醇的组;以及同时给予TCDD和白藜芦醇的组。对大鼠进行称重并处死,在出生后第1天收集新生睾丸进行组织病理学分析。在出生后第90天,处死成年雄性大鼠,收集睾丸进行组织病理学分析并测定精子数量。白藜芦醇对TCDD对成年和新生睾丸支持细胞数量的影响以及对TCDD对成年大鼠生精小管异常的影响具有保护作用。与对照组相比,TCDD和白藜芦醇联合给药改变了精子发生的动力学以及新生睾丸各部分的比例。此外,与对照组相比,TCDD和白藜芦醇联合处理降低了成年雄性大鼠生精小管的直径。总之,白藜芦醇可能对某些TCDD诱导的睾丸损伤具有保护作用,但根据所评估的参数,白藜芦醇和TCDD联合给药可能比单独使用任何一种药物导致更严重的毒性。