Marouani Neila, Hallegue Dorsaf, Sakly Mohsen, Benkhalifa Moncef, Ben Rhouma Khémais, Tebourbi Olfa
Laboratory of Integrated Physiology, Faculty of Sciences, Carthage University Tunisia, Bizerte, Jarzouna, Tunisia.
Reproductive Medicine and Medical Cytogenetics Department, Regional University Hospital and School of Medicine, Picardie University Jules Verne, Amiens, France.
Reprod Biol Endocrinol. 2017 May 26;15(1):40. doi: 10.1186/s12958-017-0259-0.
The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis.
Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels. Antioxidant enzymes activities was assessed by determination of superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (HO) production. In addition, glutathione-dependent enzymes and reducing power in testis was evaluated by glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione S-transferase (GST) activities and reduced and oxidized glutathione (GSH - GSSG) levels. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis and the apoptotic index was assessed through the TUNEL assay.
After 10 days of treatment, an increase in LPO level and HO production occurred, while MTs level, SOD and CAT activities were decreased. Also, the Gpx, GR, GST, and GSH activities were decreased, whereas GSSG activity was increased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of DDT-exposed rats. In addition, the apoptotic index was significantly increased in testis of DDT-treated rats.
These results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.
1,1,1-三氯-2,2-双（4-氯苯基）乙烷（p,p'-滴滴涕）是一种已知的持久性有机污染物和雄性生殖毒物。本研究旨在验证氧化应激介导p,p'-滴滴涕诱导睾丸细胞凋亡这一假说。
雄性Wistar大鼠连续10天腹腔注射剂量为50和100mg/kg的该农药。通过生物标志物如脂质过氧化（LPO）和金属硫蛋白（MTs）水平评估氧化应激。通过测定超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和过氧化氢（HO）生成量评估抗氧化酶活性。此外，通过谷胱甘肽过氧化物酶（Gpx）、谷胱甘肽还原酶（GR）、谷胱甘肽S-转移酶（GST）活性以及还原型和氧化型谷胱甘肽（GSH - GSSG）水平评估睾丸中的谷胱甘肽依赖性酶和还原能力。通过琼脂糖凝胶电泳检测DNA片段化评估细胞凋亡。通过TUNEL检测评估生殖细胞凋亡和凋亡指数。
治疗10天后，LPO水平和HO生成量增加，而MTs水平、SOD和CAT活性降低。此外，Gpx、GR、GST和GSH活性降低，而GSSG活性增加。处理组大鼠的睾丸组织显示DNA明显降解为寡核苷酸，如典型的电泳DNA梯状图谱所示。在接触滴滴涕的大鼠生殖细胞中观察到强烈的细胞凋亡。此外，滴滴涕处理组大鼠睾丸的凋亡指数显著增加。
这些结果清楚地表明，滴滴涕亚急性处理会导致大鼠睾丸氧化应激，进而导致细胞凋亡。
