Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Oxid Med Cell Longev. 2009 Apr-Jun;2(2):73-81. doi: 10.4161/oxim.2.2.8177.
The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2(nd) group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients.
睾丸是一个免疫特惠器官。支持细胞可以形成血睾屏障，保护精子免受自身免疫系统的攻击。严重疾病、细菌感染和慢性炎症性疾病可能会抑制精子发生，但机制尚不清楚。我们的目标是帮助理解这种机制，以开发针对暂时性或永久性睾丸功能障碍的保护剂。脂多糖 (LPS) 被用作动物败血症的模型，而左旋肉碱 (LCR) 则被用作保护剂。总共 60 只雄性瑞士白化大鼠被分为四组（每组 15 只）。对照组给予生理盐水；第 2 组给予 LCR（500mg/kg，腹腔内注射，一次）。第 3 组给予 LPS（5mg/kg，腹腔内注射一次），第 4 组在 3 小时后给予 LCR 加 LPS。每组中 5 只大鼠用于组织病理学检查。其余 10 只大鼠评估生化参数。实验结束时，动物用乙醚轻度麻醉，采集血样，在冰上解剖睾丸。从每个动物的附睾尾评估精子计数和活力。此外，通过测量睾丸中还原型谷胱甘肽 (GSH)、丙二醛 (MDA) 和 8-羟基脱氧鸟苷 (8-HDG，氧化损伤的 DNA 加合物) 的含量来评估氧化应激。睾丸匀浆中还评估了促炎介质一氧化氮 (NO) 以及乳酸脱氢酶 (LDHx)同工酶-x 活性，后者是精子代谢正常的指标。睾丸组织中白细胞介素 (IL)-2 水平也被评估为辅助性 T 细胞功能的标志物。实验结果显示，LPS 诱导精子计数和活力显著降低、生精小管阻塞、少精子症和睾丸切片中扩张充血的血管，同时睾丸 GSH 含量和 LDHx 活性降低。此外，睾丸 MDA、8-HDG（睾丸 DNA 中的）和 NO 以及血清 IL-2 水平升高。LPS 前给予 LCR 可使精子计数和活力恢复正常水平。此外，睾丸 GSH、MDA、8-HDG 和 NO 的含量也恢复到相应的对照值。此外，LCR+LPS 治疗大鼠的血清 IL-2 水平和组织学异常明显改善。总之，LPS 增加了睾丸中的促炎和氧化应激标志物，导致明显的睾丸功能障碍。左旋肉碱通过抗氧化和/或抗炎机制改善这些作用，提示其在严重感染或败血症患者中具有保护男性生育力的作用。
