Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Toxicol In Vitro. 2010 Jun;24(4):1266-72. doi: 10.1016/j.tiv.2010.01.009. Epub 2010 Feb 1.
Inflammatory reactions that result from microbial infections, both localized and systemic, are reported to cause transient or permanent male infertility. The cellular mechanisms underlying the inhibitory effect of microbial infection on spermatogenesis is not fully understood. However, there is evidence that spermatogenesis is affected by bacterial lipopolysaccharides (LPS) that induce acute inflammatory responses. The aim here was to use LPS treatments to investigate the potential oxidative stress and toxicity in primary cultures of adult rat Sertoli cells. The Sertoli cells were established and incubated with different concentrations of LPS (5, 10 or 20 microg/ml) for 6, 12 and 24h. Lipid peroxidation (LPO) and hydrogen peroxide (H(2)O(2)) production, along with superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), reduced glutathione (GSH), lactate, lactic acid dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and beta-glucuronidase were measured in these cells. LPO as well as H(2)O(2) production were significantly increased while antioxidant enzyme activities and GSH concentration were significantly depressed. Effects were dose and time-dependent at all incubation periods with 10 and 20 microg/ml LPS. Moreover, markers of Sertoli cell function such as lactate production, LDH, gamma-GT and beta-glucuronidase activities were decreased in a time and dose-dependent manner. Incubation of Sertoli cells with 5 microg/ml LPS for 12 and 24h significantly increased oxidative status but significantly decreased the antioxidant enzyme activities, GSH concentration and Sertoli cell markers. In contrast, the oxidative and antioxidant status and markers of Sertoli cell function did not show any significant change in treated Sertoli cells with 5 microg/ml LPS for 6h. Therefore, it may be concluded that LPS induces oxidative stress in Sertoli cells and adversely affects Sertoli cell functions.
微生物感染引起的炎症反应，无论是局部的还是全身的，据报道会导致暂时性或永久性的男性不育。微生物感染对精子发生的抑制作用的细胞机制尚未完全了解。然而，有证据表明，细菌脂多糖（LPS）诱导急性炎症反应会影响精子发生。本研究旨在使用 LPS 处理来研究成年大鼠支持细胞原代培养物中的潜在氧化应激和毒性。建立了支持细胞并与不同浓度的 LPS（5、10 或 20μg/ml）孵育 6、12 和 24h。测量了这些细胞中的脂质过氧化（LPO）和过氧化氢（H₂O₂）的产生，以及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽-S-转移酶（GST）、谷胱甘肽还原酶（GR）、还原型谷胱甘肽（GSH）、乳酸、乳酸脱氢酶（LDH）、γ-谷氨酰转肽酶（γ-GT）和β-葡萄糖醛酸酶。LPO 以及 H₂O₂ 的产生显著增加，而抗氧化酶活性和 GSH 浓度则显著降低。在所有孵育期内，用 10 和 20μg/ml LPS 处理时，这些影响均呈剂量和时间依赖性。此外，乳酸的产生、LDH、γ-GT 和β-葡萄糖醛酸酶的活性等支持细胞功能的标志物也呈时间和剂量依赖性下降。用 5μg/ml LPS 孵育支持细胞 12 和 24h 可显著增加氧化状态，但显著降低抗氧化酶活性、GSH 浓度和支持细胞标志物。相比之下，用 5μg/ml LPS 孵育支持细胞 6h 时，氧化和抗氧化状态以及支持细胞功能的标志物没有发生任何显著变化。因此，可以得出结论，LPS 诱导支持细胞中的氧化应激，并对支持细胞功能产生不利影响。
