Involvement of Fas/FasL system in apoptotic signaling in testicular germ cells of male Wistar rats injected i.v. with microcystins

Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, People's Republic of China.
Toxicon (Impact Factor: 2.49). 08/2009; 54(1):1-7. DOI: 10.1016/j.toxicon.2009.01.035
Source: PubMed


Previous studies have shown that gonads were the second target organ of microcystins (MCs), and that MCs exposure exerted obvious toxic effects on male reproductive system of mammals. However, relevant molecular evidences are still lacking. Fas-signaling pathway plays a key role in toxicant-induced germ cell apoptosis. This study was to evaluate the responses of Fas/FasL system related genes and proteins in testes of rats injected intravenously with MCs. Enhanced apoptosis of germ cells in the testes of MCs-treated rats was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) associated with up-regulation of the Fas/FasL system. Both Fas and FasL protein expression were induced evidently from 1 h post-injection, and this high expression level maintained throughout the experiment. In addition, the activation of caspase-8 and caspase-3 protein was also observed, which were indicators of apoptosis. These results suggested the likely involvement of Fas/FasL system in the MCs-induced germ cell apoptosis. It is also suggested that MCs can cause damage to Sertoli cells directly.

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Available from: Huiying Li, Oct 08, 2015
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    • "86.7 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h c-fos ↑, c-jun ↑, c-myc ↑ [56] Male Wistar rats Cyanobacterial crude extracts i.v. 80.5 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h Apoptosis, induction of Fas/FasL system [57] Male Wistar rats Cyanobacterial crude extracts i.v. 87 g MC-LR eq/kg 1, 2, 4, 6, 12, 24 h p53 ↑, Bax ↑, Bcl-2 "
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    • "It is well known that MCs are harmful or toxic to both aquatic animals and mammals including humans (Malbrouck and Kestemont, 2006; Li et al., 2005, 2013). So far, there have been identified around 90 molecular variants of MCs (Pearson et al., 2010) and microcystin-LR (MC-LR) is the most common and toxic variant (Xiong et al., 2009). Because of its high health risks, it is very necessary to evaluate toxic effects of MCs and build a possible dose–effect and/or time-effect relationships. "
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    ABSTRACT: Microcystin-LR (MC-LR) is the most toxic and common among microcystins. In order to understand the possible molecular mechanisms of hepatic antioxidation and detoxification, the activities and transcriptional levels of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferases (GST), and glutathione (GSH) contents as well as histopathological changes were studied in the liver of female zebrafish injected intraperitoneally (i.p.) at doses of 50 and 200μg MC-LR kg(-1) body weight (BW) respectively. In the low dose group (50μg MC-LR kg(-1)), zebrafish displayed a little unease at the initial 1h post-injection (hpi), slight hepatic injury and quick recovery, and enhanced enzymatic activities and up-regulated gene expression of antioxidant enzymes. In contrast, high dose of MC-LR (200μg MC-LR kg(-1)) resulted in uneasiness and frantic swimming, severe hepatic injury, and suppressed enzymatic activities and down-regulated gene expression of antioxidant enzymes. GSH depletion in both dose groups may be explained by enhanced antioxidant reactions and higher rates of MC conjugation, suggesting the crucial roles of GSH in both cellular antioxidant protection and MC-LR detoxification. This study demonstrated that administration of MC-LR caused a positive response in the low dose group but a negative response in the high dose group. Hepatic positive/negative responses in the low/high dose group might result from an increased/decreased synthesis of antioxidant enzymes at the molecular level, respectively. These results illustrated that antioxidant status played an important role in zebrafish protection against MC-LR-caused oxidative stress through regulating antioxidant enzyme gene expression and activities. Copyright © 2014 Elsevier Ltd. All rights reserved.
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    • "A single dose i.v. in rats resulted in an increase in liver sphingolipid, implicating ceramide-mediated apoptosis, a dosedependent decrease in PP2A expression, and a dose-dependent decreased expression of Bcl2 family proteins, involved in cell cycle/apoptosis regulation (Billam et al., 2008). Toxic effect may ultimately depend upon the ability of antioxidant pathways to counteract oxidative damage (Jayaraj et al., 2006, 2007; Xiong et al., 2009). Furthermore, as tumor-promoting compounds, MCs, through dysregulation of phosphorylation, may result in promotion of proto-oncogenes, while MCs also induce DNA damage in hepatocytes along with other cell lines (Zegura et al., 2003, 2008). "
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    ABSTRACT: In freshwater, harmful cyanobacterial blooms threaten to increase with global climate change and eutrophication of surface waters. In addition to the burden and necessity of removal of algal material during water treatment processes, bloom-forming cyanobacteria can produce a class of remarkably stable toxins, microcystins, difficult to remove from drinking water sources. A number of animal intoxications over the past 20 years have served as sentinels for widespread risk presented by microcystins. Cyanobacterial blooms have the potential to threaten severely both public health and the regional economy of affected communities, particularly those with limited infrastructure or resources. Our main objectives were to assess whether existing water treatment infrastructure provides sufficient protection against microcystin exposure, identify available options feasible to implement in resource-limited communities in bloom scenarios and to identify strategies for improved solutions. Finally, interventions at the watershed level aimed at bloom prevention and risk reduction for entry into potable water sources were outlined. We evaluated primary studies, reviews and reports for treatment options for microcystins in surface waters, potable water sources and treatment plants. Because of the difficulty of removal of microcystins, prevention is ideal; once in the public water supply, the coarse removal of cyanobacterial cells combined with secondary carbon filtration of dissolved toxins currently provides the greatest potential for protection of public health. Options for point of use filtration must be optimized to provide affordable and adequate protection for affected communities. Copyright © 2013 John Wiley & Sons, Ltd.
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