Cellular and molecular mechanisms of sulfur mustard toxicity on spermatozoa and male fertility

Harchegani, Asghar Beigi; Niha, Mahdiyeh Mirnam; Sohrabiyan, Milad; Ghatrehsamani, Mahdi; Tahmasbpour, Eisa; Shahriary, Alireza

doi:10.1039/c8tx00062j

Cited by 7 publications

(3 citation statements)

References 70 publications

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“…In this context, the capacity of melatonin to modulate the inflammation-immune axis (48,49) should mitigate the pathological features induced by sulfur mustard through the modulation of the inflammation-immune axis. Some studies have suggested that the enhancement of oxidative species production or weakening of antioxidant mechanisms are crucial in the acute toxicity of sulfur mustard and long-term effects following acute poisoning (22,38,(50)(51)(52)(53). The powerful nitrosating agent peroxynitrite (ONOO • ) is involved in detrimental effects of all mustards as it covalently modifies all the principal types of biomolecules including membrane lipids, thiols, proteins and purine and pyrimidine bases (54)(55)(56).…”

Section: Immune-inflammation and Oxidative Stress Induced By Vesicantmentioning

confidence: 99%

Impact of melatonin effects on toxicology of vesicant chemical warfare agents: When science meets reality

Romero¹,

Gil‐Martín²,

Rı́os³

et al. 2020

Melatonin Res.

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In this review we focused our attention on sulfur mustard [bis(2-chloroethyl) sulphide], the main vesicant chemical warfare agent (CWA), which has been widely used in different military conflicts, including World War I and the Iran-Iraq war. Moreover, the evolution of the recent Iraq and Syria conflicts suggests that terrorist groups are aware of the significant psychological and media effects that would be produced by the mere attempt to use CWAs. Sulfur mustard can produce the alkylation of macromolecules bearing sulfhydryl groups, such as DNA and proteins. This vesicant can also generate free radicals which can develop toxicity in the areas exposed, such as the eyes, skin, respiratory tract (inhalation) and gastrointestinal tract (ingestion). In this respect, we advance and propose three salvage mechanisms through which a broad-spectrum multipotent molecule, melatonin, could facilitate neutralization of the toxic damage induced by sulfur mustard radical scavenging. We also speculate that the long-term effects of varying severity can appear after acute poisoning. Besides, melatonin-based therapy strategies can modulate of epigenetic mechanisms and become very suitable for the clinical treatment of victimized patients. However, the utilization of melatonin as a “therapeutic bullet” addressed to counteract the vesicant CWAs needs much additional in vitro research as well as systematic animal studies and controlled translational trials.

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Section: Immune-inflammation and Oxidative Stress Induced By Vesicantmentioning

confidence: 99%

Impact of melatonin effects on toxicology of vesicant chemical warfare agents: When science meets reality

Romero¹,

Gil‐Martín²,

Rı́os³

et al. 2020

Melatonin Res.

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“…The use of the progressive motility of animal-derived spermatozoa as a method to identify the toxic effects of substances has been previously implemented [18][19][20]. The toxic effects by substances on human spermatozoa motility have been likewise reported [21][22][23][24]. However, the availability of robust human motility test systems that allow for a broad and serial substance evaluation for putative toxic effects on mitochondrial function is limited.…”

Section: Introductionmentioning

confidence: 99%

Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type

Vollmer

Stegmayr

2022

Toxins

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The syndrome of uremic toxicity comprises a complex toxic milieu in-vivo, as numerous uremic substances accumulate and harm the organ systems. Among these substances, toxic and non-toxic players differently interfere with human cells. However, results from animal experiments are not always compatible with the expected reactions in human patients and studies on one organ system are limited in capturing the complexity of the uremic situation. In this narrative review, we present aspects relevant for cellular toxicity research based on our previous establishment of a human spermatozoa-based cell model, as follows: (i) applicability to compare the effects of more than 100 uremic substances, (ii) detection of the protective effects of uremic substances by the cellular responses towards the uremic milieu, (iii) inclusion of the drug milieu for cellular function, and (iv) transferability for clinical application, e.g., hemodialysis. Our technique allows the estimation of cell viability, vitality, and physiological state, not only restricted to acute or chronic kidney toxicity but also for other conditions, such as intoxications of unknown substances. The cellular models can clarify molecular mechanisms of action of toxins related to human physiology and therapy. Identification of uremic toxins retained during acute and chronic kidney injury enables further research on the removal or degradation of such products.

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“…In addition, some studies have shown that SM can disrupt sex hormones, and induce a variety of structural and functional disorders in the male reproductive system post exposure. 18 19 How these changes affect fertility among those who survived SM exposure is, however, still unclear. 19–21 Moreover, in a study among SM survivors (males and females) almost 15 years after exposure to SM, no increased infertility was observed.…”

Section: Introductionmentioning

confidence: 99%

Gendered lived experiences of marriage and family following exposure to chemical warfare agents: content analysis of qualitative interviews with survivors in Halabja, Kurdistan-Iraq

Moradi

Söderberg

et al. 2020

BMJ Open

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ObjectiveTo study gendered experiences of the long-term effects of a chemical warfare agent (CWA; sulfur mustard).DesignQualitative face-to-face semi-structured in-depth interview study using content analysis approach with thematic analysis and anthropological inquiries.SettingThe city of Halabja in the Kurdistan Region of Iraq.ParticipantsSurvivors of CWA (n=16, female:male 10:6, mean age 45.5 years (range 34 to 67)) with lung damage diagnosis and with a range of sociodemographic variables.ResultsLatent content was expressed as: To get or not to get married? Two categories—social abandonment and uncertain marriage—emerged as expressions of the manifest content. The majority of the participants showed uncertainty as a central concern that affects all decision-making in their private and social life. Uncertainty over marriage and family were huge, corresponding to their fear of giving birth to children with congenital birth defects. Exposure to CWAs was conceptualised in terms of stigmatised illnesses, and consequently resulted in loneliness and social isolation, leading to negative impacts on other aspects of professional and social life. The results demonstrated a gendered pattern: CWA-exposed women were more affected psychosocially than CWA-exposed men. More CWA-exposed women were unemployed, divorced or single, or lived under vulnerable circumstances compared with men.ConclusionSurvivors of CWA exposure have developed a sense of gendered uncertainty around getting married and building a family. Sulfur mustard-exposed women, in particular, long to be desired in the community as they face social exclusion. Survivors should be provided evidence-based consultancy to optimise their decision-making around marriage and other social and family challenges.

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Cellular and molecular mechanisms of sulfur mustard toxicity on spermatozoa and male fertility

Abstract: Sulfur mustard (SM) is a toxic compound that can target human spermatozoa.

Cited by 7 publications

References 70 publications

Impact of melatonin effects on toxicology of vesicant chemical warfare agents: When science meets reality

Impact of melatonin effects on toxicology of vesicant chemical warfare agents: When science meets reality

Establishing Cell Models to Understand Cellular Toxicity: Lessons Learned from an Unconventional Cell Type

Gendered lived experiences of marriage and family following exposure to chemical warfare agents: content analysis of qualitative interviews with survivors in Halabja, Kurdistan-Iraq

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