Work

Effect of the cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid on in vivo platelet activation, oxidative stress, and procoagulant responses induced by waterpipe smoke exposure in mice

Year: 2026

Type: article

Abstract: Introduction Exposure to waterpipe smoke (WPS) in humans and experimental animals has been reported to cause oxidative stress and thrombotic complications. L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione (GSH) in tissues. Nevertheless, the possible mitigating effects of OTC on platelet aggregation induced by WPS inhalation, and its underlying mechanisms of action remain unexplored. This is the goal of the present work in BALB/c mice. Methods Animals were exposed to either WPS or air (control) by inhalation daily for 30 min for 1 month. OTC was given 1 h before each exposure session by gavage at a dose of 80 mg/kg. Results WPS inhalation increased various markers of platelet aggregation, coagulation, fibrinolysis and endothelial integrity (platelet factor 4, tissue factor, fibrinogen, thrombin-antithrombin complexes, plasminogen activator inhibitor, P-selectin, E-selectin, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1). It also shortened the prothrombin time and partial thromboplastin time and augmented the plasma concentrations of C-reactive protein and triglycerides. All these effects were attenuated by OTC treatment. Likewise, OTC administration significantly mitigated platelet aggregation in vivo . Platelets isolated from mice exposed to WPS showed high levels of markers of oxidative and nitrosative stress, calcium, annexin V and calpain. The latter effects were significantly alleviated by OTC treatment. Discussion Our data show that OTC administration significantly mitigated WPS-induced in vivo endothelial injury and thrombotic events, as well as platelet oxidative stress and apoptosis. This finding provides evidence on the mechanisms of toxicity of WPS on platelet physiology, and the alleviative action of OTC.

Source: Frontiers in Toxicology

DOI: 10.3389/ftox.2026.1696863

Authors: Sumaya Beegam, Nur. E. Zaaba, Ozaz Elzaki, Javed Yasin, Badreldin H. Ali, Abderrahim Nemmar

Institution: United Arab Emirates University

Language: English

Topic: Platelet Disorders and Treatments

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,077