A new Thiocyanoacetamide protects rat sperm cells from Doxorubicin-triggered cytotoxicity whereas Selenium shows low efficacy: In vitro approach

• Published in: Toxicology in vitro 2019-12, Vol.61, p.104587-104587, Article 104587
• Main Authors: Boussada, Marwa, Ali, Ridha Ben, Chahbi, Ahlem, Abdelkarim, Mohamed, Fradj, Mohamed Kacem Ben, Dziri, Chadli, Bokri, Khouloud, Akacha, Azaiez Ben, El May, Michèle Véronique
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacology; Animals; Anticancer properties; Antineoplastic Agents - toxicity; Cell death; Cell survival; Cell Survival - drug effects; Chemotherapy; Cytotoxicity; Damage assessment; Data collection; Deoxyribonucleic acid; DNA; DNA damage; Doxorubicin; Doxorubicin - toxicity; Fatty acids; Fatty Acids - metabolism; Flow cytometry; Gas chromatography; Germ cells; Glucose; Glucose - metabolism; Lipid peroxidation; Lipids; Male; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Oxygen consumption; Oxygen Consumption - drug effects; Peroxidation; Protective Agents - pharmacology; Rats, Wistar; Selenium; Selenium - pharmacology; Sperm; Sperm Motility - drug effects; Spermatozoa - drug effects; Spermatozoa - physiology; Superoxide; Time dependence; Toxicity
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2019.06.021

Doxorubicin (DOX) exhibits a wide-ranging spectrum of antitumor activities which maintain its clinical use despite its devastating impact on highly proliferating cells. The present work was designed to develop a new approach which aims to protect male germ cells from DOX cytotoxicity. Thus, an assessment of the protective potential of a new thioamide analog (thiocyanoacetamide; TA) compared to selenium (Se) was performed in rat sperms exposed to DOX in vitro. Oxygen consumption rate (OCR) was measured after exposure to three different doses (0.5, 1, 1.5 and 2 μM) of DOX, Se or TA, and the suitable concentrations were selected for further studies afterwards. Motility, OCR in a time-dependent manner, glucose extracellular concentration and lipid peroxidation (LPO) were measured. Fatty acid (FA) content was assessed by gas chromatography (GC-FID). Cell death, superoxide anion (O2−), mitochondrial membrane potential (MMP), and DNA damage were evaluated by flow cytometry. TA association with DOX increased OCR and glucose uptake, improved cell survival and decreased DNA damage. The co-administration of DOX with Se increased OCR, significantly prevented O2− overproduction, and decreased LPO. Collected data brought new insights regarding this transformed TA, which showed better efficiency than Se in reducing DOX cytotoxic stress in sperms. •A new thioamide reduces doxorubicin-mediated sperm death.•Doxorubicin association with selenium promotes DNA damage in rat sperms.•Doxorubicin inhibit oxygen consumption in isolated sperms.