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

Toxicol In Vitro. 2019 Dec:61:104587. doi: 10.1016/j.tiv.2019.06.021. Epub 2019 Jul 2.

Abstract

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.

Keywords: Chemotherapy; DNA; Fatty acids; Mitochondria; Oxygen consumption; Sperm.

MeSH terms

  • Acetamides / pharmacology*
  • Animals
  • Antineoplastic Agents / toxicity*
  • Cell Survival / drug effects
  • Doxorubicin / toxicity*
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Oxygen Consumption / drug effects
  • Protective Agents / pharmacology*
  • Rats, Wistar
  • Selenium / pharmacology*
  • Sperm Motility / drug effects
  • Spermatozoa / drug effects*
  • Spermatozoa / physiology

Substances

  • Acetamides
  • Antineoplastic Agents
  • Fatty Acids
  • Protective Agents
  • Doxorubicin
  • Selenium
  • Glucose