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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.

This study aimed to explore the analgesic, antioxidant, behavioral and toxicological effects of 3,5-diaminopyrazole and thiocyanoacetamide. Caffeine was used as reference drug whose effects are known after oral treatment with an efficient dose (10mg/kg/day) for 30days. The preliminary bioassays indicated that both compounds at this dose have strong antioxidant capacities and present highly analgesic effects. The behavioral study showed an activation of the rat memory by thiocyanoacetamide. This molecule caused a phobia state to open areas in the elevated plus maze and specifically agoraphobia in the open field with a lack in the development of the exploratory capacity. 3,5-Diaminopyrazole caused memory troubles in rats that forgot the pathway to the exit from the maze, and induced an anxiety state revealed by immobility in closed arms of the elevated plus maze. All these observations were compared to the treatment by the known analgesic, caffeine, which increased the state of vigilance of the rats and developed their exploratory capacity. The chronic treatment with the investigated compounds showed no sign of toxicity with the absence of effect on the body and organ weights, blood count, kidney and liver function and histology. 3,5-Diaminopyrazole and thiocyanoacetamide have potent antioxidant and analgesic activities that are higher than caffeine with a safety profile. The chronic treatment by thiocyanoacetamide activated the memory and caused an emotional state of agoraphobia, but 3,5-diaminopyrazole caused a memory impairment and an emotional state of anxiety. Thus, the present study warrants further investigations involving these novel molecules for a possible development of new strong analgesic and antioxidant drugs which have an effect on the memory capacity.