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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.

Despite its deleterious effect on healthy cells and highly regenerating cells such as spermatozoa, Doxorubicin (DOX) is still one of the most used anticancer drugs in the last decades. The present work aimed to investigate the ability of the selenium (Se) and the thiocyanoacetamide (T) to reduce DOX toxicity in gonad. Adult male rats were treated with DOX intravenously (i.v.) at 3.7mg/kg/week associated with Se intragastrically (i.g.) at 0.2mg/kg/day or with T at 10mg/kg/day i.g. After 47days of treatment, sperm quality, biochemical parameters, blood cell count and histological changes in liver, testis and epididymis were assessed. The results showed a poor sperm quality, a perturbation of ionic stability and a significant alteration of lipid metabolism and hematological parameters after the sub-chronic administration of DOX. In testis, DOX exerted serious epithelium damage and numerous seminiferous tubules did not present a normal spermatogenesis. In epididymis, epithelium was altered and mastocytes infiltrated the interstitium. DOX did not exert any significant change in liver except dilatations of sinusoid capillaries. DOX association with Se or T reduced its toxicity on some hematological and biochemical parameters. Both combined treatment improved sperm quality and partially restored spermatogenesis as well as testis and epididymis' normal aspect. These findings brought new sights regarding the effect of Se and a new derivative of T in a combined treatment with DOX on germ cells, gonad and liver. The support of these relevant outcomes with further in vitro studies is necessary to highlight the accurate process involved in Se or T protection against DOX induced damages.

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.