Spermatozoa are capable of producing small amounts of reactive oxygen species (ROS), and sperm in teratozoospermia generate more ROS than sperm in normozoospermia. The source of ROS production in ejaculated human sperm has not been fully clarified. Recently, NADPH oxidase 5 (NOX5) was detected in human sperm, and ROS generation by this enzyme was reported. We investigated the magnitude of NOX5 expression in normozoospermic (n = 12) and teratozoospermic (n = 13) semen samples with different percentages of abnormal sperm. The existence of NOX5 enzymes in sperm was analysed by immunocytochemistry and flow cytometry and correlated with morphological abnormalities. Immunofluorescent studies identified NOX5 in acrosomal, equatorial, post-acrosomal regions, the body and the tail of both normal and abnormal sperm. Teratozoospermic semen samples had higher percentages of NOX5-positive sperm and expressed more NOX5 (based on higher mean fluorescent intensity) than normal semen samples. Positive correlations were observed between abnormal sperm morphology and both the percentage of NOX5-positive sperm and the magnitude of NOX5 expression. Based on these findings, we can assume that there is a positive correlation between ROS generation in teratozoospermia and that in NOX5 expression.

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Abstract. 5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay. SW480 cells that express a mutated form of p53 and two other CRC cell lines were used, HCT116 and LS174T, with wild-type p53. To determine the effect of ACF on the sensitivity of cells to 5-FU, cells were co-treated with the 30% maximal inhibitory concentration (IC 30 ) of ACF and various concentrations of 5-FU, or pretreated with the IC 30 of ACF and various concentrations of 5-FU. To assess the mechanism of action of ACF, cells were treated with IC 30 values of the compound and then the reverse transcription-quantitative polymerase chain reaction was used to evaluate mRNA levels of hypoxia-inducible factor-1α (HIF-1α) and topoisomerase 2. Results indicate that pretreatment with ACF markedly sensitized CRC cells to the cytotoxic effects of 5-FU, whereas simultaneous treatment with ACF and 5-FU were not able to alter the resistance of CRC cells to 5-FU. In comparison with irinotecan, ACF was a more potent agent for enhancing the antitumor activity of 5-FU. ACF did not alter the mRNA levels of either HIF-1α or topoisomerase 2. The results of the present study reveal for the first time that pretreatment of CRC cells with ACF markedly increases the cytotoxic effects of 5-FU, regardless of the p53 status of cells.

Abstract

The current drug treatments against protozoan parasitic diseases including Chagas, malaria, leishmaniasis, and toxoplasmosis represent good examples of drug resistance mechanisms and have shown diverse side effects. Therefore, the identification of novel therapeutic strategies and drug compounds against such life-threatening diseases is urgent. According to the successful usage of selenium (Se) compounds-based therapy against some diseases, this therapeutic strategy has been recently further underlined against these parasitic diseases by targeting different parasite´s essential pathways. On the other hand, due to the important functions played by parasite selenoproteins in their biology (such as modulating the host immune response), they can be also considered as a novel therapeutic strategy by designing specific inhibitors against these important proteins. In addition, the immunomodulatory potentiality of these compounds to trigger T helper type 1 (Th1) cells and cytokinemediated immune response for the substantial induction of proinflammatory cytokines, thus, Se, selenoproteins, and parasite selenoproteins could be further investigated to find possible vaccine antigens. Herein, we collect and present the results of some studies regarding Se-based therapy against protozoan parasitic diseases and highlight relevant information and some viewpoints that might be insightful to advance toward more effective studies in the future.