Induction of cytotoxicity of Pelagia noctiluca venom causes reactive oxygen species generation, lipid peroxydation induction and DNA damage in human colon cancer cells

<p>Abstract</p> <p>Background</p> <p>The long-lasting and abundant blooming of <it>Pelagia noctiluca </it>in Tunisian coastal waters compromises both touristic and fishing activities and causes substantial economic losses. Determining their molecular mode of action is, important in order to limit or prevent the subsequent damages. Thus, the aim of the present study was to investigate the propensity of <it>Pelagia noctiluca </it>venom to cause oxidative damage in HCT 116 cells and its associated genotoxic effects.</p> <p>Results</p> <p>Our results indicated an overproduction of ROS, an induction of catalase activity and an increase of MDA generation. We looked for DNA fragmentation by means of the comet assay. Results indicated that venom of <it>Pelagia noctiluca </it>induced DNA fragmentation. SDS-PAGE analysis of <it>Pelagia noctiluca </it>venom revealed at least 15 protein bands of molecular weights ranging from 4 to 120 kDa.</p> <p>Conclusion</p> <p>Oxidative damage may be an initiating event and contributes, in part, to the mechanism of toxicity of <it>Pelagia noctiluca </it>venom.</p

Effects of Dichlorvos on cardiac cells: Toxicity and molecular mechanism of action

International audienceIn this study we aimed to understand the underlying mechanism of Dichlorvos-induced toxicity in cardiac cells. For this end, cells were treated by 170 μM of Dichlorvos (DDVP) (corresponding to the IC50) and molecular events were monitored by flow cytometry and western blotting. We have first demonstrated that cell exposure to DDVP for 24 h induced cell death by necroptosis. In fact, cell treatment with DDVP upregulated RIP1 expression and we have shown that chemical inhibition of RIP1 kinase activity by necrostatin-1 (Nec-1) greatly prevented from the induced cell death. Besides, we have demonstrated that, while there was no observed cell death following short exposure to DDVP (6 h), autophagy was enhanced, as proven by the increase in the level of both Beclin-1 and LC3-II and the accumulation of the CytoID® autophagy detection probe. Besides, when autophagy was inhibited by chloroquine (CQ) the percentage of necroptosis was significantly increased, suggesting that autophagy acts to protect cardiac cells against the toxicity induced by this pesticide. Concurrently, we have shown that the inhibition of the deacetylase sirtuin 1 (SIRT1) by EX527 or its knockdown by siRNA significantly increased DDVP-induced necroptosis, whereas when SIRT1 was activated by resveratrol (RSV) a significant decrease in DDVP-induced cell death was observed. In addition, we revealed that when the autophagy was inhibited by CQ, we can't reveal the protective effect of RSV anymore. Altogether, these results suggest that activation of SIRT1 protects cardiac cells from the toxicity of DDVP through an autophagy-dependent pathway

Factors associated with anxiety and depression in men undergoing fertility investigations: a cross-sectional study

Abstract Background Infertility is a real public health issue because of its medical, socio-cultural, and financial impact. It does also have heavy psychological consequences on both partners. This study aimed to assess levels of anxiety and depression among men undergoing infertility investigation and to identify their associated factors. Methods We conducted a cross-sectional study in the Laboratory of Cytogenetics and Reproductive Biology of Fattouma Bourguiba University Teaching Hospital (Monastir, Tunisia) between August 30th, 2020, and March 16th, 2021. Anxiety and depression levels were assessed using the valid Arab version of the Hospital Anxiety and Depression scale (HAD). Semen parameters were analyzed and interpreted according to 2021 World Health Organization (WHO) guidelines. Results A total of 282 men were included in the current study. The mean HAD-D (depression) and HAD-A (anxiety) scores were of 6.56 ± 3.07 (IQR [4–8]) and 7.94 ± 3.73 (IQR[5–10]) respectively. Univariate analysis showed that patients having two or more comorbidities were nearly five times more likely to be anxious than those without or with only one comorbidity (ORc = 4.71; p = 0.007). Furthermore, single patients were about four times more anxious than those in couple having primary or secondary infertility (ORc = 3.85; p = 0.027). With regards to semen parameters, patients having hypospermia were more than two times anxious compared with those with normal semen volume (ORc = 2.33; p = 0.034). As for depression, we observed that patients with an infertility history lasting for a year or more have a nine times greater risk of depression (ORc = 9.848; p = 0.007). With regards to semen parameters, patients exhibiting two or more semen abnormalities, teratozoospermia and increased MAI were more depressed (ORc = 2.478; p = 0.036; ORc = 2.549: p = 0.023; ORc = 2.762; p = 0.036). Furthermore, we found a negative correlation between HAD-A scores and patient’s age. Conclusions We pointed out through the current study the associated factors with anxiety and depression in patients under fertility management to precociously identify those who need psychological counseling and hence to better manage infertility issues

Triazole fungicide tebuconazole induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway

International audienceTebuconazole (TEB) is a common triazole fungicide that has been widely applied in the treatment of fungal diseases. It is reported that TEB could exert harmful effects on mammals’ health. However, the molecular mechanism involved in TEB toxicity remain undefined. Our study aimed to investigate the mechanisms of TEB-induced toxicity in intestinal cells. We found that TEB stimulates apoptosis through the mitochondrial pathway. Additionally, TEB triggers endoplasmic reticulum (ER) stress as demonstrated by the activation of the three arms of unfolded protein response (UPR). The incubation with the chemical chaperone 4-phenylbutyrate (4-PBA) alleviated ER stress and reduced TEB-induced apoptosis, suggesting that ER stress plays an important role in mediating TEB-induced toxicity. Furthermore, inhibition of ROS by N-acetylcysteine (NAC) inhibited TEB-induced ER stress and apoptosis. Taken together, these findings suggest that TEB exerts its toxic effects in HCT116 cells by inducing apoptosis through ROS-mediated ER stress and mitochondrial apoptotic pathway

Selective solid-phase extraction using a molecularly imprinted polymer for the analysis of patulin in apple-based foods

4noThe aim of this work was to evaluate the use of a molecularly imprinted polymer as selective solid-phase extraction sorbent for the clean-up and pre-concentration of patulin from apple-based food products. Ultra high pressure liquid chromatography coupled to ultraviolet absorbance detection was used for the analysis of patulin. The molecularly imprinted polymer was applied, for the first time, to the determination of patulin in apple juice, puree and jam samples spiked within the maximum levels specified by the European Commission No.1881/2006. High recoveries (>77%) were obtained. The method was validated and found to be linear in the range 2-100 μg kg(-1) with correlation coefficients greater than 0.965 and repeatability relative standard deviation below 11% in all cases. Compared with dispersive solid phase extraction (QuEChERS method) and octadecyl sorbent, the molecularly imprinted polymer showed higher recoveries and selectivity for patulin. The application of Affinisep molecularly imprinted polymer as a selective sorbent material for detection of patulin fulfilled the method performance criteria required by the Commission Regulation No. 401/2006, demonstrating the suitability of the technique for the control of patulin at low ppb levels in different apple-based foods such as juice, puree and jam samples.nonenoneLucci, Paolo; Moret, Sabrina; Bettin, Sara; Conte, LanfrancoLucci, Paolo; Moret, Sabrina; Bettin, Sara; Conte, Lanfranc