Curcumin attenuates Mancozeb-induced toxicity in rat thymocytes through mitochondrial survival pathway

Pavlović, Voja; Cekić, Sonja; Ćirić, Miroslav; Krtinić, Dane; Jovanović, Jelena

doi:10.1016/j.fct.2015.12.029

Cited by 16 publications

(19 citation statements)

References 44 publications

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“…Changes in the mitochondrial membrane potential (MMP) in platelets were evaluated using the lipophilic cation Rhodamine 123, as previously described [14]. The fluorescence of Rhodamine 123 in the cells was determined by flow cytometry.…”

Section: Parameter Analysismentioning

confidence: 99%

Evaluation of platelet activation during storage in leukocyte-depleted platelet concentrates

Vučić

Stanojkovic²,

Antić³

et al. 2017

Bosn J of Basic Med Sci

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Structural and functional changes in platelets during storage can lead to the loss of platelet reactivity and response. Our aim was to evaluate leukocyte-depleted platelet concentrates on storage days 0, 3 and 5, obtained by in-line filtration. In non-filtered platelet concentrates (NF-PC) group, 180 whole blood units were collected with quadruple blood bags and then compared to another group of 180 whole blood units (leukocyte-depleted platelet concentrates [LD-PC]), collected in Imuflex Whole Blood Filter Saving Platelets (WB-SP) bags with an integrated leukoreduction filter, with regard to the platelet quality and characteristics. The efficacy of the two techniques for platelet concentrate preparation was evaluated by white blood cell (WBC) and platelet count on day 0. The partial pressure of oxygen (pO2), pH, platelets positive for P-selectin (CD62P), CD63, cluster of differentiation 42b (CD42b), phosphatidylserine (PS), and mitochondrial membrane potential (MMP) were analyzed during the storage in both groups. A significantly lower WBC count and higher platelet count was observed in LD-PC compared to NF-PC group, indicating the overall efficacy of the first technique. During the 5-day storage, pH and pO2 decreased in both groups. In LD-PC group, higher pH, increased pO2 and decreased platelet surface expression of CD62P, CD63 and PS were observed compared to NF-PC group. In both groups, the percentage of CD42b positive platelets and MMP did not change significantly during the 5-day period. The assessment of different markers of platelet activation may be an effective tool in evaluating the quality of platelets during storage. A better understanding of platelet activation may provide new insights for developing a novel therapeutic approach in the manipulation of platelet aggregation.

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Section: Parameter Analysismentioning

confidence: 99%

Evaluation of platelet activation during storage in leukocyte-depleted platelet concentrates

Vučić

Stanojkovic²,

Antić³

et al. 2017

Bosn J of Basic Med Sci

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“…In addition, it can react with the sulfhydryl groups of amino acids and enzymes in fungal cells, resulting in metabolism disorders and activated apoptotic pathways [4]. Although it has been reported to possess low acute toxicity and scarce persistence in the environment, diverse chronic adverse health effects of mancozeb have been reported, such as increased carcinogenic potential [5], endocrine system disruption, and toxic effects on the immune [6] and neuronal system [7]. …”

Section: Introductionmentioning

confidence: 99%

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Liu

Wang

et al. 2016

Oncotarget

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Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

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“…Isolated rat thymocytes were cultured in 96-well round-bottom plates (NUNC, Aarhus, Denmark). Each plate well contained 100 μl of cell suspension (5 × 10 5 cells), as we described previously [16]. The cells were treated with ketamine (100 µM) with or without increasing concentrations of curcumin (0.3, 1, and 3 μM), for 24 hours.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

“…The final DMSO concentration never exceeded 0.5% (v/v). Cultivation with the increasing concentrations of curcumin (0.3, 1, and 3 μM) was chosen based on our earlier reports [16,23], as well as based on another study which demonstrated that 3 μM was the highest concentration of curcumin that did not induce any cytotoxic effect in rat thymocytes [24].…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway

Pavlović

Jović

Karan

et al. 2018

Bosn J of Basic Med Sci

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Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 μM) for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS) production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 μM) with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin.

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Curcumin attenuates Mancozeb-induced toxicity in rat thymocytes through mitochondrial survival pathway

Cited by 16 publications

References 44 publications

Evaluation of platelet activation during storage in leukocyte-depleted platelet concentrates

Evaluation of platelet activation during storage in leukocyte-depleted platelet concentrates

Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes

Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway

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