Hydrogen sulfide protects H9c2 cardiomyoblasts against H2O2-induced apoptosis

Ngowi

et al. 2021

IJMS

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

Section: Role Of H 2 S In Vascular Functionmentioning

confidence: 99%

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases

Ngowi

et al. 2021

IJMS

“…Since mitochondrial function is highly sensitive to oxidative damages [25] and to further verify whether mitochondrial apoptosis pathway is induced by compounds A and B, the mitochondrial membrane potential (MMP) was assessed using the fluorescent dye JC-1. Red fluorescence displaying the matrix of actively respiring mitochondria is the aggregate form of JC-1 molecules, while green fluorescence is emitted from the monomeric form of the JC-1 molecules indicating mitochondrial membrane depolarization.…”

Section: Compounds a And B Influenced Mitochondrial Potential Membranementioning

confidence: 99%

Two novel anticancer compounds with minimum cardiotoxic property

Afsharirad

Tahmasvand

Amini

et al. 2020

BMC Pharmacol Toxicol

Background Although two novel synthesized compounds with tri-aryl structures; 3-(4-chlorophenyl)-5-(4-fluorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (A) and 3,5-bis-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1,2,4-oxadiazole (B) have been previously demonstrated to possess remarkable anti-breast cancer activity, their cardiotoxicity remains a major concern due to their mechanism of action. To address this concern, we assessed the ability of these compounds to cause toxicity towards H9c2 cardiomyocytes as an in vitro model of cardiotoxicity. Methods Cytotoxic activity of both compounds was explored in vitro on H9c2 cells using MTT assay. Annexin V/PI method, intracellular ROS determination and mitochondrial membrane potential assay were applied to elucidate the mechanism of action of the cell death. Results MTT assay revealed a concentration- and time-dependent cardiotoxicity. Findings of apoptosis by double staining with annexin V and propidium iodide divulged no cell death including apoptosis and necrosis at the concentration that were effective to inhibit cancer cells proliferation (10 μM) at 24 and 48 h. Furthermore, flow cytometric measurement of membrane potential and ROS determination using DCFH-DA verified the safe concentration of the compounds against H9c2 cells with no cardiotoxic effect. However, the higher concentration of the compounds could induce cell death through ROS-mediated mitochondrial dysfunction. Conclusions Altogether, the results represented two novel chemical molecules possessing anti-breast cancer activity with minimum cardiac side effect.

“…Since mitochondrial function is highly sensitive to oxidative damages [25] and to further verify whether mitochondrial apoptosis pathway is induced by compounds A and B, the mitochondrial membrane potential (Δψm) was assessed using the uorescent dye JC-1. Red uorescence displaying the matrix of actively respiring mitochondria is the aggregate form of JC-1 molecules, while green uorescence is emitted from the monomeric form of the JC-1 molecules indicating mitochondrial membrane depolarization.…”

Section: Compounds a And B In Uenced Mitochondrial Potential Membranementioning

confidence: 99%

Two novel anticancer compounds with minimum cardiotoxic property

Afsharirad

Tahmasvand

Amini

et al. 2020

Preprint

Background: Although two novel synthesized compounds with tri-aryl structures (A and B) have been previously demonstrated to possess remarkable anti-breast cancer activity, their cardiotoxicity remains a major concern due to their mechanism of action. To address this concern, we assessed the ability of these compounds to cause toxicity towards H9c2 cardiomyocytes as an in vitro model of cardiotoxicity. Methods: Cytotoxic activity of both compounds was explored in vitro on H9c2 cells using MTT assay. Annexin V/PI method, intracellular ROS determination and mitochondrial membrane potential assay were applied to elucidate the mechanism of action of the cell death. Results: MTT assay revealed a concentration- and time-dependent cardiotoxicity. Findings of apoptosis by double staining with annexin V and propidium iodide divulged no cell death including apoptosis and necrosis at the concentration that were effective to inhibit cancer cells proliferation (10 µM) at 24 and 48 hours. Furthermore, flow cytometric measurement of membrane potential and ROS determination using DCFH-DA verified the safe concentration of the compounds against H9c2 cells with no cardiotoxic effect. However, the higher concentration of the compounds could induce cell death through ROS-mediated mitochondrial dysfunction. Conclusions: Altogether, the results represented two novel chemical molecules possessing anti-breast cancer activity with minimum cardiac side effect.