The Implication of Low Dose Dimethyl Sulfoxide on Mitochondrial Function and Oxidative Damage in Cultured Cardiac and Cancer Cells

Abstract

Although numerous studies have demonstrated the biological and multifaceted nature of dimethyl sulfoxide (DMSO) across different in vitro models, the direct effect of “non-toxic” low DMSO doses on cardiac and cancer cells has not been clearly explored. In the present study, H9c2 cardiomyoblasts and MCF-7 breast cancer cells were treated with varying concentrations of DMSO (0.001–3.7%) for 6 days. Here, DMSO doses < 0.5% enhanced the cardiomyoblasts respiratory control ratio and cellular viability relative to the control cells. However, 3.7% DMSO exposure enhanced the rate of apoptosis, which was driven by mitochondrial dysfunction and oxidative stress in the cardiomyoblasts. Additionally, in the cancer cells, DMSO (≥0.009) led to a reduction in the cell’s maximal respiratory capacity and ATP-linked respiration and turnover. As a result, the reduced bioenergetics accelerated ROS production whilst increasing early and late apoptosis in these cells. Surprisingly, 0.001% DMSO exposure led to a significant increase in the cancer cells proliferative activity. The latter, therefore, suggests that the use of DMSO, as a solvent or therapeutic compound, should be applied with caution in the cancer cells. Paradoxically, in the cardiomyoblasts, the application of DMSO (≤0.5%) demonstrated no cytotoxic or overt therapeutic benefits.

N‐acetylcysteine attenuates oxidative stress‐mediated cell viability loss induced by dimethyl sulfoxide in cryopreservation of human nucleus pulposus cells: A potential solution for mass production

“…In adipocytes, for example, DMSO at concentrations ≥1% for 1 h reduced cell viability and accelerated cellular apoptosis by increasing mitochondrial membrane potential and ROS 42 . Elsewhere, in cardiomyoblasts and in breast cancer cells, 3.7% DMSO exposure for 6 days induced apoptosis driven by mitochondrial dysfunction and oxidative stress 44 . Finally, exposure of astrocytes to 5% DMSO for 24 h caused cell viability loss and mitochondrial integrity disruption, membrane potential impairment, ROS production, and subsequent cytochrome C release and caspase‐3 activation 45 .…”

“… 42 Elsewhere, in cardiomyoblasts and in breast cancer cells, 3.7% DMSO exposure for 6 days induced apoptosis driven by mitochondrial dysfunction and oxidative stress. 44 Finally, exposure of astrocytes to 5% DMSO for 24 h caused cell viability loss and mitochondrial integrity disruption, membrane potential impairment, ROS production, and subsequent cytochrome C release and caspase‐3 activation. 45 Consistent with these previous reports, we demonstrated that DMSO increases intracellular and mitochondrial ROS in NPC in a dose‐dependent manner.…”

“…Moreover, in mass production of cellular products, when a large volume of cells is cryopreserved at one time, it is inevitable that they are exposed to the cryopreservation medium at harmful temperatures for a certain period of time. This is a critical consideration because dimethyl sulfoxide (DMSO) is the most commonly used cryoprotective agent to prevent intracellular ice formation and has been reported to cause cytotoxicity via elevated oxidative stress and mitochondrial dysfunction 41–45 . Moreover, multiple studies of other cell types have highlighted the involvement of reactive oxygen species (ROS) as being involved in the detrimental effects of DMSO on cell viability 45 .…”

“…This is a critical consideration because dimethyl sulfoxide (DMSO) is the most commonly used cryoprotective agent to prevent intracellular ice formation and has been reported to cause cytotoxicity via elevated oxidative stress and mitochondrial dysfunction. 41 , 42 , 43 , 44 , 45 Moreover, multiple studies of other cell types have highlighted the involvement of reactive oxygen species (ROS) as being involved in the detrimental effects of DMSO on cell viability. 45 While the direct effects of DMSO on human NPC have not been clarified, oxidative stress has been shown to impede NPC proliferation, promote cell senescence, and promote a catabolic phenotype.…”

Redox Active Molecules in Cancer Treatments

“… Natural plant compounds (naringenin [ 3 ], papaverine [ 4 ], polyphenols isolated from Myrciaria trunciflora [ 5 ] or Anneslea fragrans [ 6 ], and seed-derived peptides [ 7 ]), natural compounds also found in animals (melatonin [ 2 , 8 ]), and peptides as well as proteins from Jellyfish venom [ 9 ]. Synthetic compounds, i.e., alkyl thiols [ 10 ], dimethyl sulfoxide [ 11 ], metformin and S63845 [ 12 ], the ruthenium complex [Ru(Phen) 3 ] 2+ [ 13 ], and copper-based compounds—Casiopeinas [ 14 ]. Different formulations, i.e., peptide fractions from germinated soybeans conjugated to Fe 3 O 4 nanoparticles [ 15 ] and astaxanthin microparticles in combination with pentoxifylline [ 16 ].…”