Aquaporin 11-Dependent Inhibition of Proliferation by Deuterium Oxide in Activated Hepatic Stellate Cells

Lee, Phil Jun; Park, Hye-Jin; Cho, Namki

doi:10.3390/molecules23123209

Cited by 8 publications

(8 citation statements)

References 27 publications

(37 reference statements)

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“…First indications suggest that Aquaporin-11 is relevant for the transmission of the effect. 31 In sum, in tumors with a high sensitivity towards D 2 O an exchange of normal water by D 2 O may be therapeutic option particularly in combination with other measures.…”

Section: Discussionmentioning

confidence: 99%

<p>Heavy Water Affects Vital Parameters of Human Melanoma Cells in vitro</p>

Kleemann¹,

Reichenbach²,

Zöller³

et al. 2020

CMAR

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Although regular water is composed of two hydrogens and one oxygen, referred to as H 2 O, a small amount of water on this planet contains alternative forms of elements with different molecular weights because of the addition of neutrons. The present study was dedicated to studying the effect of heavy water (D 2 O), in which the two hydrogens become substituted by deuterium, on the cell physiology of different human cells with particular focus on malignant melanoma cells. Methods: Cells were cultured in regular medium in which the content of H 2 O was gradually substituted by D 2 O or deuterium-depleted water (DDW). Following this, the changes of basic cellular parameters, such as morphology, migration, proliferation, cell cycle, apoptosis and microtubule integrity were examined. Results: It was found that raising the D 2 O content above the standard levels led to a concentration-dependent decrease in proliferation. Lowering the D 2 O levels below this level had no effect. Likewise, elevated D 2 O levels hampered migration. Moreover, cell-cycle analysis showed an increase of sub-G1 cells. Corroboratively, markers for apoptosis were induced (histone-associated DNA fragments, Bax, and PARP). In regard to microtubule integrity, only very high levels of D 2 O (75%) caused partial filament condensation. Conclusion: D 2 O, although chemically identical with H 2 O, shows proapoptotic and antiproliferative effects on melanoma cells. These findings give a closer look of this interesting compound.

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Section: Discussionmentioning

confidence: 99%

<p>Heavy Water Affects Vital Parameters of Human Melanoma Cells in vitro</p>

Kleemann¹,

Reichenbach²,

Zöller³

et al. 2020

CMAR

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“…[6][7][8][9] Heme oxygenase (HO) is a cytoprotective protein with an ability to confer a beneficial effect on normal cells. 10 It mainly functions as a rate-limiting enzyme in heme degradation, yielding carbon monoxide (CO), iron, and biliverdin as the end products. 11 HO-1 and HO-2 are isoforms of HO in mammals.…”

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confidence: 99%

Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

Lee

Park

Yoo

et al. 2019

Natural Product Communications

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A key pathologic event in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, is endoplasmic reticulum (ER) stress-induced neuronal cell death. ER stress-induced generation of reactive oxygen species (ROS) has been implicated in neurological disease processes. Betulin is one of the major triterpenoids found in Betula platyphylla that possesses several biological properties, including cytoprotective and antioxidative effects. Therefore, we investigated whether betulin could prevent ER stress-induced neurotoxicity in HT-22 hippocampal neuronal cells. We observed that betulin reduced the thapsigargin (TG, an ER stress inducer)-induced apoptosis of HT-22 cells. Moreover, the cytoprotective effects of betulin were comparable to those of tauroursodeoxycholic acid, a potent ER stress-reducing agent. In our study, we confirmed that the ER stress-induced accumulation of ROS plays an important role in HT-22 cell death. Betulin also displayed cytoprotective effects in TG-injured HT-22 cells by reducing ROS generation; these results were comparable to those for N-acetyl-L-cysteine, a known ROS inhibitor. In addition, SnPP, a heme oxygenase-1 (HO-1) inhibitor significantly blocked the cytoprotective effects and ROS scavenging activity of betulin. Based on these results, we believe that betulin-mediated induction of HO-1 may contribute to the neuroprotective effects against ER stress in HT-22 hippocampal cells. We also found that betulin significantly inhibited the TG-induced expression of CHOP and caspase-12. These results demonstrated that betulin could serve as a potential therapeutic agent against ER stress-induced neurodegenerative diseases.

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“…It has previously been shown that using DDW accelerates metabolism, intracellular processes associated with the inhibition of oxidative stress development under various pathological conditions in vitro [27,[49][50][51]. Since oxidative stress is a major pathophysiological factor in the development of obesity and the progression of obesity-related complications, we hypothesized that DDW may also alleviate these conditions.…”

Section: Discussionmentioning

confidence: 98%

Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats

et al. 2019

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In this study, we present the potential application of deuterium-depleted water (DDW) for the prevention and adjuvant treatment of obesity in rats. We tested the hypothesis that DDW can alleviate diet-induced obesity (DIO) and its associated metabolic impairments. Rats fed a high-fat diet had an increased body weight index (BWI), glucose concentration, and level of certain proinflammatory cytokines; decreased levels of insulin in the serum; decreased tryptophan and serotonin in the brain, and a decreased concentration of some heavy metals in the liver. Drinking DDW at a concentration of 10 ppm deuterium/protium (D/H) ad libitum for 3 weeks restored the BWI, glucose (serum), tryptophan (brain), and serotonin (brain) levels and concentration of Zn in the liver in the DIO animals to those of the controls. The levels of proinflammatory cytokines (IL-1β, IL-6, IFNγ) and anti-inflammatory TNFα were decreased in DIO rats, while anti-inflammatory cytokine (IL-4, IL-10) levels remained at the control levels, which is indicative of a pathophysiological syndrome. In contrast, in groups of rats treated with DDW, a significant increase in anti-inflammatory (IL-4, IL-10) and proinflammatory cytokines (IFNγ) was observed. This finding indicates a reduction in systemic inflammation in obese animals treated with DDW. Similarly, the high-fat diet caused an increased level of oxidative stress products, which was accompanied by decreased activity of both superoxide dismutase and catalase, whereas the administration of DDW decreased the level of oxidative stress and enhanced antioxidant enzyme activities.Molecules 2020, 25, 23 2 of 15 the development of new, safer and more effective pharmaceutical approaches for obesity treatment is essential.Natural water is a mixture of molecules containing stable isotopes 16 O, 17 O, 18 O, 1 H, and 2 H. The ratio of deuterium atoms to protium (D/H) in fresh and marine water is 132-156 µg/g (ppm) [7,8].Since the mass of protium H is half of the mass of deuterium D, effects arising from the replacement of isotopes influence biological systems; for example, the rates of chemical reactions between substances containing these isotopes may differ by a factor of 5-10 [9-11].Numerous publications over the last 20 years have been devoted to the study of the role of deuterium in natural (150 ppm) or reduced content in the human body [12]. It has been shown that deuterium-depleted water (DDW) exhibits antidotal properties with individual and combined effects on the dosage of pharmaceutical substances and auxiliary substances [13][14][15][16]. The mechanisms of such influence are due to the structure, physicochemical properties of DDW [17] and changes in ligand-receptor interactions in biological objects of different hierarchical levels [18]. DDW increases the rate of photosynthesis and promotes the growth of plants and aquatic animals [19,20]. In Europe, the USA, Japan, China and Russia, DDW is used for prophylactic and therapeutic purposes [21,22]. Currently, DDW is using as an adjuvant in cancer treatment ...

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Aquaporin 11-Dependent Inhibition of Proliferation by Deuterium Oxide in Activated Hepatic Stellate Cells

Cited by 8 publications

References 27 publications

<p>Heavy Water Affects Vital Parameters of Human Melanoma Cells in vitro</p>

<p>Heavy Water Affects Vital Parameters of Human Melanoma Cells in vitro</p>

Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

Deuterium-Depleted Water as Adjuvant Therapeutic Agent for Treatment of Diet-Induced Obesity in Rats

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