Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver

Bayrak, Bertan Boran; Kulak, Gonul Yenidogan; Yanardağ, Refiye; Yarat, Ayşen

doi:10.1016/j.prp.2022.154186

Cited by 3 publications

(11 citation statements)

References 71 publications

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“…DDW refers to a variety of water with a lower D/(D+H) ratio than typical water. Many laboratory and clinical investigations have shown DDW ability to inhibit tumor growth [35,49,97,98]. Studies have indicated that the proliferation of cells and their ability to form colonies and invade are notably diminished by DDW.…”

Section: Discussionmentioning

confidence: 99%

Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis

Sharif¹,

Mandegary²,

Hassanzadeh³

2023

Preprint

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Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Accumulating clinical and experimental evidence suggests the role of cyclo-oxygenase (COX) enzymes in the pathogenesis of cancers including HCC. Deuterium-enriched water (DEW) and deuterium-depleted water (DDW) play a role both in the treatment and prevention of cancers. Combination therapy using COX-inhibitors and DDW/DEW could be a rational strategy to enhance the cytotoxicity of either agent in HCC. The cytotoxicity of celecoxib or indomethacin, alone and in combination with DDW or DEW was determined in the Hep-G2 HCC cell line by MTT assay. The COX-2, MAPK pathway proteins, the anti-apoptotic Bcl2 and pro-apoptotic Bax proteins, and caspase-3 activity were determined by SDS-PAGE and western blot. Co-treatment of selective and non-selective COX-2 inhibitors with DEW led to a remarkable increase in cytotoxicity and apoptosis of Hep-G2 cells. These events were associated with the activation of p38 and JNK MAPKs and a decrease in pro-survival proteins Bcl-2, COX-2, and ERK1/2. Furthermore, the combination therapy activated caspase-3, and the apoptosis mediator, and disabled poly ADP-ribose polymerase (PARP), the key DNA repair enzyme, by cleaving it. The combination of DEW with NSAIDs might be effective against HCC cells by influencing principal cell signaling pathways, and this has a potential to become a candidate for chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis

Sharif¹,

Mandegary²,

Hassanzadeh³

2023

Preprint

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“…Of the included studies, two were conducted in China [28,29], five in Hungary [19,[30][31][32][33], three in Iran [15,17,21], two in Romania [16,34], one in Sweden [18], one in Turkey [20], and one in Russia [35]. The studies identified were categorized into two types based on their subject: fourteen studies of the effect of DDW on cancer cell lines and animal cancer models [15][16][17][18][19][20][21][28][29][30][31][32]34,35] and one clinical study in humans [35].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…It was indicated that four upregulated proteins (paraoxonase 1 (PON1), reduced glutathione (GSH), catalase (CAT) and NQO1) and two downregulated proteins (myeloperoxidase (MPO) and xanthine oxidase (XO)) correlated with diminished ROS production. Furthermore, two downregulated proteins (lipid peroxidation (LPO) and sorbitol dehydrogenase (SDH)) decreased the risk of tumour occurrence [20]. Overall, four proteins were linked to affecting the proliferation and migration of tumours, and three proteins were related to regulating autophagy in cancer.…”

Section: Ddw Regulates the Expression Of Proteins In The Tumourmentioning

confidence: 99%

“…One study indicated that GSH, CAT and PON1 are upregulated, while GPX, GR, GST, MPO and XO are downregulated in the DDW treatment. The changes in those regulatory factors show an overall decreased number of ROS [20]. Additionally, the combination of auranofin and DDW therapy exhibited elevated ROS amounts, indicating an enhancement in the formation of ROS compared with monotherapy [18].…”

Section: Effects Of Ddw On the Cellular Redox Balance In The Tumourmentioning

confidence: 99%

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Deuterium-Depleted Water in Cancer Therapy: A Systematic Review of Clinical and Experimental Trials

Lu,

Chen

2024

Nutrients

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Chemotherapy exhibits numerous side effects in anti-tumour therapy. The clinical experiments indicated that deuterium-depleted water (DDW) monotherapy or in combination with chemotherapy was beneficial in inhibiting cancer development. To further understand the potential mechanism of DDW in cancer therapy, we performed a systematic review. The data from experiments published over the past 15 years were included. PubMed, Cochrane and Web of Science (January 2008 to November 2023) were systemically searched. Fifteen studies qualified for review, including fourteen in vivo and in vitro trials and one interventional trial. The results showed that DDW alone or in combination with chemotherapy effectively inhibited cancer progression in most experiments. The combination treatment enhances the therapeutic effect on cancer compared with chemotherapeutic monotherapy. The inhibitory role of DDW in tumours is through regulating the reactive oxygen species (ROS)-related genes in Kelch-like ECH-associated protein 1 (Keap 1) and Nuclear erythroid 2-related factor 2 (Nrf2) signalling pathways, further controlling ROS production. An abnormal amount of ROS can inhibit the tumour progression. More extensive randomized controlled trials should be conducted to evaluate the accurate effect of DDW in Keap1-Nrf2 signalling pathways.

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“…Liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase, glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase, and aspartate transaminase were studied. Compared with the tumor group consuming tap water, the DDW-consumed group reversed changes in all parameters except sialic acid, catalase, alanine transaminase, and aspartate transaminase [ 65 ].…”

Section: Effect Of D/h Shift On Proliferation and Apoptosis Of Tumor ...mentioning

confidence: 99%

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis

Yaglova

Timokhina

Обернихин

et al. 2023

IJMS

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Deuterium, a stable isotope of hydrogen, is a component of water and organic compounds. It is the second most abundant element in the human body after sodium. Although the concentration of deuterium in an organism is much lower than that of protium, a wide variety of morphological, biochemical, and physiological changes are known to occur in deuterium-treated cells, including changes in fundamental processes such as cell division or energy metabolism. The mode and degree of changes in cells and tissues, both with an increase and a decrease in the concentration of deuterium, depends primarily on the time of exposure, as well as on the concentration. The reviewed data show that plant and animal cells are sensitive to deuterium content. Any shifts in the D/H balance outside or inside cells promote immediate responses. The review summarizes reported data on the proliferation and apoptosis of normal and neoplastic cells in different modes of deuteration and deuterium depletion in vivo and in vitro. The authors propose their own concept of the effects of changes in deuterium content in the body on cell proliferation and death. The altered rate of proliferation and apoptosis indicate a pivotal role of the hydrogen isotope content in living organisms and suggest the presence of a D/H sensor, which is yet to be detected.

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Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver

Cited by 3 publications

References 71 publications

Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis

Deuterium-Enriched Water Increases the Cytotoxicity of Cyclooxygenase Inhibitors in Hep-G2 Hepatocellular Carcinoma Cells; Involvement of MAPK Pathway and Apoptosis

Deuterium-Depleted Water in Cancer Therapy: A Systematic Review of Clinical and Experimental Trials

Emerging Role of Deuterium/Protium Disbalance in Cell Cycle and Apoptosis

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