Fertility and Prenatal Health program
Research & Studies

Protective effects of hydrogen-rich saline in preeclampsia rat model

 

“The preventive administration of hydrogen significantly attenuated the severity of PE, which might be ascribed to a reduction in inflammation response and oxidative stress. It could be concluded that hydrogen can be an effective antioxidant in the management of PE.”

 

Yang, X., Guo, L., Sun, X., Chen, X., & Tong, X. (2011). Protective effects of hydrogen-rich saline in preeclampsia rat model. Placenta, 32(9), 681-686. doi: 10.1016/j.placenta.2011.06.020

 

Role of oxidative stress in the pathogenesis of preeclampsia

 

“Published evidence of altered biomarkers for the endothelial dysfunction suggests that the initiating event in preeclampsia is the reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium. This review focuses on the role of free radicals in generating the oxidative stress taking antioxidants into consideration which tend to overcome it as well as the role of placenta in preeclamptic pregnancy.”

 

Siddiqui, I. A., Jaleel, A., Tamimi, W., & Kadri, H. M. (2010). Role of oxidative stress in the pathogenesis of preeclampsia. Archives of Gynecology and Obstetrics, 282(5), 469-474. doi: 10.1007/s00404-010-1538-6

 

Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway

 

“H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway.”

 

Chen, H., Xie, K., Han, H., Li, Y., Liu, L., Yang, T., & Yu, Y. (2015). Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway. International Immunopharmacology, 28(1), 643-654. doi: 10.1016/j.intimp.2015.07.034

Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function

 

“H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.”

 

Ishibashi, T., Sakai, T., Sato, B., Hara, K., Hara, Y., Naritomi, Y., . . . Nagao, T. (2014). Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vascular Health and Risk Management, 10(59), 1-7. doi: 10.2147/vhrm.s68844

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

​Impact of oxidative stress on female fertility

 

“Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia), extremes of body weight, alcohol, tobacco, and caffeine intake. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.”

 

Ruder, E. H., Hartman, T. J., & Goldman, M. B. (2009). Impact of oxidative stress on female fertility. Current Opinion in Obstetrics and Gynecology, 21(3), 219-222. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749720/

 

Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells

 

“High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.”

 

Guan, Z., Li, H., Guo, L., & Yang, X. (2015). Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells. Archives of Gynecology and Obstetrics, 292(2), 337-342. doi: 10.1007/s00404-015-3647-8

 

Endothelial dysfunction and preeclampsia: Role of oxidative stress

 

“Risk factors for the development of Preeclampsia include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED).  The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED.”

 

Sã¡nchez-Aranguren, L. C., Prada, C. E., Riaã±O-Medina, C. E., & Lopez, M. (2014). Endothelial dysfunction and preeclampsia: Role of oxidative stress. Frontiers in Physiology, 5(372), 1-11. doi: 10.3389/fphys.2014.00372

 

Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats

 

“Treatment with HRS alleviates vascular dysfunction through abating oxidative stress, restoring baroreflex function, suppressing inflammation, preserving mitochondrial function, and enhancing nitric oxide bioavailability.”

 

Zheng, H., & Yu, Y-S. (2012). Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochemical Pharmacology, 83(9), 1269-1277. doi: 10.1016/j.bcp.2012.01.031

 

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577  

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

“Supplementation with molecular hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistence by helping to stabilize blood sugar, which is a critical aspect of long-term weight loss.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008 

Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress

“Hydrogen saturated saline may improve the insulin resistance and alleviate the symptoms of diabetes mellitus by reducing the oxidative stress and enhancing the anti-oxidant system.”

 

Wang, Q., Zha, X., Kang, Z., Xu, M., Huang, Q., & Zou, D. (2012). Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chinese Medical Journal, 125(9), 1633-1637. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22800834

 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., Li, M., Sang, H., Zhang, L., Li, X., & Qin, S. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized and placebo-controlled trial

 

“H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.”

 

Qin, S. (2015). Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized and placebo-controlled trial. The Journal of Endocrinology and Metabolism, 100(7), 2724-2733. doi: 10.1210/jc.2015-1321

​Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters

 

“Administration of hydrogen-saturated saline decreases plasma LDL cholesterol and apo B levels and improves hyperlipidemia-injured HDL functions, including the capacity of enhancing cellular cholesterol efflux and playing antioxidative properties, in high-fat diet-fed hamsters.”

 

Zong, C., Song, G., Yao, S., Li, L., Yu, Y., Feng, L., . . . Qin, S. (2012). Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet–fed hamsters. Metabolism, 61(6), 794-800. doi: 10.1016/j.metabol.2011.10.014

 

Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice

 

“Hydrogen significantly improved HDL functionality in C57BL/6J mice assessed in two independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells by measuring HDL-induced [(3)H]cholesterol efflux, and (ii) protection against LDL oxidation as a measure of Cu(2+)-induced TBARS formation. These results reveal that administration of hydrogen-saturated saline decreases athero-susceptibility in apoB-containing lipoprotein and aortic atherosclerosis in apoE-/- mice and improves HDL functionality in C57BL/6J mice.”

 

Song, G., Tian, H., Qin, S., Sun, X., Yao, S., Zong, C., . . . Wang, X. (2012). Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice. Atherosclerosis, 221(1), 55-65. doi: 10.1016/j.atherosclerosis.2011.11.043

 

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

 

“H(2) stimulated energy metabolism as measured by oxygen consumption. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome.”

 

Kamimura, N., Nishimaki, K., Ohsawa, I., & Ohta, S. (2011). Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity, 19(7), 1396-1403. doi: 10.1038/oby.2011.6

 

​Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism

 

“In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1αgene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.”

 

Kamimura, N. Ichimaya, H. Iuchi, K. & Ohta, S. (2016). Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1a to enhance fatty acid metabolism. NPJ Aging and Mechanisms of Disease, 2, 1-8. doi: 10.1038/npjamd.2016.8

 

Oxidative stress and epididymal sperm transport, motility and morphological defects

 

“Radical oxidative species (ROS) have an important effect on sperm quality and quantity. High levels of CP can be measured in iOAT patients, indicating that OS could underlie the aetipopathogenesis of the syndrome. OS negatively affects flagellar axonemal structure with subsequent impairment of forward progressive sperm motility. This can put an attention for antioxidants as a therapy for iOAT syndrome and further research to find how to decrease ROS production.”

 

El-Taieb, Moustafa A.a., Ralf Herwig, Essam A. Nada, Joachim Greilberger, and Michael Marberger. (2009). Oxidative stress and epididymal sperm transport, motility and morphological defects. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 144(1), 199-203. doi: 10.1016/j.ejogrb.2009.02.018

 

The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy

 

“Oxidative stress in the male germ line is thought to affect male fertility and impact upon normal embryonic development. Adequately powered, placebo-controlled comprehensive clinical trials are now required to establish a clear role for antioxidants in the prevention of oxidative stress in the male germ line, such that the clinical utility of this form of therapy becomes established once and for all.”

 

Gharagozloo, P., Aitken, J. (2011). The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Oxford Journals, 26(7), 1628-1640. doi: 10.1093/humrep/der132

Long-term treatment of hydrogen-rich saline abates testicular oxidative stress induced by nicotine in mice

 

 “Treatment with hydrogen-rich saline significantly increased both testicular and serum testosterone levels compared to nicotine-treated group. Our results first demonstrated that long-term treatment with hydrogen-rich saline attenuated testicular oxidative level and improved male reproductive function in nicotine-treated mice.”

 

Li, S., Lu, D., Zhang, Y., & Zhang, Y. (2013). Long-term treatment of hydrogen-rich saline abates testicular oxidative stress induced by nicotine in mice. Journal of Assisted Reproduction and Genetics, 31(1), 109-114. doi: 10.1007/s10815-013-0102-2

 

The role of oxidative stress and antioxidants in male fertility

 

“Spermatozoa are particularly vulnerable to the harmful effects of ROS. Oxidative stress affects their activity, damages DNA structure, and accelerates apoptosis, all of which consequently decrease their numbers, hinders motility and development of normal morphology, and impairs function.  In vitro and in vivo that studies demonstrate many antioxidants possess a beneficial effect on fertility and, therefore, their use is recommended as supportive therapy for the treatment of infertility in men.”

 

Walczak–Jedrzejowska, R., Wolski, J. K., & Slowikowska–Hilczer, J. (2013). The role of oxidative stress and antioxidants in male fertility. Central European Journal of Urology, 66(1), 60-67. doi: 10.5173/ceju.2013.01.art19

 

Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice

 

“Recent studies show that molecular hydrogen (dihydrogen, H2) has potential as an effective and safe radioprotective agent through reducing oxidative stress. The aim of this study was to investigate whether H2 is able to protect spermatogenesis and hematopoiesis from radiation-induced injuries. This study demonstrates that treating mice with H2 before ionizing radiation (IR) can increase the spermatid head count and protect seminiferous epithelium from IR. This study suggests that hydrogen-rich saline could partially protect spermatogenesis and hematopoiesis in irradiated mice.”

 

Chuai, Y., Shen, J., Qian, L., Wang, Y., Huang, Y., Gao, F., . . . Cai, J. (2012). Hydrogen-rich saline protects spermatogenesis and hematopoiesis in irradiated BALB/c mice. Medical Science Monitor, 18(3), 89-94. doi: 10.12659/msm.882513

 

Effect of oxidative stress in male infertility

 

“Oxidative stress is involved with many chronic pathological conditions and the current study was designed to evaluate any association that may exist between male infertility and oxidative stress. Infertile male patients show an elevation of oxidative stress markers both in the erythrocytes and in the seminal plasma. Indicating that male infertility might be associated with increased oxidative stress.”

 

Naher, Z., Ali, M., Biswas, S., Mollah, F., Fatima, P., Hossain, M., & Arslan, M. (2013). Effect of oxidative stress in male infertility. Mymensingh Medical Journal, 22(1), 136-142. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/23416821

 

Effect of hydrogen injected subcutaneously on testicular tissues of rats exposed to cigarette smoke

 

“Smoking is one of the most common reasons inducing reactive oxygen species in semen. High concentration of active oxygen will cause decrease of sperm density and viability and induce oxidative injury of sperm DNA which has become the hot spot in male infertility. As a consequence, we concluded that injected subcutaneously exerted protective effects on reproductive system injury of male rats exposed to cigarette smoke through inhibiting oxidative damage.”

 

Chen, S., & Jiang, W. (n.d.). Effect of hydrogen injected subcutaneously on testicular tissues of rats exposed to cigarette smoke. International journal of clinical and experimental medicine, 8(4), 5565-5570. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26131139

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