Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease
Abstract
:1. Introduction
2. Methodology
3. H2 Regulates Oxidative Stress
3.1. History and Progress of Research on Medical Applications of H2
3.2. ROS Production and Scavenging Systems
3.3. “Beneficial” and “Detrimental” Effects of ROS
4. Mitochondrial Involvement in Renal Disease
4.1. Mitochondrial Structure and Function
4.2. Role of ROS in Renal Disease
4.3. Development Status of Diabetic Kidney Disease Therapeutics
5. Effects of H2 on Various Renal Diseases and Vascular Endothelial Function
5.1. Effects on Renal Disease Models in Animals
5.1.1. Ischemia-Reperfusion Injury
5.1.2. Transplantation
5.1.3. Chronic Kidney Disease
5.1.4. Drug-Induced Renal Injury
5.1.5. Renal Stones
5.1.6. Renal Fibrosis
5.1.7. Sepsis-Related Acute Kidney Injury
5.1.8. Others
5.2. Effects on Human Renal Diseases
5.2.1. Peritoneal Dialysis
5.2.2. Hemodialysis
5.3. Effects on Vascular Endothelial Function
6. Mechanism of Action of H2 on Renal Disease
6.1. Improvement in Mitochondrial Function
6.2. Antioxidant Effects
6.3. Anti-Inflammatory Effects
6.4. Regulation of Cell Lethality
6.5. Regulatory Effects of Signal Transduction
7. Therapeutic Potential of H2 for Diabetic Kidney Disease
7.1. Therapeutic Potential of H2 in the Etiology of Diabetic Kidney Disease
7.2. Prospects for H2 as a Therapeutic Substance for Diabetic Kidney Disease
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Koye, D.N.; Magliano, D.J.; Nelson, R.G.; Pavkov, M.E. The global epidemiology of diabetes and kidney disease. Adv. Chronic Kidney Dis. 2018, 25, 121–132. [Google Scholar] [CrossRef]
- Bonner, R.; Albajrami, O.; Hudspeth, J.; Upadhyay, J. Diabetic kidney disease. Prim. Care 2020, 47, 645–649. [Google Scholar] [CrossRef]
- IDF Diabetes Atlas. 2021. Available online: https://diabetesatlas.org/atlas/tenth-edition/ (accessed on 19 June 2023).
- Jha, V.; Garcia-Garcia, G.; Iseki, K.; Naicker, S.; Plattner, B.; Saran, R.; Wang, A.Y.M.; Yang, C.W. Chronic kidney disease: Global dimension and perspectives. Lancet 2013, 382, 260–272. [Google Scholar] [CrossRef]
- Ohsawa, I.; Ishikawa, M.; Takahashi, K.; Watanabe, M.; Nishimaki, K.; Yamagata, K.; Katura, K.I.; Katayama, Y.; Ohta, S. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007, 13, 688–694. [Google Scholar] [CrossRef] [PubMed]
- Nogueira, J.E.; Passaglia, P.; Mota, C.M.D.; Santos, B.M.; Batalhão, M.E.; Carnio, E.C.; Branco, L.G.S. Molecular hydrogen reduces acute exercise-induced inflammatory and oxidative stress status. Free Radic. Biol. Med. 2018, 129, 186–193. [Google Scholar] [CrossRef] [PubMed]
- Wang, D.; Wang, L.; Zhang, Y.; Zhao, Y.; Chen, G. Hydrogen gas inhibits lung cancer progression through targeting SMC3. Biomed. Pharmacother. 2018, 104, 788–797. [Google Scholar] [CrossRef] [PubMed]
- Hirano, S.i.; Ichikawa, Y.; Sato, B.; Takefuji, Y.; Satoh, F. Molecular hydrogen as a potential clinically applicable radioprotective agent. Int. J. Mol. Sci. 2021, 22, 4566. [Google Scholar] [CrossRef]
- Kawamura, T.; Wakabayashi, N.; Shigemura, N.; Huang, C.S.; Masutani, K.; Tanaka, Y.; Nota, K.; Peng, X.; Takahashi, T.; Billiar, T.R.; et al. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. Am. J. Physiol. Lung. Cell Mol. Physiol. 2013, 304, L646–L656. [Google Scholar] [CrossRef] [PubMed]
- Ohta, S. Molecular hydrogen as a novel antioxidant: Overview of the advantages of hydrogen for medical applications. Methods Enzymol. 2015, 555, 289–317. [Google Scholar] [PubMed]
- Jin, Z.; Zhao, P.; Gong, W.; Ding, W.; He, Q. Fe-porphyrin: A redox-related biosensor of hydrogen molecule. Nano Res. 2023, 16, 2020–2025. [Google Scholar] [CrossRef]
- Wei, P.Z.; Szeto, C.C. Mitochondrial dysfunction in diabetic kidney disease. Clin. Chim. Acta 2019, 496, 108–116. [Google Scholar] [CrossRef] [PubMed]
- Su, S.; Ma, Z.; Wu, H.; Xu, Z.; Yi, H. Oxidative stress as a culprit in diabetic kidney disease. Life Sci. 2023, 322, 121661. [Google Scholar] [CrossRef]
- Tanase, D.M.; Gosav, E.M.; Anton, M.I.; Floria, M.; Isac, P.N.S.; Hurjui, L.L.; Tarniceriu, C.C.; Costea, C.F.; Ciocoiu, M.; Rezus, C. Oxidative stress and NRF2/Keap1/ARE pathway in Diabetic kidney disease (DKD): New perspective. Biomolecules 2022, 12, 1227. [Google Scholar] [CrossRef]
- Galvan, D.L.; Mise, K.; Danesh, F.R. Mitochondrial regulation of diabetic kidney disease. Front. Med. 2021, 8, 745279. [Google Scholar] [CrossRef]
- Kanda, H.; Yamawaki, K. Bardoxolone methyl: Drug development for diabetic kidney disease. Clin. Exp. Nephrol. 2020, 24, 857–864. [Google Scholar] [CrossRef]
- Liu, H.; Sridhar, V.S.; Boulet, J.; Dharia, A.; Khan, A.; Lawier, P.R.; Cherney, D.Z.I. Cardiorenal protection with Sglt2 inhibitors in patients with diabetes mellitus: From biomarkers to clinical outcomes in heart failure and diabetic kidney disease. Metab. Clin. Exp. 2022, 126, 154918. [Google Scholar] [CrossRef]
- Yang, S.; Lin, C.; Zhuo, X.; Wang, J.; Rao, S.; Xu, W.; Cheng, Y.; Yang, L. Glucagon-like peptide-1 alleviates diabetic kidney disease through activation of autophagy by regulating Amp-activated protein kinase-mammalian target of rapamycin pathway. Am. J. Phys. Endocrinol. Metab. 2020, 319, E1019–E1030. [Google Scholar] [CrossRef] [PubMed]
- Murphy, M.P.; Smith, R.A. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu. Rev. Pharmacol. Toxicol. 2007, 47, 629–656. [Google Scholar] [CrossRef] [PubMed]
- Suzuki, T.; Yamaguchi, H.; Kikusato, M.; Hashizume, O.; Nagatoshi, S.; Matsuo, A.; Sato, T.; Kudo, T.; Matsuhashi, T.; Murayama, K.; et al. Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage. J. Am. Soc. Nephrol. 2016, 27, 1925–1932. [Google Scholar] [CrossRef] [PubMed]
- Shingu, C.; Koga, H.; Hagiwara, S.; Matsumoto, S.; Goto, K.; Yokoi, I.; Noguchi, T. Hydrogen-rich saline solution attenuates renal ischemia-reperfusion injury. J. Anesth. 2010, 24, 569–574. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Yu, G.; Liu, S.Y.; Li, J.B.; Wang, J.F.; Bo, L.L.; Qian, L.R.; Sun, X.J.; Deng, X.M. Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats. J. Surg. Res. 2011, 167, e339–e344. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Hong, Z.; Liu, H.; Zhou, J.; Cui, L.; Yuan, S.; Chu, X.; Yu, P. Hydrogen-rich saline promotes the recovery of renal function after ischemia/reperfusion injury in rats via anti-apoptosis and anti-inflammation. Front. Pharmacol. 2016, 7, 106. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Zhang, H.; Hu, J.; Gu, Y.; Shen, Z.; Xu, L.; Jia, X.; Zhang, X.; Ding, X. Hydrogen-rich saline alleviates kidney fibrosis following AKI and retains Klotho expression. Front. Pharmacol. 2017, 8, 499. [Google Scholar] [CrossRef] [PubMed]
- Xu, X.; He, X.; Liu, J.; Qin, J.; Ye, J.; Fan, M. Protective effects of hydrogen-rich saline against renal ischemia-reperfusion injury by increased expression of heme oxygenase-1 in aged rats. Int. J. Clin. Exp. Pathol. 2019, 12, 1488–1496. [Google Scholar] [PubMed]
- Cardinal, J.S.; Zhan, J.; Wang, Y.; Sugimoto, R.; Tsung, A.; McCurry, K.R.; Billiar, T.R.; Nakao, A. Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int. 2010, 77, 101–109. [Google Scholar] [CrossRef] [PubMed]
- Abe, T.; Li, X.K.; Yazawa, K.; Hatayama, N.; Xie, L.; Sato, B.; Kakuta, Y.; Tsutahara, K.; Okumi, M.; Tsuda, H.; et al. Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury. Transplantation 2012, 94, 14–21. [Google Scholar] [CrossRef]
- Du, H.; Sheng, M.; Wu, L.; Zhang, Y.; Shi, D.; Weng, Y.; Xu, R.; Yu, W. Hydrogen-rich saline attenuates acute kidney injury after liver transplantation via activating p53-mediated autophagy. Transplantation 2016, 100, 563–570. [Google Scholar] [CrossRef]
- Zhu, W.J.; Nakayama, M.; Mori, T.; Nakayama, K.; Katoh, J.; Murata, Y.; Sato, T.; Kabayama, S.; Ito, S. Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats. Nephrol. Dial. Transplant. 2011, 26, 2112–2118. [Google Scholar] [CrossRef]
- Zhu, W.J.; Nakayama, M.; Mori, T.; Hao, K.; Terawaki, H.; Katoh, J.; Kabayama, S.; Ito, S. Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2-enriched electrolyzed water. Med. Gas. Res. 2013, 3, 26. [Google Scholar] [CrossRef]
- Xin, H.G.; Zhang, B.B.; Wu, Z.Q.; Hang, X.F.; Xu, W.S.; Ni, W.; Zhang, R.Q.; Miao, X.H. Consumption of hydrogen-rich water alleviates renal injury in spontaneous hypertensive rats. Mol. Cell Biochem. 2014, 392, 117–124. [Google Scholar] [CrossRef]
- Nakashima-Kamimura, N.; Mori, T.; Ohsawa, I.; Asoh, S.; Ohta, S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother. Pharmacol. 2009, 64, 753–761. [Google Scholar] [CrossRef] [PubMed]
- Li, F.Y.; Zhu, S.X.; Wang, Z.P.; Wang, H.; Zhao, Y.; Chen, G.P. Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats. Food Chem. Toxicol. 2013, 61, 248–254. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.; Li, C.F.; Ping, N.N.; Sun, Y.Y.; Wang, Z.; Zhao, G.X.; Yuan, S.H.; Zibrila, A.I.; Soong, L.; Liu, J.J. Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway. J. Biochem. Mol. Toxicol. 2020, 34, e22467. [Google Scholar] [CrossRef] [PubMed]
- Peng, Z.; Chen, W.; Wang, L.; Ye, Z.; Gao, S.; Sun, X.; Guo, Z. Inhalation of hydrogen gas ameliorates glyoxylate-induced calcium oxalate deposition and renal oxidative stress in mice. Int. J. Clin. Exp. Pathol. 2015, 8, 2680–2689. [Google Scholar]
- Xu, B.; Zhang, Y.B.; Li, Z.Z.; Yang, M.W.; Wang, S.; Jiang, D.P. Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats. Int. Immunopharmacol. 2013, 17, 447–452. [Google Scholar] [CrossRef]
- Xing, Z.; Pan, W.; Zhang, J.; Xu, X.; Zhang, X.; He, X.; Fan, M. Hydrogen rich water attenuates renal injury and fibrosis by regulation transforming growth factor-β induced Sirt1. Biol. Pharm. Bull. 2017, 40, 610–615. [Google Scholar] [CrossRef]
- Mizutani, A.; Endo, A.A.; Saito, M.; Hara, T.; Nakagawa, M.; Sakuraya, K.; Murano, Y.; Nishizaki, N.; Hirano, D.; Fujinaga, S.; et al. Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction. Pediatr. Res. 2022, 91, 1695–1702. [Google Scholar] [CrossRef]
- Liu, W.; Dong, X.S.; Sun, Y.Q.; Liu, Z. A novel fluid resuscitation protocol: Provide more protection on acute kidney injury during septic shock in rats. Int. J. Clin. Exp. Med. 2014, 15, 919–926. [Google Scholar]
- Yao, W.; Guo, A.; Han, X.; Wu, S.; Chen, C.; Luo, C.; Li, H.; Li, S.; Hei, Z. Aerosol inhalation of a hydrogen-rich solution restored septic renal function. Aging 2019, 11, 12097–12113. [Google Scholar] [CrossRef]
- Guo, S.X.; Fang, Q.; You, C.G.; Jin, Y.Y.; Wang, X.G.; Hu, X.L.; Han, C.M. Effects of hydrogen-rich saline on early acute kidney injury in severely burned rats by suppressing oxidative stress induced apoptosis and inflammation. J. Transl. Med. 2015, 13, 183. [Google Scholar] [CrossRef] [PubMed]
- Shi, Q.; Liao, K.S.; Zhao, K.L.; Wang, W.X.; Zuo, T.; Deng, W.H.; Chen, C.; Yu, J.; Guo, W.Y.; He, X.B.; et al. Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway. Mediators Inflamm. 2015, 2015, 685043. [Google Scholar] [CrossRef] [PubMed]
- Guan, P.; Sun, Z.M.; Luo, L.F.; Zhou, J.; Yang, S.; Zhao, Y.S.; Yu, F.Y.; An, J.R.; Wang, N.; Ji, E.S. Hydrogen protects against chronic intermittent hypoxia induced renal dysfunction by promoting autophagy and alleviating apoptosis. Life Sci. 2019, 225, 46–54. [Google Scholar] [CrossRef] [PubMed]
- Terawaki, H.; Hayashi, Y.; Zhu, W.J.; Matsuyama, Y.; Terada, T.; Kabayama, S.; Watanabe, T.; Era, S.; Sato, B.; Nakayama, M. Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients: A novel approach to suppress oxidative stress in the peritoneal cavity. Med. Gas Res. 2013, 3, 14. [Google Scholar] [CrossRef] [PubMed]
- Nakayama, M.; Nakano, H.; Hamada, H.; Itami, N.; Nakazawa, R.; Ito, S. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: A clinical trial. Nephrol. Dial. Transplant. 2010, 25, 3026–3033. [Google Scholar] [CrossRef]
- Terawaki, H.; Zhu, W.J.; Matsuyama, Y.; Terada, T.; Takahashi, Y.; Sakurai, K.; Kabayama, S.; Miyazaki, M.; Itami, N.; Nakazawa, R. Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients. Hemodial. Int. 2014, 18, 459–466. [Google Scholar] [CrossRef]
- Sokawa, S.; Matsuura, A.; Suga, Y.; Sokawa, Y.; Kojima, T.; Nakamura, H. Reduction of oxidative stress and CRP levels in hemodialysis patients by hydrogen gas inhalation. J. Jpn. Ass. Dial. Physicians 2021, 54, 433–439. [Google Scholar] [CrossRef]
- Hirano, S.i.; Ichikawa, Y.; Sato, B.; Yamamoto, H.; Takefuji, Y.; Satoh, F. Potential therapeutic applications of hydrogen in chronic inflammatory diseases: Possible inhibiting role on mitochondrial stress. Int. J. Mol. Sci. 2021, 22, 2549. [Google Scholar] [CrossRef]
- Hirano, S.i.; Ichikawa, Y.; Sato, B.; Takefuji, Y.; Satoh, F. Molecular hydrogen as a medical gas for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Possible efficacy based on a literature review. Front. Neurosci. 2022, 13, 841310. [Google Scholar]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J. Clin. Epidemiol. 2021, 134, 178–189. [Google Scholar] [CrossRef]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Moher, D. Updating guidance for reporting systematic reviews: Development of the PRISMA 2020 statement. J. Clin. Epidemiol. 2021, 134, 103–112. [Google Scholar] [CrossRef]
- Dole, M.; Wilson, F.R.; Fife, W.P. Hyperbaric hydrogen therapy: A possible treatment for cancer. Science 1975, 190, 152–154. [Google Scholar] [CrossRef]
- Abraini, J.H.; Gardette-Chauffour, M.C.; Martinez, E.; Rostain, J.C.; Lemaire, C. Psychophysiological reactions in humans during an open sea dive to 500 m with a hydrogen-helium-oxygen mixture. J. Appl. Physiol. 1994, 76, 1113–1118. [Google Scholar] [CrossRef]
- Gharib, B.; Hanna, S.; Abdallahi, O.M.; Lepidi, H.; Gardette, B.; De Reggi, M. Anti-inflammatory properties of molecular hydrogen: Investigation on parasite-induced liver inflammation. Comptes R. Acad. Sci. III 2001, 324, 719–724. [Google Scholar] [CrossRef]
- Yanagihara, T.; Arai, K.; Miyamae, K.; Sato, B.; Shudo, T.; Yamada, M.; Aoyama, M. Electrolyzed hydrogen-saturated water for drinking use elicits an antioxidative effect: A feeding test with rats. Biosci. Biotechnol. Biochem. 2005, 69, 1985–1987. [Google Scholar] [CrossRef] [PubMed]
- Ohta, S. Molecular hydrogen may activate the transcription factor Nrf2 to alleviate oxidative stress through the hydrogen-targeted porphyrin. Aging Pathobiol. Ther. 2023, 5, 25–32. [Google Scholar] [CrossRef]
- Hirano, S.I.; Yamamoto, H.; Ichikawa, Y.; Sato, B.; Takefuji, Y. Molecular hydrogen as a novel antitumor agent: Possible mechanisms underlying gene expression. Int. J. Mol. Sci. 2021, 22, 8724. [Google Scholar] [CrossRef] [PubMed]
- Ohta, S. Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacol. Ther. 2014, 144, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Halliwell, B.; Gutteridge, J.M.C. Biologically relevant metal ion-dependent hydroxyl radical generation. FEBS Lett. 1992, 307, 108–112. [Google Scholar] [CrossRef]
- Setsukinai, K.I.; Urano, Y.; Kakinuma, K.; Majima, H.J.; Nagano, T. Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J. Biol. Chem. 2003, 278, 3170–3175. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Takahara, T.; Que, W.; Fujino, M.; Guo, W.Z.; Hirano, S.I.; Ye, L.P.; Li, X.K. Hydrogen-rich water protects liver injury in nonalcoholic steatohepatitis though HO-1 enhancement via IL-10 and Sirt 1 signaling. Am. J. Physiol. Gastrointest. Liver Physiol. 2021, 320, G450–G463. [Google Scholar] [CrossRef] [PubMed]
- Levine, A.J.; Oren, M. The first 30 years of p53: Growing ever more complex. Nat. Rev. Cancer 2009, 9, 749–758. [Google Scholar] [CrossRef]
- Ohsawa, I. Biological responses to hydrogen molecule and its preventive effects on inflammatory disease. Curr. Pharm. Des. 2021, 27, 659–666. [Google Scholar] [CrossRef] [PubMed]
- Klein, E.A.; Thompson, I.M.; Tangen, C.M.; Growley, J.J.; Lucia, M.S.; Goodman, P.J.; Minasian, L.M.; Ford, L.G.; Parnes, H.L.; Gaziano, J.M.; et al. Vitamin E and the risk of prostate cancer. The selenium and vitamin E cancer prevention trial (Select). J. Am. Med. Assoc. 2011, 306, 1549–1556. [Google Scholar] [CrossRef] [PubMed]
- Chandel, N.S.; Tuveson, D.A. The promise and perils of antioxidants for cancer patients. N. Engl. J. Med. 2014, 371, 177–178. [Google Scholar] [CrossRef] [PubMed]
- Sayin, V.I.; Ibrahim, M.X.; Larsson, E.; Nilsson, J.A.; Lindahl, P.; Bergo, M.O. Antioxidants accelerate lung progression in mice. Sci. Transl. Med. 2014, 6, 221ra15. [Google Scholar] [CrossRef]
- DeNicola, G.M.; Karreth, F.A.; Humpton, T.J.; Gopinathan, A.; Wei, C.; Frese, K.; Mangal, D.; Yu, K.H.; Yeo, C.J.; Calhoun, E.S.; et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011, 475, 106–109. [Google Scholar] [CrossRef] [PubMed]
- Schafer, Z.T.; Grassian, A.R.; Song, L.; Jiang, Z.; Gerhart-Hines, Z.; Irie, H.Y.; Gao, S.; Puigserver, P.; Brugge, J.S. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009, 461, 109–113. [Google Scholar] [CrossRef]
- Kawai, D.; Takaki, A.; Nakatsuka, A.; Wada, J.; Tamaki, N.; Yasunaka, T.; Koike, K.; Tsuzaki, R.; Matsumoto, K.; Miyake, Y.; et al. Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology 2012, 56, 912–921. [Google Scholar] [CrossRef]
- Halliwell, B.; Gutteridge, J.M.C. Chapter 10. Reactive Species in Disease: Friends or Foes? Free Radicals in Biology and Medicine, 5th ed.; Oxford University Press: Oxford, UK, 2015; pp. 511–638. [Google Scholar]
- Rotariu, D.; Babes, E.E.; Tit, D.M.; Moisi, M.; Bustea, C.; Stoicescu, M.; Radu, A.F.; Vesa, C.M.; Behl, T.; Bungau, A.F.; et al. Oxidative stress—Complex pathological issues concerning the hallmark of cardiovascular and metabolic disorders. Biomed. Pharmacother. 2022, 152, 113238. [Google Scholar] [CrossRef]
- Zerbes, R.M.; van der Klei, I.J.; Veenhuis, M.; Pfanner, M.; van der Laan, M.; Bohnert, M. Mitofilin complexes: Conserved organizers of mitochondrial membrane architecture. Biol. Chem. 2012, 393, 1247. [Google Scholar] [CrossRef]
- Roger, A.G.; Muñoz-Gómez, S.A.; Kamikawa, R. The origin and diversification of mitochondria. Curr. Biol. 2017, 27, R1177–R1192. [Google Scholar] [CrossRef]
- Gorman, G.S.; Chinnery, P.F.; DiMauro, S.; Hirano, M.; Koga, Y.; McFarlamd, R.; Suomalainen, A.; Thorburn, D.R.; Zeviani, M.; Turnbull, D.M. Mitochondrial diseases. Nat. Rev. Dis. Primers 2016, 2, 16080. [Google Scholar] [CrossRef] [PubMed]
- Emma, F.; Montini, G.; Parikh, S.M.; Salviati, L. Mitochondrial dysfunction in inherited renal disease and acute kidney injury. Nat. Rev. Nephrol. 2016, 12, 267. [Google Scholar] [CrossRef] [PubMed]
- Schapira, A.H. Mitochondrial disorders. Curr. Opin. Neurol. 2000, 13, 527–532. [Google Scholar] [CrossRef] [PubMed]
- Rahman, J.; Rahman, S. Mitochondrial medicine in the omics era. Lancet 2018, 391, 2560. [Google Scholar] [CrossRef] [PubMed]
- Guerrero-Molina, M.P.; Morales–Conejo, M.; Delmiro, A.; Morán, M.; Domínguez-González, C.; Arranz-Canales, E.; Ramos-González, A.; Arenas, J.; Martín, M.A.; de la Aleja, J.G. High-dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome. Eur. J. Neurol. 2023, 30, 538–547. [Google Scholar] [CrossRef]
- Archer, S.L. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N. Engl. J. Med. 2013, 369, 2236. [Google Scholar] [CrossRef]
- Bhargava, P.; Schnellmann, R.G. Mitochondria energetics in the kidney. Nat. Rev. Nephrol. 2017, 13, 629–646. [Google Scholar] [CrossRef]
- Abe, Y.; Sakairi, T.; Kajiyama, H.; Shrivastav, S.; Beeson, C.; Kopp, J.B. Bioenergetic characterization of mouse podocytes. Am. J. Physiol. Cell Physiol. 2010, 299, C464–C476. [Google Scholar] [CrossRef]
- Ozawa, S.; Ueda, S.; Imamura, H.; Mori, K.; Asanuma, K.; Yanagita, M.; Nakagawa, T. Glycolysis, but not mitochondria, responsible for intracellular ATP distribution in cortical area of podocytes. Sci. Rep. 2015, 5, 18575. [Google Scholar] [CrossRef]
- Imasawa, T.; Rossignol, R. Podocytes energy metabolism and glomerular disease. Int. J. Biochem. Cell Biol. 2013, 45, 2109–2118. [Google Scholar] [CrossRef]
- Fink, B.D.; Herlein, J.A.; O’Malley, Y.; Sivitz, W.I. Endothelial cell and platelet bioenergetics: Effect of glucose and nutrient composition. PLoS ONE 2012, 7, e39430. [Google Scholar] [CrossRef]
- Czajka, A.; Malik, A.N. Hyperglycemia induced damage to mitochondria respiration in renal mesangial and tubular cells: Implication for diabetic nephropathy. Redox. Biol. 2016, 10, 100–107. [Google Scholar] [CrossRef] [PubMed]
- Dugan, L.L.; You, Y.H.; Ali, S.S.; Diamond-Stanic, M.; Miyamoto, S.; DeCleves, A.E.; Andreyev, A.; Quach, T.; Ly, S.; Shekhtman, G.; et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J. Clin. Investig. 2013, 123, 4888–4899. [Google Scholar] [CrossRef]
- Forbes, J.M.; Thorburn, D.R. Mitochondrial dysfunction in diabetic kidney disease. Nat. Rev. Nephrol. 2018, 14, 291–312. [Google Scholar] [CrossRef] [PubMed]
- Nishikawa, T.; Edelstein, D.; Du, X.L.; Yamagishi, S.; Matsumura, T.; Kaneda, Y.; Yorek, M.A.; Beebe, D.; Oates, P.J.; Hammes, H.P.; et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000, 404, 787–790. [Google Scholar] [CrossRef] [PubMed]
- Brownlee, M. The Pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005, 54, 1615–1625. [Google Scholar] [CrossRef] [PubMed]
- Sagoo, M.K.; Gnudi, L. Diabetic nephropathy: Is there a role for oxidative stress? Free Radic. Biol. Med. 2018, 116, 50–63. [Google Scholar] [CrossRef] [PubMed]
- Zhan, M.; Brooks, C.; Liu, F.; Sun, L.; Dong, Z. Mitochondrial dynamics: Regulatory mechanisms and emerging role in renal pathophysiology. Kidney Int. 2013, 83, 568–581. [Google Scholar] [CrossRef]
- Sharma, K. Mitochondrial hormesis and diabetic complications. Diabetes 2015, 64, 663–672. [Google Scholar] [CrossRef] [PubMed]
- Coughlan, M.T.; Sharma, K. Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease. Kidney Int. 2016, 90, 272–279. [Google Scholar] [CrossRef] [PubMed]
- Hong, D.S.; Kurzrock, R.; Supko, J.G.; He, X.; Naing, A.; Wheler, J.; Lawrence, D.; Eder, J.P.; Meyer, C.J.; Ferguson, D.A.; et al. A phase I first-in-human trial of bardoxolone methyl in patients advanced solid tumors and lymphomas. Clin. Cancer Res. 2012, 18, 3396–3406. [Google Scholar] [CrossRef] [PubMed]
- Nangaku, M.; Takama, H.; Ichikawa, K.; Mukai, K.; Kojima, M.; Suzuki, Y.; Watada, H.; Wada, T.; Ueki, K.; Narita, I.; et al. Randomized, double-blind, placebo-controlled phase 3 study of bardoxolone methyl in patients with diabetic kidney disease: Design and baseline characteristics of Ayame study. Nephrol. Dial. Transplant. 2023, 38, 1204–1216. [Google Scholar] [CrossRef] [PubMed]
- A Phase III Double-Blind Placebo-Controlled Trial of Bardoxolone Methyl (AYAME Trial) in Japan. News Releases from Kyowa Kirin Co., Ltd. Available online: https://www.kyowakirin.co.jp/pressroom/news_releases/2023/20230510_01.html (accessed on 19 July 2023).
- Huang, J.; Huang, K.; Lan, T.; Xie, X.; Shen, X.; Liu, P.; Huang, H. Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway. Mol. Cell. Endocrinol. 2013, 365, 231–240. [Google Scholar] [CrossRef] [PubMed]
- Shang, G.; Tang, X.; Gao, P.; Guo, F.; Liu, H.; Zhao, Z.; Chen, Q.; Jiang, T.; Zhang, N.; Li, H. Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 Beta/Fyn/Nrf2 signaling pathway. J. Nutr. Biochem. 2015, 26, 596–606. [Google Scholar] [CrossRef] [PubMed]
- El-Bassossy, H.M.; Fahmy, A.; Badawy, D. Cinnamaldehyde Protects from the Hypertension Associated with Diabetes. Food Chem. Toxicol. 2011, 49, 3007–3012. [Google Scholar] [CrossRef]
- Sattarinezhad, A.; Roozbeh, J.; Shirazi Yeganeh, B.; Omrani, G.R.; Shams, M. Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial. Diabetes Metab. 2019, 45, 53–59. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Z.; Tan, Z.; Meng, Z.; Li, X. Curative effects of valsartan alone or combined with alpha-lipoic acid on inflammatory cytokines and renal function in early-stage diabetic kidney disease. J. Coll. Phys. Surg. Pak. 2019, 29, 1009–1011. [Google Scholar] [CrossRef] [PubMed]
- Sun, J.; Zhu, H.; Wang, X.; Cao, Q.; Li, Z.; Hung, H. CoQ10 ameliorates mitochondrial dysfunction in diabetic nephropathy through mitophagy. J. Endocrinol. 2019, 240, 445–465. [Google Scholar] [CrossRef]
- Szeto, H.H. Pharmacologic approaches to improve mitochondrial function in AKI and CKD. J. Am. Soc. Nephrol. 2017, 28, 2856–2865. [Google Scholar] [CrossRef]
- Ducasa, G.M.; Mitrofanova, A.; Mallela, S.K.; Liu, X.; Molina, J.; Sloan, A.; Pedigo, C.E.; Ge, M.; Santos, J.V.; Hernandez, Y.; et al. ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes. J. Clin. Investig. 2019, 129, 3387–3400. [Google Scholar] [CrossRef] [PubMed]
- Matsuhashi, T.; Sato, T.; Kanno, S.I.; Suzuki, T.; Matsuo, A.; Oba, Y.; Kikusato, M.; Ogasawara, E.; Kudo, T.; Suzuki, K.; et al. Mitochonic acid 5 (MA-5) facilitates ATP synthase oligomerization and cell survival in various mitochondrial disease. EBioMedicine 2017, 20, 27–38. [Google Scholar] [CrossRef] [PubMed]
- Clinical Trial of MA-5, a Treatment for Mitochondrial Disease. Press Releases from Tohoku University. Available online: https://www.tohoku.ac.jp/japanese/2021/12/press20211206-02-ma5.html (accessed on 24 July 2023).
- Tit, D.M.; Bungau, S.G. Antioxidant activity of essential oils. Antioxidant 2023, 12, 383. [Google Scholar] [CrossRef] [PubMed]
- Sharma, V.; Gautam, D.N.S.; Radu, A.F.; Behl, T.; Bungau, S.G.; Vesa, C.M. Reviewing the Traditional/Modern Uses, Phytochemistry, Essential Oils/Extracts and Pharmacology of Embelia ribes Burm. Antioxidants 2022, 11, 1359. [Google Scholar] [CrossRef] [PubMed]
- Abdel-Daim, M.M.; Abo-El-Sooud, K.; Aleya, L.; Bungǎu, S.G.; Najda, A.; Saluja, R. Alleviation of drugs and chemicals toxicity: Biomedical value of antioxidants. Oxid. Med. Cell Longev. 2018, 2018, 6276438. [Google Scholar] [CrossRef] [PubMed]
- Arellano-Buendía, A.S.; Castañeda-Lara, L.G.; Loredo-Mendoza, M.L.; García-Arroyo, F.E.; Rojas-Morales, P.; Argüello-García, R.; Juárez-Rojas, J.G.; Tapia, E.; Pedraza-Chaverri, J.; Sánchez-Lozada, L.G.; et al. Effects of allicin on pathophysiological mechanisms during the progression of nephropathy associated to diabetes. Antioxidants 2020, 9, 1134. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Xiao, Y.; Gao, H.; Li, B.; Xu, L.; Cheng, M.; Jiang, B.; Ma, Y. Grape seed proanthocyanidins ameliorate diabetic nephropathy via modulation of levels of AGE, RAGE and CTGF. Nephron Exp. Nephrol. 2009, 111, e31–e41. [Google Scholar] [CrossRef]
- Zhang, X.; Zheng, Y.; Wang, Z.; Gan, J.; Yu, B.; Lu, B.; Jiang, X. Melatonin as a therapeutic agent for alleviating endothelial dysfunction in cardiovascular diseases: Emphasis on oxidative stress. Biomed. Pharmacother. 2023, 167, 115475. [Google Scholar] [CrossRef]
- Jiang, J.; Yu, P.; Qian, D.H.; Qin, Z.X.; Sun, X.J.; Yu, J.; Huang, L. Hydrogen-rich medium suppresses the generation of reactive oxygen species, elevates the Bcl-2/Bax ratio and inhibits advanced glycation end product-induced apoptosis. Int. J. Mol. Med. 2013, 31, 1381–1387. [Google Scholar] [CrossRef]
- Ohsawa, I.; Nishimaki, K.; Yamagata, K.; Ishikawa, M.; Ohta, S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem. Biophys. Res. Commun. 2008, 377, 1195–1198. [Google Scholar] [CrossRef]
- Truong, S.K.; Katoh, T.; Mimuro, T.; Sato, T.; Kobayashi, K.; Nakajima, Y. Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke. Shock 2021, 56, 593–600. [Google Scholar] [CrossRef]
- Song, G.; Li, M.; Sang, H.; Zhang, L.; Li, X.; Yao, S.; Yu, Y.; Zong, C.; Xue, Y.; Qin, S. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. J. Lipid Res. 2013, 54, 1884–1893. [Google Scholar] [CrossRef] [PubMed]
- Sakai, T.; Sato, B.; Hara, K.; Hara, Y.; Naritomi, Y.; Koyanagi, S.; Hara, H.; Nagao, T.; Ishibashi, T. Consumption of water containing 3.5 mg of dissolved hydrogen could improve vascular endothelial function. Vasc. Health Risk Manag. 2014, 10, 591–597. [Google Scholar]
- Ishibashi, T.; Kawamoto, K.; Matsuno, K.; Ishihara, G.; Baba, T.; Komori, N. Peripheral endothelial function can be improved by daily consumption of water containing over 7 ppm of dissolved hydrogen: A randomized controlled trial. PLoS ONE 2020, 15, e0233484. [Google Scholar] [CrossRef] [PubMed]
- Mason, D.R.; Beck, P.L.; Muruve, D.A. Nucleotide-binding oligomerization domain-like receptors and inflammasomes in the pathogenesis of non-microbial inflammation and disease. J. Innate. Immun. 2012, 4, 16–30. [Google Scholar] [CrossRef] [PubMed]
- Wallet, S.M.; Puri, V.; Gibson, F.C. Linkage of infection to adverse systemic complication: Periodontal disease, toll-like receptors, and other pattern recognition systems. Vaccines 2018, 6, 21. [Google Scholar] [CrossRef]
- Man, S.M.; Kanneganti, T.D. Regulation of inflammasome activation. Immunol. Rev. 2015, 265, 6–21. [Google Scholar] [CrossRef] [PubMed]
- Elliott, E.I.; Sutterwala, F.S. Initiation and perpetuation of NLRP3 inflammasome activation and assembly. Immunol. Rev. 2015, 265, 35–52. [Google Scholar] [CrossRef]
- Juliana, C.; Fernandes-Alnemri, T.; Kang, S.; Farias, A.; Qin, F.; Alnemri, E.S. Non -transcriptional priming and deubiquitination regulate NLRP3 inflammasome activation. J. Biol. Chem. 2012, 287, 36617–36622. [Google Scholar] [CrossRef]
- Matsushita, M.; Nakamura, T.; Morizumi, H.; Miki, H.; Takekawa, M. Stress-responsive MTK1 SAPKKK serves as a redox sensor that mediates delayed and sustained activation of SAPKs by oxidative stress. Sci. Adv. 2020, 6, eaay9778. [Google Scholar] [CrossRef]
- Pueyo, M.E.; Gonzalez, W.; Nicoletti, A.; Savoie, F.; Arnal, J.F.; Michel, J.B. Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via NF-kB activation induced by intracellular oxidative stress. Arterioscler. Thromb. Vasc. Biol. 2000, 20, 645–651. [Google Scholar] [CrossRef]
- Higashi, Y. Roles of oxidative stress and inflammation in vascular endothelial dysfunction-related disease. Antioxidants 2022, 11, 1958. [Google Scholar] [CrossRef] [PubMed]
- Nishi, Y.; Satoh, M.; Nagasu, H.; Kadoya, H.; Ihoriya, C.; Kidokoro, K.; Sasaki, T.; Kashihara, N. Selective estrogen receptor modulation attenuates proteinuria-induced renal tubular damage by modulating mitochondrial oxidative status. Kidney Int. 2013, 83, 662–673. [Google Scholar] [CrossRef]
- Kadoya, H.; Satoh, M.; Sasaki, T.; Taniguchi, S.; Takahashi, M.; Kashihara, N. Aldosterone is a critical danger signal for inflammasome activation in development of renal fibrosis in mice. FASEB J. 2015, 29, 3899–3910. [Google Scholar] [CrossRef]
- Shahzad, K.; Bock, F.; Al-Dabet, M.M.; Gadi, I.; Kohli, S.; Nazir, S.; Ghosh, S.; Ranjan, S.; Wang, H.; Madhusudhan, T.; et al. Caspase-1, but not caspase-3, promotes diabetic nephropathy. J. Am. Soc. Nephrol. 2016, 27, 2270–2275. [Google Scholar] [CrossRef] [PubMed]
- Ren, J.D.; Wu, X.B.; Jiang, R.; Hao, D.P.; Liu, Y. Molecular hydrogen inhibits lipopolysaccharide-triggered NLRP3 inflammasome activation in macrophages by targeting the mitochondrial reactive oxygen species. Biochim. Biophys. Acta 2016, 1863, 50–55. [Google Scholar] [CrossRef]
- Yang, L.; Guo, Y.; Fan, X.; Chen, Y.; Yang, B.; Liu, K.X.; Zhou, J. Amelioration of coagulation disorders and inflammation by hydrogen-rich solution reduces intestinal ischemia/reperfusion injury in rats through NF-kB/NLRP3 pathway. Mediat. Inflamm. 2020, 2020, 4359305. [Google Scholar] [CrossRef] [PubMed]
- Zou, R.; Wang, M.H.; Chen, Y.; Fan, X.; Yang, B.; Du, J.; Wang, X.B.; Liu, K.X.; Zhou, J. Hydrogen-rich saline attenuates acute lung injury induced by limb ischemia/reperfusion via down-regulating chemerin and NLRP3 in rats. Shock 2018, 52, 134–141. [Google Scholar] [CrossRef] [PubMed]
- Chen, H.; Zhou, C.; Xie, K.; Meng, X.; Wang, Y.; Yu, Y. Hydrogen-rich saline alleviated the hyperpathia and microglia activation via autophagy mediated inflammasome inactivation in neuropathic pain rats. Neuroscience 2019, 421, 17–30. [Google Scholar] [CrossRef]
- Shao, A.; Wu, H.; Hong, Y.; Tu, S.; Sun, X.; Wu, Q.; Zhao, Q.; Zhang, J.; Sheng, J. Hydrogen-rich saline attenuated subarachnoid hemorrhage-induced early brain injury in rats by suppressing inflammatory response: Possible involvement of NF-kB pathway and NLRP3 inflammasome. Mol. Neurobiol. 2016, 53, 3462–3476. [Google Scholar] [CrossRef]
- Zhuang, K.; Zuo, Y.C.; Scherchan, P.; Wang, J.K.; Yan, X.X.; Liu, F. Hydrogen inhalation attenuates oxidative stress related endothelial cells injury after subarachnoid hemorrhage in rats. Front. Neurosci. 2020, 13, 1441. [Google Scholar] [CrossRef] [PubMed]
- Jiao, Y.; Yu, Y.; Li, B.; Gu, X.; Xie, K.; Wang, G.; Yu, Y. Protective effects of hydrogen-rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP-sensitive potassium channel channels in rats. Mol. Med. Rep. 2020, 21, 282–290. [Google Scholar] [CrossRef] [PubMed]
- Hirano, S.I.; Ichikawa, Y.; Sato, B.; Satoh, F.; Takefuji, Y. Hydrogen is promising for medical applications. Clean. Technol. 2020, 2, 529–541. [Google Scholar] [CrossRef]
- Liu, C.; Kurokawa, R.; Fujino, M.; Hirano, S.I.; Sato, B.; Li, X.K. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes. Sci. Rep. 2014, 4, 5485. [Google Scholar] [CrossRef] [PubMed]
Species | Type of H2 | Effects of H2 | Ref. | |
---|---|---|---|---|
Diseases | Changes in Biomarkers | |||
Rats | HRS | AKI | Swelling of Mt.↓, BUN↓, Cr↓, 8-OHdG↓ | [21] |
Rats | HRS | I/R injury | BUN↓, Cr↓, MDA↓, 8-OHdG↓, TNF-α↓, IL-1β↓, IL-6↓, MPO↓, SOD↑, CAT↑ | [22] |
Rats | HRS | I/R injury | Tissue injury↓, BUN↓, Cr↓, Bcl-2↓, Caspase-3, -8, and -9↓, IL-6↓, TNF-α↓, Bax↑ | [23] |
Mice | HRS | AKI | Tissue injury↓, BUN↓, Cr↓, Klotho↑, Beclin-1↑, LC3- II↑ | [24] |
Rats | HRS | I/R injury | BUN↓, Cr↓, MDA↓, 8-OHdG↓, HO-1↑, SOD↑ | [25] |
Rats | HRW | Renal Transplantation | Overall survival↑, BUN↓, Cr↓, Urinary protein↓, MDA↓, TNF-α↓, IL-6↓, MAPK↓ | [26] |
Rats | HRUW | Renal Transplantation | Overall survival↑, MDA↓, 8-OHdG↓, TUNEL-stained cells↓, ED-1-positive cells↓, Cr↓, Urinary protein↓ | [27] |
Rats | HRW | AKI | BUN↓, Cr↓, MDA↓, SOD↑, Caspase-3↓, Cytochrome C↓, Beclin-1↑, LC3- II↑ | [28] |
Rats | EW | CKD | MCP-1↓, Methylglyoxal↓, BUN↓, Nitrotyrosine staining↓ | [29] |
Rats | EW | CKD | Age-related histological changes↓, albuminuria↓, cardiac remodeling↓, MDA↓, nitrotyrosine staining↓ | [30] |
Rats | HRW | CKD | BUN↓, Cr↓, ROS↓, SOD↑, GPX↑, CAT↑, NADPH oxidase↓, TNF-α↓, IL-6↓, IL-1β↓ | [31] |
Mice | HRW/H2 gas | Cisplatin-induced injury | Histological injury ↓, BUN↓, Cr↓ | [32] |
Rats | HRW | Fe-NTA-induced injury | Cr↓, BUN↓, MDA↓, ONOO−↓, NADPH oxidase↓, CAT↑, mtROS↓, NF-κB↓, IL-6↓, MCP-1↓, VEGF↓, STAT3↓ | [33] |
Rats | HRW | Cyclosporin A-induced injury | ROS↓, MDA↓, Keap1↓, Nrf-2↑, HO-1↑ | [34] |
Mice | H2 gas | Renal stones | MDA↓, 8-OHdG↓, SOD↑, GSH↑, CAT↑, MCP-1↓, IL-10↑ | [35] |
Rats | HRS | Renal fibrosis | Injury score↓, apoptosis index↓, stromal fibrosis↓, MDA↓, SOD↑ | [36] |
Mice | HRW | Renal fibrosis | Cr↓, BUN↓, fibrosis↓, EMT↓, Sirt1↑ | [37] |
Rats | HRW | Renal fibrosis | Fibrosis↓, TGF-β1-positive cells↓, Klotho↑ | [38] |
Rats | H2 gas | Sepsis-related AKI | BUN↓, Cr↓, MDA↓, TNF-α↓, IL-6↓ | [39] |
Mice | HRS | Sepsis-related AKI | IL-4 ↑, IL-13↑, IL-10↑, TGF-β↑ | [40] |
Rats | HRS | Burn-induced AKI | BUN↓, Cr↓, tubular apoptosis↓, inflammation↓, MAPK↓, NF-κB↓ | [41] |
Rats | HRS | AKI | NF-κB↓, ROS↓ | [42] |
Rats | H2 gas | Hypoxia-induced injury | Renal function↑, histological damage↓, oxidative stress↓, apoptosis↓, MAPK↓ | [43] |
Humans | HED | PD | Reduced albumin↑, oxidized albumin↓ | [44] |
Humans | HED | HD | SBP↓, MCP-1↓, MPO↓ | [45] |
Humans | HED | HD | Oxidized albumin↓ | [46] |
Humans | H2 gas | HD | d-ROMs↓, CRP↓ | [47] |
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Hirano, S.-i.; Ichikawa, Y.; Sato, B.; Takefuji, Y.; Satoh, F. Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease. Biomedicines 2023, 11, 2817. https://doi.org/10.3390/biomedicines11102817
Hirano S-i, Ichikawa Y, Sato B, Takefuji Y, Satoh F. Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease. Biomedicines. 2023; 11(10):2817. https://doi.org/10.3390/biomedicines11102817
Chicago/Turabian StyleHirano, Shin-ichi, Yusuke Ichikawa, Bunpei Sato, Yoshiyasu Takefuji, and Fumitake Satoh. 2023. "Clinical Use and Treatment Mechanism of Molecular Hydrogen in the Treatment of Various Kidney Diseases including Diabetic Kidney Disease" Biomedicines 11, no. 10: 2817. https://doi.org/10.3390/biomedicines11102817