Reactive Oxygen Species in Cystic Kidney Disease
Abstract
:1. Introduction
2. Pathophysiology
3. Clinical Outcomes
4. Treatment and Therapeutic Interventions
5. Future Directions
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Goksu, S.Y.; Leslie, S.W.; Khattar, D. Renal Cystic Disease. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK554504/ (accessed on 18 June 2024).
- Raina, R.; Chakraborty, R.; Sethi, S.K.; Kumar, D.; Gibson, K.; Bergmann, C. Diagnosis and Management of Renal Cystic Disease of the Newborn: Core Curriculum 2021. Am. J. Kidney Dis. 2021, 78, 125–141. [Google Scholar] [CrossRef] [PubMed]
- Müller, R.-U.; Benzing, T. Cystic Kidney Diseases from the Adult Nephrologist’s Point of View. Front. Pediatr. 2018, 6, 65. [Google Scholar] [CrossRef] [PubMed]
- Gyurászová, M.; Gurecká, R.; Bábíčková, J.; Tóthová, Ľ. Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers. Oxidative Med. Cell. Longev. 2020, 2020, 5478708. [Google Scholar] [CrossRef] [PubMed]
- Andries, A.; Daenen, K.; Jouret, F.; Bammens, B.; Mekahli, D.; Van Schepdael, A. Oxidative stress in autosomal dominant polycystic kidney disease: Player and/or early predictor for disease progression? Pediatr. Nephrol. 2018, 34, 993–1008. [Google Scholar] [CrossRef] [PubMed]
- Bremmer, M.S.; Halvorson, C.R.; Jacobs, S.C. Polycystic kidney disease: Inheritance, pathophysiology, prognosis, and treatment. Int. J. Nephrol. Renov. Dis. 2010, 3, 69–83. [Google Scholar] [CrossRef] [PubMed]
- Terryn, S.; Ho, A.; Beauwens, R.; Devuyst, O. Fluid transport and cystogenesis in autosomal dominant polycystic kidney disease. Biochim. Biophys. Acta Mol. Basis Dis. 2011, 1812, 1314–1321. [Google Scholar] [CrossRef]
- Nauli, S.M.; Alenghat, F.J.; Luo, Y.; Williams, E.; Vassilev, P.; Li, X.; Elia, A.E.H.; Lu, W.; Brown, E.M.; Quinn, S.J.; et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 2003, 33, 129–137. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Li, L.X.; Zhou, J.X.; Harris, P.C.; Calvet, J.P.; Li, X. RNA helicase p68 inhibits the transcription and post-transcription of Pkd1 in ADPKD. Theranostics 2020, 10, 8281–8297. [Google Scholar] [CrossRef] [PubMed]
- Nakashima, M.; Suga, N.; Ikeda, Y.; Yoshikawa, S.; Matsuda, S. Inspiring Tactics with the Improvement of Mitophagy and Redox Balance for the Development of Innovative Treatment against Polycystic Kidney Disease. Biomolecules 2024, 14, 207. [Google Scholar] [CrossRef] [PubMed]
- Mahboob, M.; Rout, P.; Leslie, S.W.; Bokhari, S.R.A. Autosomal Dominant Polycystic Kidney Disease. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2024. Available online: https://www.ncbi.nlm.nih.gov/books/NBK532934/ (accessed on 19 June 2024).
- Torres, V.E. Vasopressin Antagonists in Polycystic Kidney Disease. Semin. Nephrol. 2008, 28, 306–317. [Google Scholar] [CrossRef] [PubMed]
- Kahveci, A.S.; Barnatan, T.T.; Kahveci, A.; Adrian, A.E.; Arroyo, J.; Eirin, A.; Harris, P.C.; Lerman, A.; Lerman, L.O.; Torres, V.E.; et al. Oxidative Stress and Mitochondrial Abnormalities Contribute to Decreased Endothelial Nitric Oxide Synthase Expression and Renal Disease Progression in Early Experimental Polycystic Kidney Disease. Int. J. Mol. Sci. 2020, 21, 1994. [Google Scholar] [CrossRef] [PubMed]
- Korsmo, H.W.; Ekperikpe, U.S.; Daehn, I.S. Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease. Antioxidants 2024, 13, 712. [Google Scholar] [CrossRef] [PubMed]
- Redza-Dutordoir, M.; Averill-Bates, D.A. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim. Biophys. Acta 2016, 1863, 2977–2992. [Google Scholar] [CrossRef]
- Menon, V.; Rudym, D.; Chandra, P.; Miskulin, D.; Perrone, R.; Sarnak, M. Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease. Clin. J. Am. Soc. Nephrol. 2011, 6, 7–13. [Google Scholar] [CrossRef] [PubMed]
- Ecder, T.; Schrier, R.W. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat. Rev. Nephrol. 2009, 5, 221–228. [Google Scholar] [CrossRef] [PubMed]
- Grantham, J.J.; Mulamalla, S.; Swenson-Fields, K.I. Why kidneys fail in autosomal dominant polycystic kidney disease. Nat. Rev. Nephrol. 2011, 7, 556–566. [Google Scholar] [CrossRef] [PubMed]
- Helal, I. Treatment and Management of Autosomal Dominant Polycystic Kidney Disease. In Polycystic Kidney Disease; Li, X., Ed.; Codon Publications: Brisbane, Australia, 2015; Chapter 3. [Google Scholar] [CrossRef]
- Kuchta, A.; Pacanis, A.; Kortas-Stempak, B.; Çwiklińska, A.; Ziętkiewicz, M.; Renke, M.; Rutkowski, B. Estimation of Oxidative Stress Markers in Chronic Kidney Disease. Kidney Blood Press. Res. 2011, 34, 12–19. [Google Scholar] [CrossRef]
- Lee, Y.-H.; Wong, D.T. Saliva: An emerging biofluid for early detection of diseases. Am. J. Dent. 2009, 22, 241–248. [Google Scholar]
- Bernard, K.; Logsdon, N.J.; Miguel, V.; Benavides, G.A.; Zhang, J.; Carter, A.B.; Darley-Usmar, V.M.; Thannickal, V.J. NADPH Oxidase 4 (Nox4) Suppresses Mitochondrial Biogenesis and Bioenergetics in Lung Fibroblasts via a Nuclear Factor Erythroid-derived 2-like 2 (Nrf2)-dependent Pathway. J. Biol. Chem. 2017, 292, 3029–3038. [Google Scholar] [CrossRef] [PubMed]
- Aranda-Rivera, A.K.; Cruz-Gregorio, A.; Aparicio-Trejo, O.E.; Pedraza-Chaverri, J. Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases. Biomolecules 2021, 11, 1144. [Google Scholar] [CrossRef]
- Tirichen, H.; Yaigoub, H.; Xu, W.; Wu, C.; Li, R.; Li, Y. Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression through Oxidative Stress. Front. Physiol. 2021, 12, 627837. [Google Scholar] [CrossRef] [PubMed]
- Irazabal, M.V.; Torres, V.E. Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease. Cells 2020, 9, 1342. [Google Scholar] [CrossRef] [PubMed]
- Daneshgar, N.; Baguley, A.W.; Liang, P.-I.; Wu, F.; Chu, Y.; Kinter, M.T.; Benavides, G.A.; Johnson, M.S.; Darley-Usmar, V.; Zhang, J.; et al. Metabolic derangement in polycystic kidney disease mouse models is ameliorated by mitochondrial-targeted antioxidants. Commun. Biol. 2021, 4, 1200. [Google Scholar] [CrossRef] [PubMed]
- Helal, I.; McFann, K.; Reed, B.; Yan, X.-D.; Schrier, R.W.; Fick-Brosnahan, G.M. Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease. Nephrol. Dial. Transplant. 2013, 28, 380–385. [Google Scholar] [CrossRef] [PubMed]
- Ferraro, P.M.; Bargagli, M.; Faller, N.; Anderegg, M.A.; Huynh-Do, U.; Vogt, B.; Gambaro, G.; Fuster, D.G. The role of urinary supersaturations for lithogenic salts in the progression of autosomal dominant polycystic kidney disease. J. Nephrol. 2023, 36, 1011–1018. [Google Scholar] [CrossRef]
- Pisano, A.; Cernaro, V.; Gembillo, G.; D’arrigo, G.; Buemi, M.; Bolignano, D. Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2017, 18, 2283. [Google Scholar] [CrossRef]
- Chaudhary, A.; He, Z.; Atwood, D.J.; Miyazaki, M.; Oto, O.A.; Davidoff, A.; Edelstein, C.L. Raising serum uric acid with a uricase inhibitor worsens PKD in rat and mouse models. Am. J. Physiol. Ren. Physiol. 2024, 326, F1004–F1015. [Google Scholar] [CrossRef] [PubMed]
- Brosnahan, G.M.; You, Z.; Wang, W.; Gitomer, B.Y.; Chonchol, M. Serum Uric Acid and Progression of Autosomal Dominant Polycystic Kidney Disease: Results from the HALT PKD Trials. Curr. Hypertens. Rev. 2021, 17, 228–237. [Google Scholar] [CrossRef] [PubMed]
- Lambert, K.; Gardos, R.; Coolican, H.; Pickel, L.; Sung, H.-K.; Wang, A.Y.-M.; Ong, A.C. Diet and Polycystic Kidney Disease: Nutrients, Foods, Dietary Patterns, and Implications for Practice. Semin. Nephrol. 2023, 43, 151405. [Google Scholar] [CrossRef]
- Torres, J.A.; Torres, J.A.; Kruger, S.L.; Kruger, S.L.; Broderick, C.; Broderick, C.; Amarlkhagva, T.; Amarlkhagva, T.; Agrawal, S.; Agrawal, S.; et al. Ketosis Ameliorates Renal Cyst Growth in Polycystic Kidney Disease. Cell Metab. 2019, 30, 1007–1023.e5. [Google Scholar] [CrossRef]
- Shimazu, T.; Hirschey, M.D.; Newman, J.; He, W.; Shirakawa, K.; Le Moan, N.; Grueter, C.A.; Lim, H.; Saunders, L.R.; Stevens, R.D.; et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013, 339, 211–214. [Google Scholar] [CrossRef] [PubMed]
- Strubl, S.; Oehm, S.; Torres, J.A.; Grundmann, F.; Haratani, J.; Decker, M.; Vuong, S.; Bhandal, A.K.; Methot, N.; Haynie-Cion, R.; et al. Ketogenic dietary interventions in autosomal dominant polycystic kidney disease—A retrospective case series study: First insights into feasibility, safety and effects. Clin. Kidney J. 2021, 15, 1079–1092. [Google Scholar] [CrossRef] [PubMed]
- Oehm, S.; Steinke, K.; Schmidt, J.; Arjune, S.; Todorova, P.; Lindemann, C.H.; Wöstmann, F.; Meyer, F.; Siedek, F.; Weimbs, T.; et al. RESET-PKD: A pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease. Nephrol. Dial. Transplant. 2023, 38, 1623–1635. [Google Scholar] [CrossRef] [PubMed]
- Cukoski, S.; Lindemann, C.H.; Arjune, S.; Todorova, P.; Brecht, T.; Kühn, A.; Oehm, S.; Strubl, S.; Becker, I.; Kämmerer, U.; et al. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD—A randomized controlled trial. Cell Rep. Med. 2023, 4, 101283. [Google Scholar] [CrossRef] [PubMed]
- Calvaruso, L.; Yau, K.; Akbari, P.; Nasri, F.; Khowaja, S.; Wang, B.; Haghighi, A.; Khalili, K.; Pei, Y. Real-life use of tolvaptan in ADPKD: A retrospective analysis of a large Canadian cohort. Sci. Rep. 2023, 13, 22257. [Google Scholar] [CrossRef] [PubMed]
- Raina, R.; Houry, A.; Rath, P.; Mangat, G.; Pandher, D.; Islam, M.; Khattab, A.G.; Kalout, J.K.; Bagga, S. Clinical Utility and Tolerability of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Drug Healthc. Patient Saf. 2022, 14, 147–159. [Google Scholar] [CrossRef] [PubMed]
- Rigato, M.; Carraro, G.; Cirella, I.; Dian, S.; Di Vico, V.; Stefanelli, L.F.; Ravarotto, V.; Bertoldi, G.; Nalesso, F.; Calò, L.A. Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach. J. Clin. Med. 2022, 11, 402. [Google Scholar] [CrossRef]
- Fujiki, T.; Ando, F.; Murakami, K.; Isobe, K.; Mori, T.; Susa, K.; Nomura, N.; Sohara, E.; Rai, T.; Uchida, S. Tolvaptan activates the Nrf2/HO-1 antioxidant pathway through PERK phosphorylation. Sci. Rep. 2019, 9, 9245. [Google Scholar] [CrossRef] [PubMed]
- Dubois, E.A.; Rissmann, R.; Cohen, A.F. Tolvaptan. Br. J. Clin. Pharmacol. 2012, 73, 9–11. [Google Scholar] [CrossRef]
- Qi, J.; Gan, L.; Fang, J.; Zhang, J.; Yu, X.; Guo, H.; Cai, D.; Cui, H.; Gou, L.; Deng, J.; et al. Beta-Hydroxybutyrate: A Dual Function Molecular and Immunological Barrier Function Regulator. Front. Immunol. 2022, 13, 805881. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Luo, M.; Bai, X.; Li, J.; Nie, P.; Li, B.; Luo, P. SS-31, a Mitochondria-Targeting Peptide, Ameliorates Kidney Disease. Oxidative Med. Cell. Longev. 2022, 2022, 1295509. [Google Scholar] [CrossRef] [PubMed]
- Sekine, M.; Okamoto, K.; Pai, E.F.; Nagata, K.; Ichida, K.; Hille, R.; Nishino, T. Allopurinol and oxypurinol differ in their strength and mechanisms of inhibition of xanthine oxidoreductase. J. Biol. Chem. 2023, 299, 105189. [Google Scholar] [CrossRef] [PubMed]
- Sims, C.R.; MacMillan-Crow, L.A.; Mayeux, P.R. Targeting mitochondrial oxidants may facilitate recovery of renal function during infant sepsis. Clin. Pharmacol. Ther. 2014, 96, 662–664. [Google Scholar] [CrossRef] [PubMed]
- Arulkumaran, N.; Pollen, S.J.; Tidswell, R.; Gaupp, C.; Peters, V.B.; Stanzani, G.; Snow, T.A.; Duchen, M.R.; Singer, M. Selective mitochondrial antioxidant MitoTEMPO reduces renal dysfunction and systemic inflammation in experimental sepsis in rats. Br. J. Anaesth. 2021, 127, 577–586. [Google Scholar] [CrossRef] [PubMed]
- Aung, Y.Y.M.; Wong, D.C.S.; Ting, D.S.W. The promise of artificial intelligence: A review of the opportunities and challenges of artificial intelligence in healthcare. Br. Med. Bull. 2021, 139, 4–15. [Google Scholar] [CrossRef] [PubMed]
- Monaco, S.; Bussola, N.; Buttò, S.; Sona, D.; Giobergia, F.; Jurman, G.; Xinaris, C.; Apiletti, D. AI models for automated segmentation of engineered polycystic kidney tubules. Sci. Rep. 2024, 14, 2847, Erratum in Sci. Rep. 2024, 14, 4781. [Google Scholar] [CrossRef] [PubMed]
- Shin, J.H.; Kim, Y.H.; Lee, M.K.; Min, H.-S.; Cho, H.; Kim, H.; Kim, Y.C.; Lee, Y.S.; Shin, T.Y. Feasibility of artificial intelligence-based decision supporting system in tolvaptan prescription for autosomal dominant polycystic kidney disease. Investig. Clin. Urol. 2023, 64, 255–264. [Google Scholar] [CrossRef] [PubMed]
- Taylor, J.; Thomas, R.; Metherall, P.; van Gastel, M.; Gall, E.C.-L.; Caroli, A.; Furlano, M.; Demoulin, N.; Devuyst, O.; Winterbottom, J.; et al. An Artificial Intelligence Generated Automated Algorithm to Measure Total Kidney Volume in ADPKD. Kidney Int. Rep. 2023, 9, 249–256, Erratum in Kidney Int. Rep. 2024, 9, 1943. [Google Scholar] [CrossRef] [PubMed]
- Tavakolidakhrabadi, N.; Aulicino, F.; May, C.J.; Saleem, M.A.; Berger, I.; Welsh, G.I. Genome editing and kidney health. Clin. Kidney J. 2024, 17, sfae119. [Google Scholar] [CrossRef]
- Serra, G.; Corsello, G.; Antona, V.; D’alessandro, M.M.; Cassata, N.; Cimador, M.; Giuffrè, M.; Schierz, I.A.M.; Piro, E. Autosomal recessive polycystic kidney disease: Case report of a newborn with rare PKHD1 mutation, rapid renal enlargement and early fatal outcome. Ital. J. Pediatr. 2020, 46, 154. [Google Scholar] [CrossRef]
- Pana, C.; Stanigut, A.M.; Cimpineanu, B.; Alexandru, A.; Salim, C.; Nicoara, A.D.; Resit, P.; Tuta, L.A. Urinary Biomarkers in Monitoring the Progression and Treatment of Autosomal Dominant Polycystic Kidney Disease—The Promised Land? Medicina 2023, 59, 915. [Google Scholar] [CrossRef] [PubMed]
- Vishy, C.E.; Thomas, C.; Vincent, T.; Crawford, D.K.; Goddeeris, M.M.; Freedman, B.S. Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease. Cell Stem Cell 2024, 31, 537–553.e5. [Google Scholar] [CrossRef] [PubMed]
Key Signaling Cascade | Renal and Extra-Renal Consequences |
---|---|
NOX4 | NOX4 is the primary source of ROS generation in renal cells and endothelial cells. Upregulation of NOX4 in PKD generates ROS, causing oxidative stress and endothelial dysfunction. |
XOR | Increased XOR activity in PKD causes hyperuricemia, induction of NOX4, and inhibition of NO synthase. This results in inflammation, ROS production, and endothelial injury. |
NO synthase | Surplus ROS uncouples NO synthase, and increased XOR inhibits NO synthase. Both deplete the NO supply, causing oxidative stress and vascular damage. |
Mitochondrial apoptosis | Excess ROS oxidizes mitochondrial DNA, proteins, and lipids. It impairs cell function and signaling and ATP production, resulting in hypoxia, overactive mitophagy, apoptosis, fibrosis, and inflammation. |
Medication | Author | Year | Methods | Outcomes | Mechanism of Action |
---|---|---|---|---|---|
Tolvaptan | Calvaruso et al. [38] | 2023 | Mayo Clinic Imaging Class (MCIC) and total kidney volume measurements were taken for 523 patients of 18 years or older with confirmed ADPKD to compare the properties of patients undergoing treatment versus patients not undergoing tolvaptan treatment. | In total, 60% (315/523) of patients with ADPKD were considered to be at high risk of progressing to ESKD, but only 30% (96/315) of them were treated with tolvaptan at their respective follow-ups. | Tolvaptan is a competitive antagonist at the V2 vasopressin receptor in the renal collecting ducts. As a result, aquaporin synthesis and transport are improved, leading to better water retention while reducing plasma osmolality. As a result, urine volume is reduced but urinary sodium ion secretion continues [42]. |
Raina et al. [39] | 2022 | The research conducted a systematic review of 22 pieces of literature to determine the side effects, efficacy, and complications of tolvaptan use for ADPKD. | TEMPO 3:4 and REPRISE trials showed a change in eGFR from pre-treatment baseline to post-treatment of 1 mL/min/1.73 and 1.3 mL/min/1.73, respectively, for patients undergoing ADPKD treated with tolvaptan. There was a mean decrease of 49% in total kidney volume from baseline to post-treatment in the TEMPO 3:4 study. | ||
Rigato et al. [40] | 2022 | The research examined the OxSt of 27 patients aged 18–65 through six tests: mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, a marker of Rho kinase activity (Western blot), and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). | The study showed that OxSt is activated in ADPKD and that tolvaptan treatment reduces proteins closely related to OxSt signaling, inflammation, and cardiovascular–renal remodeling and helps induce defense against OxSt. In tolvaptan-treated ADPKD patients, the blood creatinine and eGFR levels were 126.3 ± 13.3 µmol/L and 53.8 ± 4.6 mL/min/1.73 m2, respectively. In contrast, the blood creatinine and eGFR levels in untreated ADPKD patients were 78.67 ± 11.98 µmol/L and 91.44 ± 14.07 mL/min/1.73 m2, respectively. | ||
Fujiki et al. [41] | 2019 | The research used a renal cortical collecting duct cell (mpkCCD) in a cell line and mouse kidneys to determine how tolvaptan and bardoxolone methyl affect Nrf2. | Tolvaptan activated Nrf2 and increased the mRNA and protein expression of antioxidant enzyme heme oxygenase-1 (HO-1) through the phosphorylation of protein kinase RNA-like endoplasmic reticulum kinase. | ||
BHB | Torres et al. [33] | 2019 | The research examined the effects of ketogenic diets in adult PKD rats and the effects of BHB treatments in PKD juvenile rats on renal cyst growth in PKD. | BHB affected numerous pathways implicated in PKD, including mTOR, AMPK, and HDACs. BHB-treated rats had a reduced kidney-to-body weight ratio and cystic area compared with the controls. | BHB directly inhibited class 1 histone deacetylases (HDACs), which is theorized to help regulate gene expression by deacetylating lysine residues on histone and nonhistone proteins, leading to changes in gene expression [43]. BHB makes transcription changes in the stress resistance factors FOXO3A and MT2, which promote oxidative stress resistance in the kidneys. |
Shimazu et al. [34] | 2013 | The research treated human embryonic kidney cells with different amounts of BHB for 8 h to test if BHB has HDAC inhibitor activity, purified and incubated recombinant HDACs to test the inhibitor activity of BHB and its selectivity, and measured the BHB concentration in mouse serum after a 24 h fast to determine if BHB concentrations in vivo affect histone acetylation, all to determine the effectiveness of BHB’s ability to inhibit HDAC. | BHB inhibited HDAC, correlating with changes in gene transcription, including the genes encoding the oxidative stress resistance factors FOXO3A and MT2 through selectively depleting HDAC1 and HDAC2, protecting against oxidative stress. | ||
SS31 | Daneshgar et al. [26] | 2021 | The research treated ADPKD mice models with SS31 to determine how mitochondrial-targeted antioxidants affect ADPKD progression, and ROS, measuring through hemoglobin, BUN, mitochondrial respiratory complex activity, and LDH activity. | SS31 mitigated the progression of APKD-like disease symptoms in mice, reducing mitochondrial ROS and oxidative damage. Kidney staining showed that SS31 reduced the area of kidney cysts and fibrosis in the experimented mice. | SS-31, as a mitochondria-targeting drug, binds to cardiolipin, assists electron transfer, and limits electron linkage. As a result, it protects the structural integrity of the mitochondria, repairs damaged mitochondria, scavenges ROS, and increases the ATP supply, which reduces oxidative stress and improves apoptosis. Additionally, SS31 scavenges mitochondrial ROS and breaks the oxidative stress cycle, preventing renal tissue in diabetes patients. |
Zhu et al. [44] | 2021 | The research analyzes the pharmacokinetics of SS31, arguing for possible mechanisms for its protective effects against renal diseases, and examines previous data about SS31’s uses against renal diseases such as animal and cell models such in vivo studies in rats and in vitro studies in mesangial cells to study the how SS31 alleviates kidney disease symptoms | Compared with the placebo, patients in the SS31 group underwent a lower degree of partial tissue hypoxia. Additionally, only SS31 group patients had increased renal blood flow (202 ± 29 to 262 ± 115 mL/min; p = 0.04) and renal cortical perfusion (1.99 ± 0.8 to 2.9 ± 1 mL/min/mL) three months after percutaneous renal angioplasty. | ||
Oxypurinol | Chaudhary et al. [30] | 2024 | The research measured proinflammatory cytokines, inflammasome, and crystal deposition in the kidneys and the mechanisms of increased cyst growth in PKD mice, PCK rats, and a hepatic disease 1 gene model of autosomal recessive PKD, using a combination of oxonic acid and oxypurinol as a treatment for the PKD mice. | A combination of oxypurinol and oxonic acid significantly reduced the increase in serum uric acid induced by oxonic acid and reduced the kidney weight and the cyst index but did not affect cyst growth in PKD RC/RC mice. | Oxypurinol, in the presence of high concentrations of hypoxanthine and xanthine, binds with xanthine oxidoreductase, inhibiting the hydroxylation of hypoxanthine to xanthine. In turn, it prevents xanthine from converting into uric acid [45]. |
MitoTEMPO | Sims et al. [46] | 2014 | The research examined preclinical studies to investigate how rodent models of SAKI can be used as a therapy to restore renal recovery. | MitoTEMPO might be able to target the sources of oxidants, improving mitochondrial function, microcirculatory perfusion, renal function, and long-term survival outcomes. Rodent models have shown promising results in reducing oxidative stress and helping renal function. | Mito-TEMPO is a selective mitochondrial antioxidant attached to a lipophilic triphenylphosphonium cation, which targets it to the mitochondria, promoting mitochondrial function and restoring renal function by targeting oxidants and allowing the renal microcirculation and tubular epithelium time to recover [47]. |
Arulkumaran et al. [47] | 2021 | The research examined the effects of MitoTEMPO ex vivo using adenosine triphosphate and lipopolysaccharide-stimulated rat peritoneal immune cells and rat kidney slices exposed to septic rat serum and used a fluid-resuscitated rat model of sepsis to assess the effects of MitoTEMPO in vivo. | MitoTEMPO decreased septic serum-induced mROS levels and maintained a normal nicotinamide adenine dinucleotide redox state and mitochondrial membrane potential in renal proximal tubular epithelial cells ex vivo. In vivo, compared with the placebo, the Mito-TEMPO group had reduced renal oxidative stress determined by urine isoprostane levels and improved renal dysfunction. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Subhash, S.; Vijayvargiya, S.; Parmar, A.; Sandhu, J.; Simmons, J.; Raina, R. Reactive Oxygen Species in Cystic Kidney Disease. Antioxidants 2024, 13, 1186. https://doi.org/10.3390/antiox13101186
Subhash S, Vijayvargiya S, Parmar A, Sandhu J, Simmons J, Raina R. Reactive Oxygen Species in Cystic Kidney Disease. Antioxidants. 2024; 13(10):1186. https://doi.org/10.3390/antiox13101186
Chicago/Turabian StyleSubhash, Sanat, Sonya Vijayvargiya, Aetan Parmar, Jazlyn Sandhu, Jabrina Simmons, and Rupesh Raina. 2024. "Reactive Oxygen Species in Cystic Kidney Disease" Antioxidants 13, no. 10: 1186. https://doi.org/10.3390/antiox13101186
APA StyleSubhash, S., Vijayvargiya, S., Parmar, A., Sandhu, J., Simmons, J., & Raina, R. (2024). Reactive Oxygen Species in Cystic Kidney Disease. Antioxidants, 13(10), 1186. https://doi.org/10.3390/antiox13101186