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Hidrojen Sülfür’ün Fizyolojik ve Patolojik Olaylara Katkısı ve Klinikte Kullanımı

Yıl 2022, Cilt: 31 Sayı: 2, 122 - 131, 30.06.2022
https://doi.org/10.17827/aktd.1066415

Öz

Enzimatik veya non-enzimatik yollarla sentezlenen hidrojen sülfür (H2S), nitrik okside (NO) ve karbonmonoksite (CO) benzer üçüncü bir gaz nörotransmitterdir. Vücutta sentezinden sorumlu enzimler çeşitli dokularda eksprese edilmektedir. Antiinflamatuvar, antiapoptotik, nöroprotektif, gastroprotektif, antispazmotik, sitoprotektif, antioksidan, bronkodilatör, kan basıncı regülasyonu gibi birçok fizyolojik etkisi olan H2S’in, hipertansiyon, ateroskleroz, depresyon, astım, kronik obstrüktif akciğer hastalığı, ülser, erektil disfonksiyon, parkinson ve alzheimer gibi çeşitli patolojik durumlarda da rolü olduğu bilinmektedir. Fizyopatolojik durumlardaki potansiyel önemi göz önüne alınarak H2S salıveren aspirin ve naproksenle kombine çeşitli preperatlar geliştirilmiştir. Bu kapsamda antiinflamatuvar, analjezik, antioksidan, sitoprotektif ve kardiyoprotektif etkiler gösteren bazı aday ilaçlar geliştirilmiştir. ATB-346, GIC-1001, NBS-1120, SG-1002, AP-39 ve MZe76 aday ilaçlar arasında yer almaktadır. S-zofenoprilin isimli ilacın ise faz çalışmaları tamamlanmıştır. L-sistein/H2S yolağıyla ilgili preklinik ve klinik araştırmaların gerçekleştirilmesi fizyolojik, patolojik ve terapötik açıdan önem taşımakta ve bu doğrultuda yeni preperatların geliştirilmesinin tedavi yaklaşımları için umut verici olduğu düşünülmektedir.

Kaynakça

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Contribution of Hydrogen Sulfide to Physiological and Pathological Events and Clinical Use

Yıl 2022, Cilt: 31 Sayı: 2, 122 - 131, 30.06.2022
https://doi.org/10.17827/aktd.1066415

Öz

Hydrogen sulfide (H2S), synthesized by enzymatic or non-enzymatic means, is a third gas neurotransmitter similar to nitric oxide (NO) and carbon monoxide (CO). Enzymes responsible for their synthesis in the body are expressed in various tissues. H2S has many physiological effects such as anti-inflammatory, antiapoptotic, neuroprotective, gastroprotective, antispasmodic, cytoprotective antioxidant, a bronchodilator, blood pressure regulation. Also, it is known that H2S has a role in various pathological conditions such as hypertension, atherosclerosis, depression, asthma, chronic obstructive pulmonary disease (COPD), ulcer, erectile dysfunction, Alzheimer's, and Parkinson's disease. Considering its potential importance in physiopathological conditions, various drugs have been developed in combination with H2S-releasing aspirin and naproxen. In this context, some drugs with anti-inflammatory, analgesic, antioxidant, cytoprotective, and cardioprotective effects have been developed. ATB-346, GIC-1001, NBS-1120, SG-1002, AP-39, and MZe76 are among the candidate drugs. Phase studies of S-zofenopril have been completed. The realization of preclinical and clinical studies on the L-cysteine/H2S pathway is important physiologically, pathologically, and therapeutically, and the development of new drugs in this direction is considered to be promising for treatment approaches.

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  • 103. Gratzke C, Streng T, Waldkirch E, Sigl K, Stief C, Andersson KE et al. Transient receptor potential A1 (TRPA1) activity in the human urethra--evidence for a functional role for TRPA1 in the outflow region. Eur Urol. 2009; 55(3):696-704.
  • 104. Srilatha B, Adaikan PG, Moore PK. Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction--a pilot study. Eur J Pharmacol. 2006; 535(1-3): 280-2.
  • 105. Srilatha B, Adaikan PG, Li L, Moore PK. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med. 2007; 4(5):1304-11.
  • 106. Yetik-Anacak G, Dereli MV, Sevin G, Ozzayım O, Erac Y, Ahmed A. Resveratrol Stimulates Hydrogen Sulfide (H2 S) Formation to Relax Murine Corpus Cavernosum. J Sex Med. 2015; 12(10):2004-12.
  • 107. Aydinoglu F, Ogulener N. Characterization of relaxant mechanism of H2 S in mouse corpus cavernosum. Clin Exp Pharmacol Physiol. 2016; 43(4):503-11.
  • 108. Aydinoglu F, Dalkir FT, Demirbag HO, Ogulener N. The interaction of l-cysteine/H2S pathway and muscarinic acetylcholine receptors (mAChRs) in mouse corpus cavernosum. Nitric Oxide. 2017; 70:51-58.
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  • 110. Wang P, Zhang G, Wondimu T, Ross B, Wang R. Hydrogen sulfide and asthma. Exp Physiol. 2011; 96(9):847-52.
  • 111. Rashid S, Heer JK, Garle MJ, Alexander SP, Roberts RE. Hydrogen sulphide-induced relaxation of porcine peripheral bronchioles. Br J Pharmacol. 2013; 168(8):1902-10.
  • 112. Kubo S, Doe I, Kurokawa Y, Kawabata A. Hydrogen sulfide causes relaxation in mouse bronchial smooth muscle. J Pharmacol Sci. 2007; 104(4):392-6.
  • 113. Chen YH, Yao WZ, Gao JZ, Geng B, Wang PP, Tang CS. Serum hydrogen sulfide as a novel marker predicting bacterial involvement in patients with community-acquired lower respiratory tract infections. Respirology. 2009; 14(5):746-52.
  • 114. Chung KF. Hydrogen sulfide as a potential biomarker of asthma. Expert Rev Respir Med. 2014; 8(1):5-13
  • 115. Suzuki Y, Saito J, Munakata M, Shibata Y. Hydrogen sulfide as a novel biomarker of asthma and chronic obstructive pulmonary disease. Allergol Int. 2021; 70(2):181-189.
  • 116. Chen YH, Wu R, Geng B, Qi YF, Wang PP, Yao WZ et al. Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma. Cytokine. 2009; 45(2):117-23.
  • 117. Zhang G, Wang P, Yang G, Cao Q, Wang R. The inhibitory role of hydrogen sulfide in airway hyperresponsiveness and inflammation in a mouse model of asthma. Am J Pathol. 2013; 182(4):1188-95.
  • 118. Tian M, Wang Y, Lu YQ, Yan M, Jiang YH, Zhao DY. Correlation between serum H2S and pulmonary function in children with bronchial asthma. Mol Med Rep. 2012; 6(2):335-8.
  • 119. Chen YH, Wang PP, Wang XM, He YJ, Yao WZ, Qi YF et al. Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung. Cytokine. 2011; 53(3):334-41.
  • 120. Wallace JL, Caliendo G, Santagada V, Cirino G. Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346). Br J Pharmacol. 2010; 159(6):1236-46.
  • 121. Blackler R, Syer S, Bolla M, Ongini E, Wallace JL. Gastrointestinal-sparing effects of novel NSAIDs in rats with compromised mucosal defence. PLoS One. 2012; 7(4):e35196.
  • 122. Magierowski M, Magierowska K, Surmiak M, Hubalewska-Mazgaj M, Kwiecien S, Wallace JL et al. The effect of hydrogen sulfide-releasing naproxen (ATB-346) versus naproxen on formation of stress-induced gastric lesions, the regulation of systemic inflammation, hypoxia and alterations in gastric microcirculation. J Physiol Pharmacol. 2017; 68(5):749-756.
  • 123. Wallace JL, Nagy P, Feener TD, Allain T, Ditrói T, Vaughan DJ et al. A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug. Br J Pharmacol. 2020; 177(4):769-777.
  • 124. De Cicco P, Panza E, Ercolano G, Armogida C, Sessa G, Pirozzi G et al. ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo. Pharmacol Res. 2016; 114:67-73.
  • 125. Paul-Clark M, Elsheikh W, Kirkby N, Chan M, Devchand P, Agbor TA et al. Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis. PLoS One. 2016; 11(2):e0147289.
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  • 138. Rezai H, Ahmad S, Alzahrani FA, Sanchez-Aranguren L, Dias IH, Agrawal S et al. MZe786, a hydrogen sulfide-releasing aspirin prevents preeclampsia in heme oxygenase-1 haplodeficient pregnancy under high soluble flt-1 environment. Redox Biol. 2021; 38:101768.
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  • 140. Sanchez-Aranguren LC, Rezai H, Ahmad S, Alzahrani FA, Sparatore A, Wang K et al. MZe786 Rescues Cardiac Mitochondrial Activity in High sFlt-1 and Low HO-1 Environment. Antioxidants. 2020; 9(7):598.
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  • 142. DRUGBANKonline. Erişim tarihi: 28.04.2021. Available from: https://go.drugbank.com/drugs/DB13166) 2021.
Toplam 142 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Derleme
Yazarlar

Kübra Gönbe Bu kişi benim 0000-0002-8143-3021

Fatma Aydınoğlu 0000-0003-3691-208X

Nuran Öğülener Bu kişi benim 0000-0002-0716-3422

Yayımlanma Tarihi 30 Haziran 2022
Kabul Tarihi 12 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 31 Sayı: 2

Kaynak Göster

AMA Gönbe K, Aydınoğlu F, Öğülener N. Hidrojen Sülfür’ün Fizyolojik ve Patolojik Olaylara Katkısı ve Klinikte Kullanımı. aktd. Haziran 2022;31(2):122-131. doi:10.17827/aktd.1066415