Effect of Folic Acid in Sepsis-induced Lung Damage in Rats

Year 2023, Volume: 5 Issue: Supplement (1) - Innovations in Medicine and Healthcare in the 100th Year of the Republic, 87 - 92, 19.10.2023

Guner Yurtsever , Ejder Saylav Bora , Ebru Eroğlu , Yiğit Uyanıkgil , Mümin Alper Erdoğan , Oytun Erbaş

https://doi.org/10.37990/medr.1348817

Abstract

Aim: Sepsis-induced lung injury remains a critical concern with significant morbidity and mortality. This study aimed to investigate the potential therapeutic role of Folic Acid in mitigating lung injury induced by sepsis while exploring its interaction with the soluble suppression of tumorigenicity 2 (sST2) protein in an experimental rat model.
Material and Methods: Rats were divided into three groups: a normal control group, a group induced with sepsis and treated with saline, and a group induced with sepsis and treated with Folic Acid (5 mg/kg). Biomarkers of oxidative stress, inflammation, respiratory gas exchange, and lung histopathology were assessed.
Results: Folic Acid administration resulted in significantly decreased Malondialdehyde (MDA) levels (p<0.01) and reduced soluble ST2 levels (p<0.05) compared to the sepsis-induced saline group. Tumor necrosis factor α (TNFα) levels were markedly reduced (p<0.001), and lung histopathology demonstrated decreased alveolar inflammation and septal thickness. Additionally, improved oxygenation (PaO2) was observed following Folic Acid treatment (p<0.05), while PaCO2 remained stable.
Conclusion: These findings suggest that Folic Acid protects against sepsis-induced lung injury, ameliorating oxidative stress, inflammation, and histopathological alterations. The modulation of soluble ST2 levels may implicate Folic Acid's role in immune regulation and potential crosstalk with the IL-33/ST2 pathway. Despite promising results, limitations inherent to animal models and the complexities of clinical translation warrant further investigation. This study highlights the potential of Folic Acid as a therapeutic intervention in sepsis-induced lung injury. It underscores the need for mechanistic studies and clinical trials to validate its effectiveness in human patients.

Keywords

Sepsis, Acute lung injury, Soluble ST2, Folic Acid

References

• Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:801-10.
• Seymour CW, Kennedy JN, Wang S, et al. Derivation, valida-tion, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321:2003-17.
• Gavelli F, Castello LM, Avanzi GC. Management of sepsis and septic shock in the emer-gency department. Intern Emerg Med. 2021;16:1649-61.
• Griffiths MJD, McAuley DF, Perkins GD, et al Guidelines on the management of acute respiratory distress syndrome BMJ Open Respir Res. 2019;6:e000420.
• Senousy SR, El-Daly M, Ibrahim ARN, et al. Effect of celecoxib and infliximab against multiple organ damage induced by sepsis in rats: a comparative study. Biomedicines, 2022;10:1613.
• Alsaegh H, Eweis H, Kamal F, Alrafiah A. Celecoxib decrease seizures susceptibility in a rat model of inflammation by inhibiting HMGB1 translocation. Pharmaceuticals (Basel). 2021;14:380.
• Sijilmassi O. Folic acid deficiency and vision: a review. Graefes Arch Clin Exp Ophthalmol. 2019;257:1573-80.
• Maekawa A, Nakajima H, Kawata T. [Folic acid]. Nihon Rinsho. 1999;57:2254-60.
• Griesenauer B, Paczesny S. The ST2/IL-33 axis in immune cells during inflammatory diseases. Front Immunol. 2017;8:475.
• Homsak E, Gruson D. Soluble ST2: A complex and diverse role in several diseases. Clin Chim Acta. 2020;507:75-87.
• Rezan Karaali, Ejder Saylav Bora, Hüseyin Acar, et al. Exploring beta blockers’ efficacy in sepsis-induced acute lung injury and HMGB1-sRAGE interaction. International Journal of Pharmacology. 2023;19:296-304.
• Dibekoğlu C, Uyanıkgil Y, Erbaş O. Sulfasalazine prevents lung injury due to intra-abdominal sepsis in rats: possible role of Nrf2 and angiopoietin-2. Braz J Med Biol Res. 2023;56:e12698.
• Bora ES, Erdoğan MA, Özkul B, et al. Short term protective effect of digitoxin in sepsis-induced acute lung injury. BIOCELL. 2022;46:433-9.
• Erdogan A, Erdogan MA, Kara AY, et al. Effect of fluid resuscitation on acute lung injury in a rat model of sepsis. Bratisl Lek Listy. 2021;122:280-6.
• Novochadlo M, Goldim MP, Bonfante S, et al. Folic acid alleviates the blood brain barrier permeability and oxidative stress and prevents cognitive decline in sepsis-surviving rats. Microvascular Research. 2021;137:104193.
• Lai KG, Chen CF, Ho CT, et al. Novel roles of folic acid as redox regulator: Modulation of reactive oxygen species sinker protein expression and maintenance of mitochondrial redox homeostasis on hepatocellular carcinoma. Tumour Biol. 2017;39:1010428317702649.
• Singh R, Kanwar SS, Sood PK, Nehru B. Beneficial effects of folic acid on enhancement of memoryand antioxidant status in aged rat brain. Cell Mol Neurobiol. 2011;31:83-91.
• Shalaby MA, El Zorba HY, Ziada RM. Reproductive toxicity of methomyl insecticide in male rats and protective effectof folic acid. Food Chem Toxicol. 2010;48:3221-6.
• Hoogerwerf JJ, Tanck MW, van Zoelen MA, et al. Soluble ST2 plasma concentrations predict mortality in severe sepsis. Intensive Care Med. 2010;36:630-7.
• Hur M, Kim H, Kim HJ, et al.; GREAT Network. Soluble ST2 has a prognostic role in patients with suspected sepsis. Ann Lab Med. 2015;35:570-7.
• Kawami M, Harabayashi R, Harada R, et al. Folic acid prevents methotrexate-induced epithelial-mesenchymal transition via suppression of secreted factors from the human alveolar epithelial cell line A549. Biochem Biophys Res Commun. 2018;497:457-63.
• Stampalija T, Chaiworapongsa T, Romero R, et al. Soluble ST2, a modulator of the inflammatory response, in preterm and term labor. J Matern Fetal Neonatal Med. 2014;27:111-21.