Dekspantenol, Sıçanlarda LPS'nin Neden Olduğu Akut Akciğer Hasarında Artan VCAM-1 ve Kaspaz-3 Ekspresyonlarını Azaltarak İnflamasyonu ve Apoptozu İnhibe Eder

Öz

Bu çalışma, D-pantotenik asidin antioksidan, antiapoptotik ve antiinflamatuar özelliklere sahip stabil bir alkolik analoğu olan Dekspantenol'ün (Dex), lipopolisakkarit (LPS) kaynaklı akciğer hasarı üzerindeki etkilerini vasküler hücre adezyon molekülü-1 (VCAM-1) ve kaspaz-3 (cas-3) seviyeleri üzerinden incelemeyi amaçlamaktadır. Çalışmanın deneysel planına göre otuz iki adet Wistar Albino sıçan rastgele dört farklı gruba ayrıldı: Kontrol, LPS (5 mg/kg, intraperitoneal (ip), tek doz), LPS (son Dex uygulamasından 30 dakika önce) + Dex (500 mg/kg, ip, 3 gün boyunca) ve Dex. LPS uygulamasından 6 saat sonra sıçanların akciğer dokuları histopatolojik, immünohistokimyasal ve biyokimyasal incelemeler için alındı. Çalışmanın sonuçlarına göre LPS, akciğerde hiperemi, nötrofil lökosit kemotaksisi ve kalınlaşmış septal dokuya neden oldu. Akciğer dokusunda VCAM-1 düzeylerini artırarak inflamasyonu indükledi ve cas-3 düzeylerini artırarak apoptozu tetikledi. Ayrıca LPS, antioksidan kapasitenin bir belirteci olan total antioksidan status düzeylerini düşürürken, oksidatif stresin göstergeleri olan total oksidant status ve oksidatif stres indeks değerlerini artırdı. Dex, tüm bu değişiklikleri tersine çevirerek ve değerleri normalleştirerek etkisini gösterdi. Bu sonuçlar, Dex'in LPS kaynaklı akut akciğer hasarında toksisiteyi azaltmak için bir koruyucu olarak kullanılabileceğini düşündürdü.

Anahtar Kelimeler

• Akciğer
• Cas-3
• Dekspantenol
• İnflamasyon
• VCAM-1

Dexpanthenol Inhibits Inflammation and Apoptosis in LPS-Induced Acute Lung Injury by Reducing Increased VCAM-1 and Caspase-3 Expressions in Rats

Abstract

This study aims to investigate the effects of Dexpanthenol (Dex), a stable alcoholic analogue of D-pantothenic acid which has anti-oxidant, antiapoptotic, and antiinflammatory properties, on lipopolysaccharide (LPS)-induced lung damage via caspase-3 (cas-3) and vascular cell adhesion molecule-1 (VCAM-1) levels. According to the experimental plan of study, thirty-two Wistar Albino rats were distributed randomly into four groups as control, LPS (5 mg/kg, intraperitoneally (i.p), single dose), LPS (30 minutes before last Dex treatment) + Dex (500 mg/kg, i.p, for 3 days) and Dex. After six hours of LPS application, lung tissues of the rats were taken for histopathological, immunohistochemical and biochemical examinations. According to results of the study, LPS caused hyperemia, neutrophil leukocyte chemotaxis and thickened septal tissue on lung. Inducing inflammation by increasing VCAM-1 expression and triggered apoptosis by increasing cas-3 expression in lung tissue. In addition, LPS decreased total antioxidant status levels, which is a marker of anti-oxidant capacity, and increased oxidative stress index and total oxidant status values, which are indicators of oxidative stress. Dex has shown its effect by reversing all these alterations and normalizing the values. These results suggest that Dex can be used as a preservative to reduce LPS-induced acute toxicity in the lung.

Keywords

• Cas-3
• Dexpanthenol
• Inflammation
• Lung
• VCAM-1

Kaynakça

1. Alapati A, Deosarkar SP, Lanier OL, Qi C, Carlson GE, Burdick MM, Schwartz FL, McCall KD, Bergmeier SC, Goetz DJ. Simple modifications to methimazole that enhance its inhibitory effect on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression by human endothelial cells. Eur J Pharmacol. 2015 Mar 15;751:59-66.
2. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Crit Care Resusc 2005; 7: 319-23.
3. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800.
4. Berger AB, Witte MD, Denault JB, Sadaghiani AM, Sexton KM, Salvesen GS, Bogyo M. Identification of early intermediates of caspase activation using selective inhibitors and activity-based probes. Mol Cell. 2006 Aug;23(4):509-21.
5. Butt Y, Kurdowska A, Allen TC. Acute Lung Injury: A Clinical and Molecular Review. Arch Pathol Lab Med. 2016 Apr;140(4):345-50.
6. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005 Dec;38(12):1103-11.
7. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004b Apr;37(4):277-85.
8. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004a Feb;37(2):112-9.

9. Heise R, Skazik C, Marquardt Y, Czaja K, Sebastian K, Kurschat P, Gan L, Denecke B, Ekanayake-Bohlig S, Wilhelm KP, Merk HF, Baron JM. Dexpanthenol modulates gene expression in skin wound healing in vivo. Skin Pharmacol Physiol. 2012;25(5):241-8.
10. Kose A, Parlakpinar H, Ozhan O, Ermis N, Yildiz A, Vardi N, Cigremis Y. Therapeutic effects of dexpanthenol on the cardiovascular and respiratory systems following cecal ligation and puncture-induced sepsis in rats. Biotech Histochem. 2020 Aug;95(6):428-437.
11. Li-Mei W, Jie T, Shan-He W, Dong-Mei M, Peng-Jiu Y. Anti-inflammatory and anti-oxidative effects of Dexpanthenol on Lipopolysaccharide induced acute lung injury in mice. Inflammation. 2016 Oct;39(5):1757-63.
12. Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM; Acute Lung Injury in Animals Study Group. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011 May;44(5):725-38.
13. Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 2008; 295: L379. Naim R, Shen T, Riedel F, Bran G, Sadick H, Hormann K. Regulation of apoptosis in external auditory canal cholesteatoma by hepatocyte growth factor/scatter factor. ORL J Otorhinolaryngol Relat Spec. 2005;67(1):45-50.
14. Miao X, Cui W. Berberine alleviates LPS-induced apoptosis, oxidation, and skewed lineages during mouse preimplantation development. Biol Reprod. 2022 Jan 12:ioac002.
15. Naim R, Shen T, Riedel F, Bran G, Sadick H, Hormann K. Regulation of apoptosis in external auditory canal cholesteatoma by hepatocyte growth factor/scatter factor. ORL J Otorhinolaryngol Relat Spec. 2005;67(1):45-50.
16. Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS, Kong IK, Chang KT, Lee DS. Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-κB pathways. Neurosci Lett. 2015 Jan 1;584:191-6.
17. Pınar N, Topaloğlu M, Seçinti İE, Büyük E, Kaplan M. Protective effect of dexpanthenol on cisplatin induced nephrotoxicity in rats. Biotech Histochem. 2022 Jan;97(1):39-43.
18. Qureshi MH, Cook-Mills J, Doherty DE, Garvy BA. TNF-alpha-dependent ICAM-1- and VCAM-1-mediated inflammatory responses are delayed in neonatal mice infected with Pneumocystis carinii. J Immunol. 2003 Nov 1;171(9):4700-7.
19. Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002;71:635-700.
20. Shin JY, Kim J, Choi YH, Kang NG, Lee S. Dexpanthenol Promotes Cell Growth by Preventing Cell Senescence and Apoptosis in Cultured Human Hair Follicle Cells. Curr Issues Mol Biol. 2021 Sep 28;43(3):1361-1373.
21. Si-Cong L, Chaoqin R, Ge L, Xu-Ting L, Jin-Liang L, Bin W, Min Z, Wei H, Liang C, Xue G. Platycodon grandiflorum extract attenuates lipopolysaccharide-induced acute lung injury via TLR4/NF-κBp65 pathway in rats. Pak J Pharm Sci. 2021 Nov;34(6):2213-2218.
22. Stettler H, Kurka P, Wagner C, Sznurkowska K, Czernicka O, Böhling A, Bielfeldt S, Wilhelm KP, Lenz H. A new topical panthenol-containing emollient: skin-moisturizing effect following single and prolonged usage in healthy adults, and tolerability in healthy infants. J Dermatolog Treat. 2017 May;28(3):251-257.
23. Ucar M, Aydogan MS, Vardı N, Parlakpınar H. Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Liver Injury. Transplant Proc. 2018 Dec;50(10):3135-3143.
24. Varisco BM. The pharmacology of acute lung injury in sepsis. Adv Pharmacol Sci. 2011;2011:254619.
25. Vogel ME, Idelman G, Konaniah ES, Zucker SD. Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling. J Am Heart Assoc. 2017;6(4):e004820.
26. Wang L, Cao Y, Gorshkov B, Zhou Y, Yang Q, Xu J, Ma Q, Zhang X, Wang J, Mao X, Zeng X, Su Y, Verin AD, Hong M, Liu Z, Huo Y. Ablation of endothelial Pfkfb3 protects mice from acute lung injury in LPS-induced endotoxemia. Pharmacol Res. 2019 Aug;146:104292.