Deneysel Sıçan Sepsis Modelinde Bromelainin Oksidatif Stres ve Akciğer Doku Histopatolojisi Üzerine Etkileri

Öz

Sepsis, inflamatuvar bir sendrom olup başta akciğeri hedef almaktadır. Bromelainin (BRO) anti-inflamatuvar özelliği ile bilinen enzim kompleksidir. Bu çalışmada Sprague dawley sıçanlarında çekal ligasyon ve perforasyon (CLP) ile indüklenen sepsise bağlı akciğer hasarında BRO koruyucu etkisi biyokimyasal ve histopatolojik yöntemlerle araştırıldı. Kırk adet Sprague dawley sıçan, kontrol, CLP, BRO, CLP+BRO 50 ve CLP+BRO 100 olmak üzere rastgele beş gruba ayrıldı. Çalışmada sıçanlara 50 ve 100 mg/kg BRO oral olarak (7 gün boyunca toplam 7 uygulama) verildikten sonra laparotomi ve CLP uygulanmıştır. Veriler, BRO'nun antioksidan özelliklerinden dolayı CLP ile indüklenen miyeloperoksidaz (MPO) ve lipid peroksidasyonu (MDA) azalttığını (p <0,001), glutatyon (GSH) seviyelerini, süperoksit dismutaz (SOD) ve glutatyon peroksidaz (GPx) aktivitelerini arttırdığını göstermiştir (p <0,001). Ayrıca CLP kaynaklı akciğer histolojik değişiklikler BRO takviyesi ile azalmıştır. Sonuçlar BRO tedavisin CLP kaynaklı akciğer toksisitesi üzerinde antioksidan, anti-inflamatuvar etkiye sahip olduğunu ve düzenleyici etkisi sayesinde akciğer doku mimarisinin korunmasına yardımcı olduğunu göstermiştir.

Anahtar Kelimeler

• Akciğer
• Bromelain
• Sepsis
• İnflamasyon
• Oksidatif Stres

Effects of Bromelain on Oxidative Stress and Lung Tissue Histopathology in an Experimental Rat Sepsis Model

Öz

Sepsis is an inflammatory syndrome that targets the lung tissue. Bromelain (BRO) is an enzyme complex known for its anti-inflammatory properties. In this study, the protective effect of BRO on lung injury due to sepsis induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats was investigated by biochemical and histopathological methods. Forty Sprague dawley rats were randomly divided into five groups as control, CLP, BRO, CLP+BRO 50 and CLP+BRO 100. In the study, after oral administration of 50 and 100 mg/kg BRO (total of 7 applications for 7 days) to rats, laparotomy and CLP were performed. The data showed that due to its antioxidant properties, BRO decreased CLP-induced myeloperoxidase (MPO) and lipid peroxidation (MDA) (p <0,001), increased glutathione (GSH) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities (p <0,001). Additionally, CLP-induced lung histological changes were reduced with BRO supplementation. The results showed that BRO treatment has an antioxidant, anti-inflammatory effect on CLP-induced lung toxicity and helps preserve lung tissue architecture owing to its regulatory effect.

Anahtar Kelimeler

• Lung
• Bromelain
• Sepsis
• Inflammation
• Oxidative Stress

Kaynakça

1. Agarwal, S., Chaudhary, B., & Bist, R. (2016). Bacoside A and bromelain relieve dichlorvos induced changes in oxidative responses in mice serum. Chemico-biological interactions, 254, 173–178. https://doi.org/10.1016/j.cbi.2016.05.017
2. Akaras, N., Bal, T., Atilay, H., Selli, J., & Halici, M. B. (2017). Protective effects of agomelatine on testicular damage caused by bortezomib. Biotechnic&histochemistry:official publication of the Biological Stain Commission, 92(8), 552–559. https://doi.org/10.1080/10520295.2017.1350748
3. Akaras, N., Gur, C., Kucukler, S., & Kandemir, F. M. (2023). Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chemico-biological interactions, 374, 110410. https://doi.org/10.1016/j.cbi.2023.110410
4. Anter, A., Ahmed, A. F., Hammad, A. S. A., Almalki, W. H., Abdel Hafez, S. M. N., Kasem, A. W., El-Moselhy, M. A., Alrabia, M. W., Ibrahim, A. R. N., & El-
5. Daly, M. (2022). The Severity of Acute Kidney and Lung Injuries Induced by Cecal Ligation and Puncture Is Attenuated by Menthol: Role of Proliferating Cell Nuclear Antigen and Apoptotic Markers. Frontiers in medicine, 9, 904286. https://doi.org/10.3389/fmed.2022.904286
6. Baradaran Rahimi, V., Rakhshandeh, H., Raucci, F., Buono, B., Shirazinia, R., Samzadeh Kermani, A., Maione, F., Mascolo, N., & Askari, V. R. (2019). Anti-Inflammatory and Anti-Oxidant Activity of Portulaca oleracea Extract on LPS-Induced Rat Lung Injury. Molecules (Basel, Switzerland), 24(1), 139. https://doi.org/10.3390/molecules24010139
7. Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982). Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. The Journal of investigative dermatology, 78(3), 206–209. https://doi.org/10.1111/1523-1747.ep12506462
8. Chen, G., Hou, Y., Li, X., Pan, R., & Zhao, D. (2021). Sepsis-induced acute lung injury in young rats is relieved by calycosin through inactivating the HMGB1/MyD88/NF-κB pathway and NLRP3 inflammasome. International immunopharmacology, 96, 107623. https://doi.org/10.1016/j.intimp.2021.107623

9. Chen, X., Wang, Y., Xie, X., Chen, H., Zhu, Q., Ge, Z., Wei, H., Deng, J., Xia, Z., & Lian, Q. (2018). Heme Oxygenase-1 Reduces Sepsis-Induced Endoplasmic Reticulum Stress and Acute Lung Injury. Mediators of inflammation, 2018, 9413876. https://doi.org/10.1155/2018/9413876
10. Cinar, I., Sirin, B., Aydin, P., Toktay, E., Cadirci, E., Halici, I., & Halici, Z. (2019). Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. Life sciences, 221, 327–334. https://doi.org/10.1016/j.lfs.2019.02.039
11. El-Demerdash, F. M., Baghdadi, H. H., Ghanem, N. F., & Mhanna, A. B. A. (2020). Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats. Environmental toxicology and pharmacology, 80, 103509. https://doi.org/10.1016/j.etap.2020.103509
12. Eraslan, E., Tanyeli, A., Akdemir, F. N. E., & Güler, M. C. (2020). Reno-Protective Effects of 6-Shogaol on Kidney Tissue in Cecal Ligation and Puncture-Induced Polymicrobial Sepsis Rat Model. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 15(3), 244-250.
13. Ferah Okkay, I., Okkay, U., Bayram, C., Cicek, B., Sezen, S., Aydin, I. C., Mendil, A. S., & Hacimuftuoglu, A. (2023). Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation. Drug and chemical toxicology, 46(1), 69–76. https://doi.org/10.1080/01480545.2021.2011308
14. Gerin, F., Sener, U., Erman, H., Yilmaz, A., Aydin, B., Armutcu, F., & Gurel, A. (2016). The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis. Inflammation, 39(2), 700–705. https://doi.org/10.1007/s10753-015-0296-9
15. Giustina, A. D., Danielski, L. G., Novochadlo, M. M., Goldim, M. P. S., Joaquim, L., Metzker, K. L. L., Carli, R. J., Denicol, T., Cidreira, T., Vieira, T., & Petronilho, F. (2019). Vitamin B6 reduces oxidative stress in lungs and liver in experimental sepsis. Anais da Academia Brasileira de Ciencias, 91(4), e20190434. https://doi.org/10.1590/0001-3765201920190434
16. Gur, C., Kandemir, F. M., Caglayan, C., & Satıcı, E. (2022). Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways. Chemico-biological interactions, 365, 110073. https://doi.org/10.1016/j.cbi.2022.110073
17. Cihan, G. Ü. R., Kandemir, Ö., & Kandemir, F. M. (2022). Ratlarda diklofenak ile indüklenen kardiyotoksisite üzerine krisinin etkilerinin oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ile değerlendirilmesi. Kocatepe Veterinary Journal, 15(2), 151-160.
18. Gur, C., Akarsu, S. A., Akaras, N., Tuncer, S. C., & Kandemir, F. M. (2023). Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite-induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats. Environmental toxicology, 38(6), 1265–1276. https://doi.org/10.1002/tox.23762
19. Hu, Q., Wang, Q., Han, C., & Yang, Y. (2020). Sufentanil attenuates inflammation and oxidative stress in sepsis-induced acute lung injury by downregulating KNG1 expression. Molecular medicine reports, 22(5), 4298–4306. https://doi.org/10.3892/mmr.2020.11526
20. Kandemir, F. M., Caglayan, C., Aksu, E. H., Yildirim, S., Kucukler, S., Gur, C., & Eser, G. (2020). Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats. Andrologia, 52(3), e13524. https://doi.org/10.1111/and.13524
21. Kandemir, F. M., Ileriturk, M., & Gur, C. (2022). Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Molecular biology reports, 49(7), 6063–6074. https://doi.org/10.1007/s11033-022-07395-0
22. Khazaeel, K., Rad, O. R., Jamshidian, J., Tabandeh, M. R., Mohammadi, G., & Atashfaraz, A. (2022). Effect of bromelain on sperm quality, testicular oxidative stress and expression of oestrogen receptors in bisphenol-A treated male mice. Andrologia, 54(11), e14584. https://doi.org/10.1111/and.14584
23. Lawrence, R. A., & Burk, R. F. (1976). Glutathione peroxidase activity in selenium-deficient rat liver. Biochemical and biophysical research communications, 71(4), 952–958. https://doi.org/10.1016/0006-291x(76)90747-6
24. Li, L., Wang, H., Zhao, S., Zhao, Y., Chen, Y., Zhang, J., Wang, C., Sun, N., & Fan, H. (2022). Paeoniflorin ameliorates lipopolysaccharide-induced acute liver injury by inhibiting oxidative stress and inflammation via SIRT1/FOXO1a/SOD2 signaling in rats. Phytotherapy research: PTR, 36(6), 2558–2571. https://doi.org/10.1002/ptr.7471
25. Li, R., Ren, T., & Zeng, J. (2019). Mitochondrial Coenzyme Q Protects Sepsis-Induced Acute Lung Injury by Activating PI3K/Akt/GSK-3β/mTOR Pathway in Rats. BioMed research international, 2019, 5240898. https://doi.org/10.1155/2019/5240898
26. Liu, Y., Mu, S., Li, X., Liang, Y., Wang, L., & Ma, X. (2019). Unfractionated Heparin Alleviates Sepsis-Induced Acute Lung Injury by Protecting Tight Junctions. The Journal of surgical research, 238, 175–185. https://doi.org/10.1016/j.jss.2019.01.020
27. Liu, Y., Zhang, Y., Feng, Q., Liu, Q., Xie, J., Li, H., Yang, F., Liu, X., Gao, W., Bai, X., Li, Z., & Wang, Y. (2021). GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage. Oxidative medicine and cellular longevity, 2021, 5589472. https://doi.org/10.1155/2021/5589472
28. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. The Journal of biological chemistry, 193(1), 265–275.
29. Margotti, W., Goldim, M. P. S., Machado, R. S., Bagio, E., Dacoregio, C., Bernades, G., Lanzzarin, E., Stork, S., Cidreira, T., Denicol, T. L., Joaquim, L., Danielski, L. G., Metzker, K. L. L., Bonfante, S., Margotti, E., & Petronilho, F. (2022). Oxidative stress in multiple organs after sepsis in elderly rats. Experimental gerontology, 160, 111705. https://doi.org/10.1016/j.exger.2022.111705
30. Petronilho, F., Florentino, D., Danielski, L. G., Vieira, L. C., Martins, M. M., Vieira, A., Bonfante, S., Goldim, M. P., & Vuolo, F. (2016). Alpha-Lipoic Acid Attenuates Oxidative Damage in Organs After Sepsis. Inflammation, 39(1), 357–365. https://doi.org/10.1007/s10753-015-0256-4
31. Placer, Z. A., Cushman, L. L., & Johnson, B. C. (1966). Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Analytical biochemistry, 16(2), 359–364. https://doi.org/10.1016/0003-2697(66)90167-9
32. Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical biochemistry, 25(1), 192–205. https://doi.org/10.1016/0003-2697(68)90092-4
33. Semis, H. S., Gur, C., Ileriturk, M., Kandemir, F. M., & Kaynar, O. (2022). Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. The American journal of sports medicine, 50(2), 486–498. https://doi.org/10.1177/03635465211059821
34. Simsek, H., & Akaras, N. (2023). Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. International Journal of Medical Biochemistry, 6(2).
35. Sun, Y., Oberley, L. W., & Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical chemistry, 34(3), 497–500.
36. Şehirli, A. Ö., Sayiner, S., Savtekin, G., & Velioğlu-Öğünç, A. (2021). Protective effect of bromelain on corrosive burn in rats. Burns : journal of the International Society for Burn Injuries, 47(6), 1352–1358.
37. Şimşek, H., Akaras, N., Gür, C., Küçükler, S., & Kandemir, F. M. (2023). Beneficial effects of Chrysin on Cadmium-induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene, 875, 147502. Advance online publication. https://doi.org/10.1016/j.gene.2023.147502
38. Turk, E., Kandemir, F. M., Yildirim, S., Caglayan, C., Kucukler, S., & Kuzu, M. (2019). Protective Effect of Hesperidin on Sodium Arsenite-Induced Nephrotoxicity and Hepatotoxicity in Rats. Biological trace element research, 189(1), 95–108. https://doi.org/10.1007/s12011-018-1443-6
39. Yu, H., Liu, Y., Wang, M., Restrepo, R. J., Wang, D., Kalogeris, T. J., Neumann, W. L., Ford, D. A., & Korthuis, R. J. (2020). Myeloperoxidase instigates proinflammatory responses in a cecal ligation and puncture rat model of sepsis. American journal of physiology. Heart and circulatory physiology, 319(3), H705–H721. https://doi.org/10.1152/ajpheart.00440.2020
40. Zeng, M., He, W., Li, L., Li, B., Luo, L., Huang, X., Guan, K., & Chen, W. (2015). Ghrelin attenuates sepsis-associated acute lung injury oxidative stress in rats. Inflammation, 38(2), 683–690. https://doi.org/10.1007/s10753-014-9977-z
41. Zhang, J., Wang, C., Wang, H., Li, X., Xu, J., & Yu, K. (2021). Loganin alleviates sepsis-induced acute lung injury by regulating macrophage polarization and inhibiting NLRP3 inflammasome activation. International immunopharmacology, 95, 107529. https://doi.org/10.1016/j.intimp.2021.107529