Investigation of the Effects of Cerium Nitrate and Platelet-Rich Plasma Treatments on Lung Tissue Following Burn Injury in Rats Using Histopathological and Immunohistochemical Methods

Abstract

Burn injuries are among the most common physical traumas seen today. Although burns initially appear as damage to the skin, they can actually affect various tissues and organs due to the systemic inflammatory reactions they trigger. One of the primary organs that are rich in blood circulation is the lung tissue. Several natural compounds have been studied for burn wound treatment, among which cerium nitrate (CN) and Platelet-Rich Plasma (PRP) are known for their anti-inflammatory, antioxidant, and antiapoptotic properties. Despite their use in burn treatment, their specific effects on lung tissue following burns remain unclear. Therefore, this study aimed to investigate the protective effects of CN and PRP against damage in lung tissue following thermal burns on the skin. In this study, thermal burn injuries were induced on the skin of rats. In the CN group, rats were exposed to a 0.04 M (molar) cerium nitrate bath solution for 30 minutes after the burn. In the PRP group, 0.1 ml of PRP was subcutaneously injected into the wound areas of the rats. On the 21st day of the study, rats were sacrificed under general anesthesia, and lung tissues were collected. Histopathological analysis of lung tissues after burns revealed bleeding and mononuclear cell infiltrations in the interalveolar regions, leading to thickening. Mononuclear cell infiltrations were also observed around the bronchioles. Immunohistochemical examinations showed severe expressions of Tnf-α and 8-OHdG in lung tissues after burns. However, in the groups treated with CN and PRP, the histopathological and immunohistochemical findings approached normal values after burn injury. In conclusion, CN and PRP demonstrated protective effects against damage in lung tissue following burn injury.

Keywords

• Burn
• cerium nitrate
• inflammation
• lung
• platelet-rich plasma.

Ratlarda Yanık Sonrası Seryum Nitrat ve Plateletten Zengin Plazma Tedavilerinin Akciğer Dokusu Üzerine Etkilerinin Histopatolojik ve İmmünohistokimyasal Yöntemlerle Araştırılması

Abstract

Yanık, günümüzde en yaygın görülen fiziksel travmaların başında gelmektedir. Yanık ilk bakışta deride oluşan bir hasar olarak görülse de aslında vücudun genelinden oluşturmuş olduğu sistemik yangısal reaksiyonlar sonucunda birçok doku ve organı etkileyebilmektedir. Bunların başında ise kan dolaşımı yönünden zengin olan akciğer dokusu yer almaktadır. Yanık yarası tedavisinde birçok doğal bileşen çalışmalarda kullanılmıştır. Antiinflamatuvar, antioksidan ve antiapoptotik etkinlikleri bilinen Seryum Nitrat (SN) ve Plateletten Zengin Plazma (PZP) bu doğal maddeler arasında yer almaktadır. Bu doğal maddeler her ne kadar yanık tedavisinde kullanılsa da yanık sonrası akciğer dokularında nasıl bir etki ettiği net bir şekilde bilinmemektedir. Bu sebeple, deride oluşturulan termal yanık sonrasında akciğer dokusunda meydana gelen hasara karşı SN ve PZP’ nin koruyucu etkinlikleri bu çalışmada araştırıldı. Ratlarda deride çalışmanın ilk gününde termal yanık hasarı oluşturuldu. SN grubunda yanık sonrası 0.04 molar Seryum Nitrat banyo solüsyonunda ratlar 30 dakika boyunca bekletildi. PZP grubunda ise ratların yara bölgelerine 0.1 ml’lik PZP deri altı enjekte edildi. Çalışmanın 21. gününün sonunda ratlar genel anestezi altında sakrifiye edildi ve akciğer dokuları alındı. Akciğer dokularında yanık sonrasında histopatolojik olarak; interalveoler bölgelerde kanama ile mononükleer hücre infiltrasyonları ve buna bağlı olarak kalınlaşma gözlendi. Bronşiollerin etrafında mononükleer hücre infiltrasyonları görüldü. İmmünohistokimyasal incelemelerde; yanık sonrası akciğer dokularında şiddetli Tnf-α ve 8-OHdG ekspresyonları gözlendi. SN ve PZP uygulanan gruplarda ise yanık sonrası oluşan histopatolojik ve immünohistokimyasal bulguların normal değerlere yaklaştığı tespit edildi. Sonuç olarak; yanık sonrası akciğer dokusunda oluşan hasarlara karşı SN ve PZP’ nin koruyucu etkinliği olduğu ortaya konuldu.

Keywords

• Akciğer
• inflamasyon
• plateletten zengin plazma
• seryum nitrat
• yanık.

References

1. AbuBakr, H. O., Aljuaydi, S. H., Abou-Zeid, S. M., El-Bahrawy, A (2018). Burn-induced multiple organ injury and protective effect of lutein in rats. Inflammation, 41, 760-772.
2. Ameer, L. A. A., Raheem, Z. J., Abdulrazaq, S. S., Ali, B. G., Nasser, M. M., Khairi, A. W. A. (2018). The anti-inflammatory effect of the platelet-rich plasma in the periodontal pocket. European Journal of Dentistry, 12(04), 528-531.
3. Baskaran, H., Yarmush, M. L., Berthiaume, F. (2000). Dynamics of tissue neutrophil sequestration after cutaneous burns in rats. Journal of Surgical Research, 93: 88 –96. https://doi.org/10.1006/jsre.2000.5955
4. Bazzi, A., Ghazanfari, M. J., Norouzi, M., Mobayen, M., Jafaraghaee, F., Zeydi, A. E., Osuji, J., Karkhah, S. (2022). Adherence to referral criteria for burn patients; a systematic review. Archives of Academic Emergency Medicine, 10(1). doi: 10.22037/aaem.v10i1.1534
5. Cai, W., Shen, K., Ji, P., Jia, Y., Han, S., Zhang, W., Hu, X., Yang, X., Han, J., Hu, D. (2022). The Notch pathway attenuates burn-induced acute lung injury in rats by repressing reactive oxygen species. Burns Trauma, 10, tkac008. https://doi.org/10.1093/burnst/tkac008
6. Church, D., Elsayed, S., Reid, O., Winston, B., Lindsay, R. (2006). Burn wound infections. Clinical microbiology reviews, 19(2), 403-434. Doi:https://doi.org/10.1128/cmr.19.2.403-434.2006
7. Clancy, K. D., Lorenz, K., Dries, D., Gamelli, R. L., Hahn, E. L. (2000). Chlorpromazine modulates cytokine expression in the liver and lung after burn injury and endotoxemia. Journal of Trauma and Acute Care Surgery, 48(2), 215-223.
8. Clancy, K. D., Lorenz, K., Hahn, E., Christiansen, B., Hofmann, C., Gamelli, R. L. (1997). Down-regulation of tissue specific tumor necrosis factor-alpha in the liver and lung after burn injury and endotoxemia. Journal of Trauma and Acute Care Surgery, 42(2), 169-176.

9. Csontos, C., Rezman, B., Foldi, V., Bogar, L., Drenkovics, L., Röth, E., Lantos, J. (2012). Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn. Burns, 38(3), 428-437.
10. Deldar, R., D'Arpa, P., Moffatt, L., Leung, K., Shupp, J. (2022). Cerium nitrate treatment in the management of burns. Advances in Wound Care, 11(8), 443-454.
11. Deniz, M., Borman, H., Seyhan, T., Haberal, M. (2013). An effective antioxidant drug on prevention of the necrosis of zone of stasis: N-acetylcysteine. Burns, 39, 320–5. https://doi.org/10.1016/j.burns.2012.06.015
12. Deveci, M., Eski, M., Sengezer, M., Kisa, U. (2000). The effect of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-a levels in burned rat. Burns, 26, 41–5. https://doi.org/10.1016/S0305-4179(99)00107-2
13. Dokumacioğlu, E., Iskender, H., Terim Kapakin, K. A., Yenice, G., Mokthare, B., Bolat, İ., Hayirli, A. (2021). Effect of betulinic acid administration on TLR-9/NF-ΚB/IL-18 levels in experimental liver injury. Turkish Journal of Medical Sciences, 51(3), 1544-1553. Doi: 10.3906/sag-2004-184.
14. Eski, M., Ozer, F., Fırat, C., Alhan, D., Arslan, N., Senturk, T., Isık, S. (2012). Cerium nitrate treatments prevent progresive tissue necrosis in the zone of stasis following burn. Burns, 38, 283-289. https://doi.org/10.1016/j.burns.2011.08.008
15. Fang, Y., Xu, P., Gu, C., Wang, Y., Fu, X. J., Yu, W. R., Yao, M. (2011). Ulinastatin improves pulmonary function in severe burn-induced acute lung injury by attenuating inflammatory response. Journal of Trauma and Acute Care Surgery, 71(5), 1297-1304. 10.1097/TA.0b013e3182127d48.
16. Gärtner, R., Albrich, W., Angstwurm, M. W. (2001). The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma. Biofactors, 14(1-4), 199-204.
17. Grambart, S. T. (2015). Sports mediçine and platelet-rich plasma: nonsurgical therapy. Clinics in podiatric medicine and surgery, 32, 99-107. DOI:https://doi.org/10.1016/j.cpm.2014.09.006
18. Hassan, M. A., El Bohy, K. M., El Sharkawy, N. I., Imam, T. S., El‐Metwally, A. E., Hamed Arisha, A., Abd‐Elhakim, Y. M. (2021). Iprodione and chlorpyrifos induce testicular damage, oxidative stress, apoptosis and suppression of steroidogenic‐and spermatogenic‐related genes in immature male albino rats. Andrologia, 53(4), e13978. https://doi.org/10.1111/and.13978
19. Hatherill, J. R., Till, G. O., Bruner, L. H., Ward, P. A. (1986). Thermal injury, intravascular hemolysis, and toxic oxygen products. The Journal of Clinical Investigation, 78(3), 629-636.
20. Iskender, H., Dokumacioglu, E., Terim Kapakin, K. A., Bolat, I., Mokhtare, B., Hayirli, A., Yenice, G. (2023). Effect of Oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes. Journal of Diabetes and Metabolic Disorders, 1-10.
21. Jeschke, M. G., Rehou, S., McCann, M. R., Shahrokhi, S. (2019). Allogeneic mesenchymal stem cells for treatment of severe burn injury. Stem cell research and therapy, 10(1), 1-6.
22. Jeschke, M.G., Van Baar, M.E., Choudhry, M.A., Chung, K.K., Gibran, N.S., Logsetty, S. (2020). Burn injury. Nature Reviews Disease Primers, 6(1), 11.
23. Kayapınar, M., Seyhan, N., Avunduk, M. C., Savacı, N. (2015). Saving the zone of stasis in burns with melatonin: an experimental study in rats. Ulusal Travma Acil Cerrahi Dergisi, 21, 419-424. DOI: 10.5505/tjtes.2015.53059
24. Khan, A., Shal, B., Naveed, M., Nasir, B., Irshad, N., Ali, H., Khan, S. (2020). Matrine alleviates neurobehavioral alterations via modulation of JNK-mediated caspase-3 and BDNF/VEGF signaling in a mouse model of burn injury. Psychopharmacology, 237(8), 2327-2343.
25. Lana, J. F., Huber, S. C., Purita, J., Tambeli, C. H., Santos, G. S., Paulus, C., Annichino-Bizzacchi, J. M. (2019). Leukocyte-rich PRP versus leukocyte-poor PRP-The role of monocyte/macrophage function in the healing cascade. Journal of Clinical Orthopaedics and Trauma, 10, S7-S12.
26. Ma, J., Wang, Y., Wu, Q., Chen, X., Wang, J., Yang, L. (2017). Seawater immersion aggravates burn-associated lung injury and inflammatory and oxidative-stress responses. Burns, 43(5), 1011-1020. Oldham, K. T., Guice, K. S., Till, G. O., Ward, P. A. (1988). Activation of complement by hydroxyl radical in thermal injury. Surgery, 104(2), 272-279.
27. Ozturk, S., Karagoz, H. (2015). Experimental stem cell therapies on burn wound: Do source, dose, timing and method matter?. Burns, 41, 1133-1139. https://doi.org/10.1016/j.burns.2015.01.005
28. Pruitt, J. R., Basıl, A., Daryl, R., Erickson, A., Alan, M. (1975). Progressive pulmonary insufficiency and other pulmonary complications of thermal injury. Journal of Trauma and Acute Care Surgery, 15(5),269-379.
29. Qian, L. W., Fourcaudot, A. B., Chen, P., Brandenburg, K. S., Weaver Jr, A. J., Leung, K. P. (2020). Cerium nitrate enhances anti-bacterial effects and imparts anti-inflammatory properties to silver dressings in a rat scald burn model. International Journal of Burns and Trauma, 10(4), 91.
30. Rathod, M. R., Goswami, H., Jankar, D. (2014). A study of histopathological changes in burn deaths at civil hospital Ahmedabad-Gujarat. Int J Res Med, 3(1), 42-45.
31. Robertson, C. M., Coopersmith, C. M. (2006). The systemic inflammatory response syndrome. Microbes and Infection, 8(5), 1382-1389. https://doi.org/10.1016/j.micinf.2005.12.016
32. Sabeh, F., Boxter, C. R., & Norton, S. J. (1995). Skin burn injury and oxidative stress in liver and lung tissues of rabbit models. Eur J Clin Chem Clin Biochem, 33:323-328.
33. Sheidegger, D., Sparkes, B. G., Luscher, N., Schonenberger, G. A., Allgower, M. (1992). Survival in majör burns treat ed by one bathing in cerium nitrate. Burns, 18, 296–300.
34. Şahin, Y., Gün Gök, Z., Alçığır, M. E., Çınar, M. (2023). Effects Of Functional Poly (Ethylene Terephthalate) Nanofibers Modified With Sericin-Capped Silver Nanoparticles On Histopathological Changes İn Parenchymal Organs And Oxidative Stress İn A Rat Burn Wound Model. Ankara Universitesi Veteriner Fakultesi Dergisi, 70(2), 131-140. DOI: 10.33988/auvfd.990270
35. Şengezer, M., Selmanpakoğlu, N., Duman, H., Çetin, C. (1995). Epidemiological analysis of burn injuries in Gülhane Military Medical Academy Burn Center. Türk Plast Cer Derg, 3(1), 74-7.
36. Terim Kapakin, K. A., Imik, H., Gumus, R., Kapakin, S., Saglam, Y. S. (2013). Effect of Vit E on secretion of HSP-70 in testes of broilers exposed to heat stress. Kafkas Universitesi Veteriner Fakultesi Dergisi, 19(2). DOI: 10.9775/kvfd.2012.7771
37. Venter, N. G., Marques, R. G., Dos Santos, J. S., Monte-Alto-Costa, A. (2016). Use of platelet-rich plasma in deep second-and third-degree burns. Burns, 42(4), 807-814. doi: 10.1016/j.burns. 2016.01.002.
38. Xie, X., Zhang, C., Tuan, R. S. (2014). Biology of platelet-rich plasma and its clinical application in cartilage repair. Arthritis research and therapy, 16, 1-15.