The Importance of Aminoguanidine and Methylprednisolone Administration in Lung Contusion after Chest Trauma

Abstract

ABSTRACT Background: This study aims to evaluate the effect of the antioxidant and antiinflammatory properties of aminoguanidine and metylprednisolone (MP) on lung tissue in a pulmonary contusion model of rats and evaluate whether their combined use improves treatment efficacy. Methods: This study included 35 female Sprague Dawley rats weighing 250-300 grams. The rats were divided into five groups as following: Sham; Pulmonary Contusion (PC); PC+MP, PC group treated with i.p methylprednisolone; PC+AG, PC group treated with i.p Aminoguanidine; and PC+AG+MP, PC group treated with Aminoguanidine and methylprednisolone. Each group had seven animals. Blood and lung tissues were studied biochemically and histopathologically. Results: When compared groups according to serum levels of biomarkers, serum YKL-40, nitrate-nitrite, catalase, and TBARS levels were significant different. Serum YKL-40 levels were decreased after treatments in three groups. The serum YKL-40 levels in PC+AG group were lower than the other treatment groups, especially compared to PC + MP (p=0,028). Serum nitrate-nitrite levels were decreased in all treatment groups (PC+MP, PC+AG and PC+MP+AG). The lowest levels were measured in PC+MP+AG; but there was no statistically significant difference compared to PC group (p>0.05). Serum catalase levels were increased in all treatment groups. The higher levels were measured in PC+MP+AG than the other single treatment groups; however PC+MP+AG and PC+MP were statistically significant different compared to PC group (p=0,001 and p=0,002 respectively). Serum TBARS levels were decreased in all treatment groups compared to Sham group (p<0.001) and PC group (p<0.001). The lowest levels were measured in PC+MP+AG compared to PC group (p<0.001). Histopatologic and immunohistochemical staining scores were decreased at all the treatment groups, especially PC+MP+AG. Conclusions: We suggest the use of combined treatment of methylprednisolone and aminoguanidine for the treatment of pulmonary contusion.

Keywords

• oxidative stress
• lung contusion
• aminoguanidine
• methylprednisolone

References

1. 1. 10 Leading Causes of Death by Age Group, United Sates – 2017. Centers For Disease Control and Prevention. February 7, 2019; Accessed: March 18, 2019; Available at https://www.cdc.gov/injury/wisqars/pdf/leading_causes_of_death_by_age_group_2017-508.pdf.
2. 2. Raghavendran K, Davidson BA, Helinski JD, Marschke CJ, Manderscheid P, Woytash JA, et al. A rat model for isolated bilateral lung contusion from blunt chest trauma. Anesthesia & Analgesia. 2005;101(5):1482-9.
3. 3. Matthay MA, Ware LB, Zimmerman GA. The acute respiratory distress syndrome. The Journal of clinical investigation. 2012;122(8):2731-40.
4. 4. Akgül AG. Effect of nitric oxide synthase inhibitors in acute lung injury due to blunt lung trauma in rats. Turkish Journal of Thoracic and Cardiovascular Surgery. 2019;27(1).
5. 5. Hoth JJ, Stitzel JD, Gayzik FS, Brownlee NA, Miller PR, Yoza BK, et al. The pathogenesis of pulmonary contusion: an open chest model in the rat. Journal of Trauma and Acute Care Surgery. 2006;61(1):32-45.
6. 6. Miller PR, Croce MA, Bee TK, Qaisi WG, Smith CP, Collins GL, et al. ARDS after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. Journal of Trauma and Acute Care Surgery. 2001;51(2):223-30.
7. 7. Teng D, Pang Q-f, Yan W-j, Xin WZ, Xu C-y. The harmful effect of prolonged high-dose methylprednisolone in acute lung injury. International immunopharmacology. 2013;15(2):223-6.
8. 8. Takıl A, Umuroğlu T, Göğüş YF, Etı Z, Yildizelı B, Ahiskali R. Histopathologic effects of lipid content of enteral solutions after pulmonary aspiration in rats. Nutrition. 2003;19(7-8):666-9.

9. 9. Lee CG, Da Silva CA, Dela Cruz CS, Ahangari F, Ma B, Kang M-J, et al. Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury. Annual review of physiology. 2011;73:479-501.
10. 10. Johansen J, Pedersen AN, Schroll M, Jørgensen T, Pedersen B, Bruunsgaard H. High serum YKL‐40 level in a cohort of octogenarians is associated with increased risk of all‐cause mortality. Clinical & Experimental Immunology. 2008;151(2):260-6.
11. 11. Rathcke CN, Raymond I, Kistorp C, Hildebrandt P, Faber J, Vestergaard H. Low grade inflammation as measured by levels of YKL-40: association with an increased overall and cardiovascular mortality rate in an elderly population. International journal of cardiology. 2010;143(1):35-42.
12. 12. Watanabe T, Akishita M, Toba K, Kozaki K, Eto M, Sugimoto N, et al. Influence of sex and age on serum nitrite/nitrate concentration in healthy subjects. Clinica chimica acta. 2000;301(1-2):169-79.
13. 13. Žunić G, Čolić M, Vučeljić M. Nitrite to nitrate molar ratio is inversely proportional to oxidative cell damages and granulocytic apoptosis at the wound site following cutaneous injury in rats. Nitric Oxide. 2009;20(4):264-9.
14. 14. Cadenas E, Packer L. Handbook of antioxidants: Marcel Dekker New York; 2002.
15. 15. Kumar V, Abbas AK, Aster JC. Robbins basic pathology e-book: Elsevier Health Sciences; 2017.
16. 16. Davies KJ, editor Oxidative stress: the paradox of aerobic life. Biochemical Society Symposia; 1995: Portland Press Limited.
17. 17. Puntel RL, Nogueira CW, Rocha JB. Krebs cycle intermediates modulate thiobarbituric acid reactive species (TBARS) production in rat brain in vitro. Neurochemical research. 2005;30(2):225-35.
18. 18. Franz J, Richardson J, Grover F, Trinkle J. Effect of methylprednisolone sodium succinate on experimental pulmonary contusion. The Journal of thoracic and cardiovascular surgery. 1974;68(5):842-4.
19. 19. Svennevig JL, Pillgram-Larsen J, Fjeld NB, Birkeland S, Semb G. Early use of corticosteroids in severe closed chest injuries: a 10-year experience. Injury. 1987;18(5):309-12.
20. 20. Simon B, Ebert J, Bokhari F, Capella J, Emhoff T, Hayward III T, et al. Management of pulmonary contusion and flail chest: an Eastern Association for the Surgery of Trauma practice management guideline. Journal of Trauma and Acute Care Surgery. 2012;73(5):S351-S61.