Effects of hypothermia on inflammatory cytokine expression in rat liver following asphyxial cardiac arrest

Park,Yoonsoo; Ahn,Ji Hyeon; Cho,Jeong Hwi; Tae,Hyun-Jin; Lee,Tae-Kyeong; Kim,Bora; Lee,Jae-Chul; Park,Joon Ha; Shin,Myoung Cheol; Ohk,Taek Geun; Cho,Jun Hwi; Won,Moo-Ho

doi:10.3892/etm.2021.10058

Effects of hypothermia on inflammatory cytokine expression in rat liver following asphyxial cardiac arrest

Authors:
- Yoonsoo Park
- Ji Hyeon Ahn
- Jeong Hwi Cho
- Hyun-Jin Tae
- Tae-Kyeong Lee
- Bora Kim
- Jae-Chul Lee
- Joon Ha Park
- Myoung Cheol Shin
- Taek Geun Ohk
- Jun Hwi Cho
- Moo-Ho Won
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Affiliations: Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea, Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan, Gyeongnam 50510, Republic of Korea, Bio‑Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeollabuk 54596, Republic of Korea, Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea, Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea, Department of Anatomy, College of Korean Medicine, Dongguk University, Gyeongju, Gyeongbuk 38066, Republic of Korea
Published online on: April 15, 2021 https://doi.org/10.3892/etm.2021.10058
Article Number: 626
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hypothermic treatment is known to protect against cardiac arrest (CA) and improve survival rate. However, few studies have evaluated the CA‑induced liver damage and the effects of hypothermia on this damage. Therefore, the aim of the present study was to determine possible protective effects of hypothermia on the liver after asphyxial CA. Rats were subjected to a 5‑min asphyxial CA followed by return of spontaneous circulation (ROSC). The body temperature was controlled at 37±0.5˚C (normothermia group) or 33±0.5˚C (hypothermia group) for 4 h after ROSC. Livers were examined at 6, 12 h, 1 and 2 days after ROSC. Histopathological examination was performed by H&E staining. Alterations in the expression levels of pro‑inflammatory (TNF‑α and interleukin IL‑2) and anti‑inflammatory cytokines (IL‑4 and IL‑13) were investigated by immunohistochemistry. Sinusoidal dilatation and vacuolization were observed after asphyxial CA by histopathological examination. However, these CA‑induced structural alterations were prevented by hypothermia. In immunohistochemical examination, the expression levels of pro‑inflammatory cytokines were reduced in the hypothermia group compared with those in the normothermia group while the expression levels of anti‑inflammatory cytokines were increased in the hypothermia group compared with those in the normothermia group. In conclusion, hypothermic treatment for 4 h following asphyxial CA in rats inhibited the increase of pro‑inflammatory cytokines and stimulated the expression of anti‑inflammatory cytokines compared with the normothermic group. The results of the present study suggested that hypothermic treatment after asphyxial CA reduced liver damage via the regulation of inflammation.

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1	Kato A, Okaya T and Lentsch AB: Endogenous IL-13 protects hepatocytes and vascular endothelial cells during ischemia/reperfusion injury. Hepatology. 37:304–312. 2003.PubMed/NCBI View Article : Google Scholar
2	Shuh M, Bohorquez H, Loss GE Jr and Cohen AJ: Tumor necrosis factor-α: Life and death of hepatocytes during liver ischemia/reperfusion injury. Ochsner J. 13:119–130. 2013.PubMed/NCBI
3	Carr BG, Kahn JM, Merchant RM, Kramer AA and Neumar RW: Inter-hospital variability in post-cardiac arrest mortality. Resuscitation. 80:30–34. 2009.PubMed/NCBI View Article : Google Scholar
4	Kida K, Shirozu K, Yu B, Mandeville JB, Bloch KD and Ichinose F: Beneficial effects of nitric oxide on outcomes after cardiac arrest and cardiopulmonary resuscitation in hypothermia-treated mice. Anesthesiology. 120:880–889. 2014.PubMed/NCBI View Article : Google Scholar
5	Miao YF, Wu H, Yang SF, Dai J, Qiu YM, Tao ZY and Zhang XH: 5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response. Mediators Inflamm. 2015(520745)2015.PubMed/NCBI View Article : Google Scholar
6	Niemann CU, Feiner J, Swain S, Bunting S, Friedman M, Crutchfield M, Broglio K, Hirose R, Roberts JP and Malinoski D: Therapeutic hypothermia in deceased organ donors and kidney-graft function. N Engl J Med. 373:405–414. 2015.PubMed/NCBI View Article : Google Scholar
7	Niemann CU, Xu F, Choi S, Behrends M, Park Y, Hirose R and Maher JJ: Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines. J Surg Res. 158:43–52. 2010.PubMed/NCBI View Article : Google Scholar
8	Abu-Amara M, Yang SY, Tapuria N, Fuller B, Davidson B and Seifalian A: Liver ischemia/reperfusion injury: Processes in inflammatory networks-a review. Liver Transpl. 16:1016–1032. 2010.PubMed/NCBI View Article : Google Scholar
9	Eltzschig HK and Eckle T: Ischemia and reperfusion-from mechanism to translation. Nat Med. 17:1391–1401. 2011.PubMed/NCBI View Article : Google Scholar
10	Lentsch AB, Kato A, Yoshidome H, McMasters KM and Edwards MJ: Inflammatory mechanisms and therapeutic strategies for warm hepatic ischemia/reperfusion injury. Hepatology. 32:169–173. 2000.PubMed/NCBI View Article : Google Scholar
11	Jaeschke H, Bautista AP, Spolarics Z and Spitzer JJ: Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia. Free Radic Res Commun. 15:277–284. 1991.PubMed/NCBI View Article : Google Scholar
12	Jaeschke H, Farhood A and Smith C: Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo. FASEB J. 4:3355–3359. 1990.PubMed/NCBI
13	Black PR, van Devanter S and Cohn LH: Effects of hypothermia on systemic and organ system metabolism and function. J Surg Res. 20:49–63. 1976.PubMed/NCBI View Article : Google Scholar
14	Xiao Q, Ye Q, Wang W, Xiao J, Fu B, Xia Z, Zhang X, Liu Z and Zeng X: Mild hypothermia pretreatment protects against liver ischemia reperfusion injury via the PI3K/AKT/FOXO3a pathway. Mol Med Rep. 16:7520–7526. 2017.PubMed/NCBI View Article : Google Scholar
15	Abdo EE, Figueira ER, Rocha-Filho JA, Chaib E, D'Albuquerque LA and Bacchella T: Preliminary results of topical hepatic hypothermia in a model of liver ischemia/reperfusion injury in rats. Arq Gastroenterol. 54:246–249. 2017.PubMed/NCBI View Article : Google Scholar
16	Behrends M, Hirose R, Serkova NJ, Coatney JL, Bedolli M, Yardi J, Park YH and Niemann CU: Mild hypothermia reduces the inflammatory response and hepatic ischemia/reperfusion injury in rats. Liver Int. 26:734–741. 2006.PubMed/NCBI View Article : Google Scholar
17	Eum HA, Cha YN and Lee SM: Necrosis and apoptosis: Sequence of liver damage following reperfusion after 60 min ischemia in rats. Biochem Biophys Res Commun. 358:500–505. 2007.PubMed/NCBI View Article : Google Scholar
18	Lee JC, Tae HJ, Cho JH, Kim IS, Lee TK, Park CW, Park YE, Ahn JH, Park JH, Yan BC, et al: Therapeutic hypothermia attenuates paraplegia and neuronal damage in the lumbar spinal cord in a rat model of asphyxial cardiac arrest. J Therm Biol. 83:1–7. 2019.PubMed/NCBI View Article : Google Scholar
19	Ahn JH, Lee TK, Kim B, Lee JC, Tae HJ, Cho JH, Park Y, Shin MC, Ohk TG, Park CW, et al: Therapeutic hypothermia improves hind limb motor outcome and attenuates oxidative stress and neuronal damage in the lumbar spinal cord following cardiac arrest. Antioxidants (Basel). 9(38)2020.PubMed/NCBI View Article : Google Scholar
20	Kim YS, Cho JH, Shin MC, Park Y, Park CW, Tae HJ, Cho JH, Kim IS, Lee TK, Park YE, et al: Effects of regional body temperature variation during asphyxial cardiac arrest on mortality and brain damage in a rat model. J Therm Biol. 87(102466)2020.PubMed/NCBI View Article : Google Scholar
21	Cho JH, Tae HJ, Kim IS, Song M, Kim H, Lee TK, Kim YM, Ryoo S, Kim DW, Lee CH, et al: Melatonin alleviates asphyxial cardiac arrest-induced cerebellar Purkinje cell death by attenuation of oxidative stress. Exp Neurol. 320(112983)2019.PubMed/NCBI View Article : Google Scholar
22	National Research Council (US): Committee for the Update of the Guide for the Care and Use of Laboratory Animals: Guide for the Care and Use of Laboratory Animals. 8th edition. National Academies Press, Washington, DC, 2010.
23	Leary S, Underwood W, Anthony R, Corey D, Grandin T, Greenacre C, Gwaltney-Brant S, McCrackin MA, Meyer R, Miller D, et al: AVMA guidelines for the euthanasia of animals: 2013 edition. Journal, pp1-102, 2013.
24	Han F, Boller M, Guo W, Merchant RM, Lampe JW, Smith TM and Becker LB: A rodent model of emergency cardiopulmonary bypass resuscitation with different temperatures after asphyxial cardiac arrest. Resuscitation. 81:93–99. 2010.PubMed/NCBI View Article : Google Scholar
25	Drabek T, Foley LM, Janata A, Stezoski J, Hitchens TK, Manole MD and Kochanek PM: Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using ASL-MRI. Resuscitation. 85:964–971. 2014.PubMed/NCBI View Article : Google Scholar
26	Hu T, Wang J, Wang S, Li J, Chen B, Zuo F, Zhang L, Huang Y and Li Y: Effects of the duration of postresuscitation hyperoxic ventilation on neurological outcome and survival in an asphyxial cardiac arrest rat model. Sci Rep. 9(16500)2019.PubMed/NCBI View Article : Google Scholar
27	Jia X, Koenig MA, Shin HC, Zhen G, Pardo CA, Hanley DF, Thakor NV and Geocadin RG: Improving neurological outcomes post-cardiac arrest in a rat model: Immediate hypothermia and quantitative EEG monitoring. Resuscitation. 76:431–442. 2008.PubMed/NCBI View Article : Google Scholar
28	Lee CH, Park JH, Cho JH, Kim IH, Ahn JH, Lee JC, Chen BH, Shin BN, Tae HJ, Bae EJ, et al: Effect of oenanthe javanica extract on antioxidant enzyme in the rat liver. Chin Med J (Engl). 128:1649–1654. 2015.PubMed/NCBI View Article : Google Scholar
29	Carpenter JW: Exotic Animal Formulary. 4th edition. Elsevier Health Sciences, p744, 2012.
30	Park JH, Park O, Cho JH, Chen BH, Kim IH, Ahn JH, Lee JC, Yan BC, Yoo KY, Lee CH, et al: Anti-inflammatory effect of tanshinone I in neuroprotection against cerebral ischemia-reperfusion injury in the gerbil hippocampus. Neurochem Res. 39:1300–1312. 2014.PubMed/NCBI View Article : Google Scholar
31	Nakagawa K, Miller FN, Sims DE, Lentsch AB, Miyazaki M and Edwards MJ: Mechanisms of interleukin-2-induced hepatic toxicity. Cancer Res. 56:507–510. 1996.PubMed/NCBI
32	Strieter RM, Remick DG, Lynch JP III, Spengler RN and Kunkel SL: Interleukin-2-induced tumor necrosis factor-alpha (TNF-alpha) gene expression in human alveolar macrophages and blood monocytes. Am Rev Respir Dis. 139:335–342. 1989.PubMed/NCBI View Article : Google Scholar
33	Li J, Ke W, Zhou Q, Wu Y, Luo H, Zhou H, Yang B, Guo Y, Zheng Q and Zhang Y: Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway. J Cell Mol Med. 18:1863–1873. 2014.PubMed/NCBI View Article : Google Scholar
34	Colletti LM, Remick DG, Burtch GD, Kunkel SL, Strieter RM and Campbell DA Jr: Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat. J Clin Invest. 85:1936–1943. 1990.PubMed/NCBI View Article : Google Scholar
35	Yang YL, Li JP, Xu XP, Dou KF, Yue SQ and Li KZ: Protective effects of tumor necrosis factor alpha antibody and ulinastatin on liver ischemic reperfusion in rats. World J Gastroenterol. 10:3161–3164. 2004.PubMed/NCBI View Article : Google Scholar
36	Kato A, Yoshidome H, Edwards MJ and Lentsch AB: Reduced hepatic ischemia/reperfusion injury by IL-4: Potential anti-inflammatory role of STAT6. Inflamm Res. 49:275–279. 2000.PubMed/NCBI View Article : Google Scholar
37	Cannistrà M, Ruggiero M, Zullo A, Gallelli G, Serafini S, Maria M, Naso A, Grande R, Serra R and Nardo B: Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers. Int J Surg. 33 (Suppl 1):S57–S70. 2016.PubMed/NCBI View Article : Google Scholar
38	Girotra S, Chan PS and Bradley SM: Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart. 101:1943–1949. 2015.PubMed/NCBI View Article : Google Scholar