The Protective Effect of Ethyl Pyruvate on Liver Injury in Rats with Hemorrhagic Shock and Its Potential Mechanisms
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i3.4430
Abstract
To investigate the protective effects and underlying mechanisms of ethyl pyruvate (EP) on acute liver injury induced by hemorrhagic shock in rats. An acute liver injury model induced by hemorrhagic shock in rats was established. The intervention was performed with EP, an HMGB1 release inhibitor, to observe its protective effects on this injury. Thirty-two male Wistar rats were randomly divided into four groups: normal control group (Normal group, N=8), hemorrhagic shock group (Shock group, N=8), hemorrhagic shock and resuscitation control group (Shock+actated Ringer's solution group, N=8), and EP intervention group (Shock+EP intervention group, N=8). Rats that died during the experiment were immediately dissected, and their livers were collected. Venous blood samples were collected at 1 hour, 6 hours, and 12 hours after resuscitation. After 12 hours of resuscitation, rats were euthanized, and their livers were collected. Levels of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in rat serum were determined using an automatic biochemical analyzer. Liver specimens were stained with hematoxylin-eosin (HE) for pathological examination. The levels of acetylated high mobility group protein B1 (AC-HMGB1), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and the activity of superoxide dismutase (SOD) in liver tissues were detected using ELISA. Compared with the normal control group, rats in the hemorrhagic shock group exhibited significantly elevated levels of TBIL, DBIL, ALT, and ALP in serum (p<0.05). Liver tissues showed extensive infiltration of inflammatory cells and localized hemorrhagic necrosis. Expression of AC-HMGB1, IL-6, TNF-α, and MDA in liver tissues was significantly increased (P<0.05), while SOD was significantly decreased (p<0.05). Compared with the hemorrhagic shock group, rats in the EP intervention group showed significantly decreased levels of TBIL, DBIL, ALT, and ALP in serum (p<0.05), along with improved pathological changes in liver tissues. Additionally, expression of AC-HMGB1, IL-6, TNF-α, and MDA in liver tissues was significantly reduced (p<0.05), while SOD was significantly increased (p<0.05). EP effectively ameliorates acute liver injury in rats induced by hemorrhagic shock, potentially through its inhibition of inflammatory response, antioxidant properties, and reduction of AC-HMGB1 expression in liver tissues.
Keywords
Hemorrhagic Shock; Acute Liver Injury; Ethyl Pyruvate (EP); HMGB1
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[7] Wang, Y., Le, Y., Wu, J., Zhao, W., Zhang, Q., Xu, G.(2024). Inhibition of xanthine oxidase by allopurinol suppresses HMGB1 secretion and ameliorates experimental asthma. Redox Biol. 70:103021.
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[14] Kim, Y. M., Park, E. J., Kim, J. H., Park, S. W., Kim, H. J., & Chang, K. C.(2016). Ethyl pyruvate inhibits the acetylation and release of HMGB1 via effects on SIRT1/STAT signaling in LPS-activated RAW264.7 cells and peritoneal macrophages[J].Int Immunopharmacol,41(11):98-105.
[15] Karki, R., Sharma, B. R., Tuladhar, S., Williams, E. P., Zalduondo, L., & Samir, P. (2021). Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 184(1):149-168.
[16] Cao Y, Liu M, Wu S, Xu J, Wang W, Qi X(2022). Kupffer cells play a crucial role in monocrotaline- induced liver injury by producing TNF-α. Toxicology. 468:153101.
[17] Wang Y, Zhang H, Chen Q, Jiao F, Shi C, Pei M(2020). TNF-α/HMGB1 inflammation signalling pathway regulates pyroptosis during liver failure and acute kidney injury. Cell Prolif. 53(6):e12829.
[18] Wang L, Liu SL, Xu ZP, Song Q, Li L, Qiu ZL(2021). Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock. Open Life Sci. 16(1):1122-1129.
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