Granisetron attenuates liver injury and inflammation in a rat model of cecal ligation and puncture-induced sepsis

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.

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Protective Role of Coenzyme Q10 in Acute Sepsis-Induced Liver Injury in BALB/c Mice

BioMed Research International ◽

10.1155/2020/7598375 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qian-wei Li ◽

Qin Yang ◽

Hong-Yang Liu ◽

Yu-ling Wu ◽

Yu-Hua Hao ◽

...

Keyword(s):

Liver Injury ◽

Coenzyme Q10 ◽

Cecal Ligation ◽

Protective Role ◽

Hepatic Tissue ◽

Control Group ◽

Cecal Ligation And Puncture ◽

Sequestosome 1

Sepsis increases the risk of the liver injury development. According to the research works, coenzyme Q10 exhibits hepatoprotective properties in vivo as well as in vitro. Current work aimed at investigating the protective impacts of coenzyme Q10 against liver injury in septic BALB/c mice. The male BALB/c mice were randomly segregated into 4 groups: the control group, the coenzyme Q10 treatment group, the puncture and cecal ligation group, and the coenzyme Q10+cecal ligation and puncture group. Cecal ligation and puncture was conducted after gavagaging the mice with coenzyme Q10 during two weeks. Following 48 h postcecal ligation and puncture, we estimated hepatic biochemical parameters and histopathological changes in hepatic tissue. We evaluated the expression of factors associated with autophagy, pyroptosis, and inflammation. Findings indicated that coenzyme Q10 decreased the plasma levels in alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase in the cecal ligation and puncture group. Coenzyme Q10 significantly inhibited the elevation of sequestosome-1, interleukin-1β, oligomerization domain-like receptor 3 and nucleotide-binding, interleukin-6, and tumor necrosis factor-α expression levels; coenzyme Q10 also increased beclin 1 levels. Coenzyme Q10 might be a significant agent in the treatment of liver injury induced by sepsis.

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Necrostatin-1 accelerates time to death in a rat model of cecal ligation and puncture and massively increases hepatocyte caspase-3 cleavage

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00175.2018 ◽

2019 ◽

Vol 316 (4) ◽

pp. G551-G561 ◽

Cited By ~ 3

Author(s):

Qin Zhang ◽

Siwei Wei ◽

Jiayin Lu ◽

Weijun Fu ◽

Hui Chen ◽

...

Keyword(s):

Protein Kinase ◽

Liver Injury ◽

Survival Time ◽

Caspase 3 ◽

Cecal Ligation ◽

B Cell Lymphoma ◽

Cecal Ligation And Puncture ◽

Interacting Protein ◽

Regulated Necrosis ◽

Related Proteins

Necroptosis, a form of regulated necrosis, has been reported to be involved in numerous pathologies, including sepsis. However, a protective effect of the selective inhibitor of necroptosis, necrostatin-1 (Nec-1), against sepsis remains to be confirmed. Animals (rats and mice) were subjected to cecal ligation and puncture (CLP) to mimic clinical sepsis. Nec-1 or its vehicle (control) was administered 20 min before CLP. Survival time was observed up to 72 h after CLP. Specimens of liver tissue and serum were obtained at 6 h, 12 h, and 18 h. Expression of necroptosis-related proteins [receptor-interacting protein kinase (RIP)1, RIP3, and mixed lineage kinase domain-like (MLKL)] was determined by Western blot analysis. The RIP1/RIP3 interaction and the recruitment of MLKL to RIP3 were also analyzed. Liver function, histopathological changes, serum inflammation cytokines, TUNEL staining, and the expression of apoptosis-related protein, including caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (Bax), was determined. As expected, Nec-1 administration reduced the expression of necroptosis-related proteins and the RIP1/RIP3 interaction, indicating inhibited necroptosis. Surprisingly, Nec-1 treatment exacerbated the liver injury and shortened survival time of septic rats with increased TUNEL-positive cells, cleaved caspase-3 protein content, and Bax/Bcl-2 ratio. Collectively, these findings show that Nec-1 administration inhibited the hepatocyte necroptosis pathway but accelerated apoptosis via the apoptotic pathway in CLP-induced sepsis rat. NEW & NOTEWORTHY The present study demonstrated that a chemical inhibitor necrostatin-1 (Nec-1) or receptor-interacting protein kinase(RIP1) knock down targeted at necroptosis inhibition accelerated liver injury of following sepsis. For fundamental research, these results warrant further investigation of the potential link between Nec-1 administration and the cellular apoptosis following sepsis induced liver injury. For applied research, these results suggest the potential harmful effect of Nec-1 on future sepsis treatment.

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CD123 thioaptamer protects against sepsis via the blockade between IL-3/CD123 in a cecal ligation and puncture rat model

Nucleosides Nucleotides & Nucleic Acids ◽

10.1080/15257770.2020.1815770 ◽

2020 ◽

Vol 40 (1) ◽

pp. 16-31

Author(s):

Jiangang Zhao ◽

Meng Wang ◽

Ying Yang ◽

Guoxia Wang ◽

Fengyu Che ◽

...

Keyword(s):

Rat Model ◽

Cecal Ligation ◽

Cecal Ligation And Puncture

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Sodium Butyrate Ameliorates Intestinal Injury and Improves Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis

Inflammation ◽

10.1007/s10753-019-00987-2 ◽

2019 ◽

Vol 42 (4) ◽

pp. 1276-1286 ◽

Cited By ~ 7

Author(s):

Jiahong Fu ◽

Guofu Li ◽

Xingmao Wu ◽

Bin Zang

Keyword(s):

Sodium Butyrate ◽

Rat Model ◽

Cecal Ligation ◽

Intestinal Injury ◽

Cecal Ligation And Puncture

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Changes of lymph metabolites in a rat model of sepsis induced by cecal ligation and puncture

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e31826fc9e7 ◽

2012 ◽

Vol 73 (6) ◽

pp. 1545-1552 ◽

Cited By ~ 4

Author(s):

Yan Li ◽

Ming Hou ◽

Jian-guang Wang ◽

Tao Wang ◽

Jian Wan ◽

...

Keyword(s):

Rat Model ◽

Cecal Ligation ◽

Cecal Ligation And Puncture

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Liver X Receptor Protects against Liver Injury in Sepsis Caused by Rodent Cecal Ligation and Puncture

Surgical Infections ◽

10.1089/sur.2010.066 ◽

2011 ◽

Vol 12 (4) ◽

pp. 283-289 ◽

Cited By ~ 11

Author(s):

Yun Yong Wang ◽

Una Ryg ◽

Maria K. Dahle ◽

Knut R. Steffensen ◽

Christoph Thiemermann ◽

...

Keyword(s):

Liver Injury ◽

Cecal Ligation ◽

Liver X Receptor ◽

Cecal Ligation And Puncture

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PD-L1 Blockade Attenuated Sepsis-Induced Liver Injury in a Mouse Cecal Ligation and Puncture Model

Mediators of Inflammation ◽

10.1155/2013/361501 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 19

Author(s):

Weimin Zhu ◽

Rui Bao ◽

Xiaohua Fan ◽

Tianzhu Tao ◽

Jiali Zhu ◽

...

Keyword(s):

Liver Injury ◽

Acute Phase Proteins ◽

Therapeutic Potential ◽

Cecal Ligation ◽

Cecal Ligation And Puncture ◽

Host Immune Responses ◽

Programmed Death ◽

Programmed Death 1 ◽

Puncture Model

Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis.

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