Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression

Chen, Zhixia; Chen, Yihui; Jin, Xianwei; Liu, Ying; Shao, Zhongcai; Quan, Li

doi:10.1177/15353702211015620

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Liver injury scoring was performed as previously described 43 : inflammation, edema, haemorrhage and tissue necrosis, with scores of 0, 1, 2, 3 and 4 for each parameter as none, minimal, mild, moderate and severe, respectively.…”

Section: Hematoxylin and Eosin Stainingmentioning

confidence: 99%

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1

Li,

Xuan,

et al. 2023

Clin Exp Pharma Physio

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Sepsis and septic shock are common critical illnesses in the intensive care unit with a high mortality rate. Geldanamycin (GA) has a broad spectrum of antibacterial and antiviral activity and has inhibitory effects on various viruses. However, whether GA affects sepsis due to infections remains unknown. In this study, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine in serum; neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 in the urine, cytokines (tumour necrosis factor alpha, interleukin‐1β and interleukin‐6) in the bronchoalveolar lavage fluid and myeloperoxidase in the lung tissues were measured using enzyme‐linked immunosorbent assay kits. Pathological injury was measured by hematoxylin and eosin staining and neutrophils were measured by flow cytometry analysis; related expressions were analysed by qPCR, western blot and immunofluorescence assay. The results showed that GA significantly ameliorated cecum ligation and puncture (CLP)‐triggered liver, kidney and lung injury in septic mice. In addition, we found that GA dose‐dependently inhibited microthrombosis and alleviated coagulopathy in septic mice. Further molecular mechanism analysis suggests that GA may act through upregulation of heat shock factor 1 and tissue‐type plasminogen activator. In conclusion, our study elucidated the protective effects of GA in a mouse model established using CLP, and the results reveal that GA may be a promising agent for sepsis.

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Section: Hematoxylin and Eosin Stainingmentioning

confidence: 99%

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1

Li,

Xuan,

et al. 2023

Clin Exp Pharma Physio

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“… 2017 ; Chen et al. 2021 ). The findings of current study indicated that the secretion of cTnI, CK, CK-MB, Cr, BUN, ALT, and AST induced by CLP treatment could be reversed by parenteral ω-3 PUFAs solutions treatment, suggesting the protective role of ω-3 PUFA solutions in sepsis induced multi-organ injury.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

Liu

et al. 2023

Pharmaceutical Biology

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Context Sepsis is a systemic inflammatory response caused by infection, with high morbidity and mortality. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have reported biological activities. Objective This study explored the signaling pathways through which ω-3 PUFAs protect against sepsis-induced multiorgan failure. Materials and methods Septic Sprague-Dawley (SD) rat model was established by the cecum ligation perforation (CLP) method. Rats were divided into control, sham, model, parenteral ω-3 PUFAs (0.5 g/kg) treatment, ω-3 PUFAs (0.5 g/kg) + AMPK inhibitor Compound C (30 mg/kg) treatment, and ω-3 PUFAs (0.5 g/kg) + mTOR activator MHY1485 (10 mg/kg) treatment groups. The serum inflammatory cytokines were measured using ELISA. Organ damage-related markers cTnI, CK, CK-MB, Cr, BUN, ALT, and AST were measured using an automated chemical analyzer. The AMPK/mTOR pathway in liver, kidney, and myocardial tissues was detected using western blot and qRT-PCR methods. Results CLP treatment enhanced the secretion of pro-inflammatory cytokines and multi-organ related markers, along with increased p-AMPK/AMPK ratio (from 0.47 to 0.87) and decreased p-mTOR/mTOR ratio (from 0.33 to 0.12) in rats. The inflammation response and multi-organ injury induced by CLP treatment could be partially counteracted by 0.5 g/kg parenteral ω-3 PUFA treatment. The activated AMPK/mTOR pathway in CLP-induced rats was further promoted. Finally, Compound C and MHY1485 could reverse the effects of parenteral ω-3 PUFA treatment on sepsis rats. Discussion and conclusion ω-3 PUFAs ameliorated sepsis development by activating the AMPK/mTOR pathway, serving as a potent therapeutic agent for sepsis. Further in vivo studies may validate potential clinical use.

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Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux

Liu,

Li,

Hao

et al. 2024

Pharmacological Research

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Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression

Cited by 3 publications

References 41 publications

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1

Geldanamycin ameliorates multiple organ dysfunction and microthrombosis in septic mice by inhibiting the formation of the neutrophil extracellular network by activating heat shock factor 1 HSF1

Protective effect of omega-3 polyunsaturated fatty acids on sepsis via the AMPK/mTOR pathway

Low-dose Olaparib improves septic cardiac function by reducing ferroptosis via accelerated mitophagy flux

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