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Article

Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury

  • Authors:
    • Zeynep Berna Aksakalli-Magden
    • Rustem Anil Ugan
    • Erdem Toktay
    • Zekai Halici
    • Elif Cadirci
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey, Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240 Erzurum, Turkey, Department of Histology and Embryology, Faculty of Medicine, Kafkas University, 36100 Kars, Turkey
  • Article Number: 66
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    Published online on: December 12, 2022
       https://doi.org/10.3892/etm.2022.11765
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Abstract

The renin‑angiotensin‑aldosterone system (RAAS) is an important pathway that contributes to the pathophysiology of acute liver injury due to paracetamol toxicity. Omapatrilat, a RAAS‑acting agent, inhibits both angiotensin converting enzyme (ACE) and neprilysin/neutral endopeptidase (NEP). The aim of the present study was to investigate the hepatoprotective effects of omapatrilat and examine the role of ACE/NEP pathway on the physiopathology of paracetamol toxicity. A total of 56 BALB/c mice were separated into seven groups: Control, 40 mg/kg omapatrilat only, 400 mg/kg paracetamol only, paracetamol and 140 mg/kg N‑acetylcysteine and three groups with paracetamol and 10‑40 mg/kg omapatrilat. Blood and liver tissue samples were studied through histopathological imaging, alanine transaminase (ALT) and aspartate transaminase (AST) liver function tests and oxidant/antioxidant biomarker measurements including superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). ACE and NEP activities were also measured. Histopathological analysis revealed that paracetamol toxicity resulted in a number of apoptotic and necrotic cells in liver tissue samples. By contrast, with 40 mg/kg omapatrilat administration in toxicity‑induced mice, hepatocytes were significantly improved and exhibited similar appearance to the control group. Biochemical measurements also supported these histopathological results. Omapatrilat pretreatment provided a dose‑dependent reduction in oxidative stress and reversed paracetamol toxicity indications by reducing ALT and AST activities, increasing SOD activity and GSH levels and reducing MDA levels. Dose‑dependent increase of ACE and NEP enzymes in omapatrilat groups was also observed. The results demonstrated promotion of antioxidant activity by omapatrilat and suppression of oxidative stress associated with acute liver injury. These findings revealed the potential role of ACE/NEP pathway in paracetamol toxicity and hepatoprotective effects of omapatrilat against oxidative stress.
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Copy and paste a formatted citation
Spandidos Publications style
Aksakalli-Magden ZB, Ugan RA, Toktay E, Halici Z and Cadirci E: Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Exp Ther Med 25: 66, 2023.
APA
Aksakalli-Magden, Z.B., Ugan, R.A., Toktay, E., Halici, Z., & Cadirci, E. (2023). Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Experimental and Therapeutic Medicine, 25, 66. https://doi.org/10.3892/etm.2022.11765
MLA
Aksakalli-Magden, Z. B., Ugan, R. A., Toktay, E., Halici, Z., Cadirci, E."Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury". Experimental and Therapeutic Medicine 25.1 (2023): 66.
Chicago
Aksakalli-Magden, Z. B., Ugan, R. A., Toktay, E., Halici, Z., Cadirci, E."Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury". Experimental and Therapeutic Medicine 25, no. 1 (2023): 66. https://doi.org/10.3892/etm.2022.11765
Copy and paste a formatted citation
x
Spandidos Publications style
Aksakalli-Magden ZB, Ugan RA, Toktay E, Halici Z and Cadirci E: Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Exp Ther Med 25: 66, 2023.
APA
Aksakalli-Magden, Z.B., Ugan, R.A., Toktay, E., Halici, Z., & Cadirci, E. (2023). Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury. Experimental and Therapeutic Medicine, 25, 66. https://doi.org/10.3892/etm.2022.11765
MLA
Aksakalli-Magden, Z. B., Ugan, R. A., Toktay, E., Halici, Z., Cadirci, E."Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury". Experimental and Therapeutic Medicine 25.1 (2023): 66.
Chicago
Aksakalli-Magden, Z. B., Ugan, R. A., Toktay, E., Halici, Z., Cadirci, E."Potential role of angiotensin converting enzyme/neprilysin pathway and protective effects of omapatrilat for paracetamol‑induced acute liver injury". Experimental and Therapeutic Medicine 25, no. 1 (2023): 66. https://doi.org/10.3892/etm.2022.11765
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