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Protective effects of BML-111 against acetaminophen-induced acute liver injury in mice

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Abstract

The present study was undertaken to investigate the effect of the new formyl peptide receptor 2/lipoxin A4 receptor agonist BML-111 on acetaminophen (APAP)-induced liver injury in mice and explore its possible mechanism(s). Male Swiss albino mice were intraperitoneally injected with BML-111 (1 mg/kg) twice daily for five consecutive days prior to a single intraperitoneal injection of APAP (500 mg/kg). Results have shown that APAP injection caused liver damage as indicated by significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver histopathological examination revealed marked necrosis and inflammation. Additionally, APAP decreased activities of hepatic glutathione (GSH) and superoxide dismutase (SOD) with significant increase in the hepatic malondialdehyde (MDA) content. Furthermore, APAP increased serum nitrite/nitrate (NO2 −/NO3 − ) level and hepatic tumor necrosis factor alpha (TNF-α). Pretreatment with BML-111 significantly reversed all APAP-induced pathological changes. BML-111 prevented the increase of AST, ALT, and ALP. Also, BML-111 markedly attenuated APAP-induced necrosis and inflammation. It decreased MDA with increase in SOD and GSH. Importantly, BML-111 decreased NO2 −/NO3 − level and TNF-α. These findings suggest that BML-111 has hepatoprotective effects against APAP-induced liver injury in mice. Its protective effect may be attributed to its ability to counteract the inflammatory ROS generation and regulate cytokine effects.

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Abbreviations

APAP:

Acetaminophen

ALT:

Alanine aminotransferase

ALP:

Alkaline phosphatase

AST:

Aspartate aminotransferase

FPR2/ALX:

Formyl peptide receptor 2/lipoxin A4 receptor

GSH:

Reduced glutathione

LX:

Lipoxin

MDA:

Malondialdehyde

NO2 −/NO3 − :

Nitrite/nitrate

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor alpha

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Acknowledgments

The authors acknowledge Dr. Abdelhadi M. Shebl, Department of Pathology, Faculty of Medicine, Mansoura University, for providing assistance.

Conflicts of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    Dina S. El-Agamy, Mirhan N. Makled & Nareman M. Gamil

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  1. Dina S. El-Agamy
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  3. Nareman M. Gamil
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Correspondence to Dina S. El-Agamy.

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El-Agamy, D.S., Makled, M.N. & Gamil, N.M. Protective effects of BML-111 against acetaminophen-induced acute liver injury in mice. J Physiol Biochem 70, 141–149 (2014). https://doi.org/10.1007/s13105-013-0288-x

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