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Inhibiting poly (ADP-ribose) polymerase 1 activation alleviates acetaminophen-induced acute liver injury in mice

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Abstract

Background

Acetaminophen (APAP) overdose can cause severe acute liver injury. Poly (ADP-ribose) polymerase 1 (PARP1) is a nuclear protease that senses DNA breaks and repairs damaged DNA. The role PARP1 plays in APAP-induced hepatotoxicity is still unclear.

Materials and methods

The study was designed in two parts. First, the relationship between PARP1 expression and hepatotoxicity was investigated. Then, the inhibitor PJ34 was used to inhibit the activity of PARP1 and examined its effects. In particular, APAP, vehicle or PJ34 was intraperitoneally administered to mice. Serum transaminase levels were measured with commercial kits. Hematoxylin & eosin staining was used for histopathological observation of the liver. The protein levels of PARP1, poly (ADP-ribose), Sirtuin1 (Sirt1) and γ-H2AX were detected by western blotting.

Results

In a dose- and time-dependent manner, APAP exposure resulted in the overactivation of PARP1 in the livers of mice. Posttreatment with PJ34 ameliorated changes in serum transaminase levels, and histopathological abnormalities. The protein expression of Sirt1 was elevated by PJ34, while that of PARP1, poly (ADP-ribose), and γ-H2AX was reduced due to PJ34 administration.

Conclusion

Excessive APAP administration results in PARP1 overactivation, and its inhibition sheds light on the treatment of APAP-induced liver injury.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

The authors thank the Chongqing Yike Tianya Biotechnology Co., Ltd for the assistance in H&E and PAS staining.

Funding

This work was supported by the program for Youth Innovation in Future Medicine from Chongqing Medical University (Grant No. W0057).

Author information

Author notes

  1. Jiarui Tang and Cuiting Liao have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathophysiology, School of Basic Medical College, Chongqing Medical University, 1 Yixueyuan Road, Chongqing, 400016, China

    Jiarui Tang, Cuiting Liao, Yongqiang Yang, Jiayi Huang, Li Tang, Li Zhang & Longjiang Li

  2. Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, 400016, China

    Jiarui Tang, Cuiting Liao, Kai Hu, Yongqiang Yang, Jiayi Huang, Li Tang, Li Zhang & Longjiang Li

  3. Center of Health Management, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400000, China

    Longhui Li

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  1. Jiarui Tang
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Contributions

LL designed the research study. JT and CL conducted the experiments, acquired data and wrote the manuscript. KH, LL and YY revised the manuscript and corrected the figure results. JH and LT analyzed the data. LZ provided reagents. All the authors participated in manuscript preparation and approved the final manuscript. JT and CL contributed equally to this work.

Corresponding authors

Correspondence to Li Zhang or Longjiang Li.

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Conflict of interest

Jiarui Tang declares that she has no conflicts of interest. Cuiting Liao declares that she has no conflicts of interest. Kai Hu declares that he has no conflicts of interest. Longhui Li declares that she has no conflicts of interest. Yongqiang Yang declares that he has no conflicts of interest. Jiayi Huang declares that she has no conflicts of interest. Li Tang declares that she has no conflicts of interest. Li Zhang declares that he has no conflicts of interest. Longjiang Li declares that he has no conflicts of interest.

Ethics approval

The Chongqing Medical University Committee approved all experimental procedures.

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Tang, J., Liao, C., Hu, K. et al. Inhibiting poly (ADP-ribose) polymerase 1 activation alleviates acetaminophen-induced acute liver injury in mice. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00400-y

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