Having previously demonstrated that endogenous phosphatidic acid (PA) promotes liver regeneration after acetaminophen (APAP) hepatotoxicity, the authors of this paper hypothesize that exogenous PA is also beneficial. To test that, the authors treated mice with a toxic APAP dose at 0 h, followed by PA or vehicle (Veh) post-treatment. Blood and liver were then collected at 6, 24, and 52 h. Post-treatment with PA 2 h after APAP protected against liver injury at 6 h, and the combination of PA and N -acetyl-L-cysteine (NAC) reduced injury more than NAC alone. PA did not affect canonical mechanisms of APAP toxicity. Instead, transcriptomics revealed that PA activated interleukin-6 (IL-6) signaling in the liver. Consistent with that, serum IL-6 and hepatic signal transducer and activator of transcription 3 (Stat3) phosphorylation increased in PA-treated mice. Furthermore, PA failed to protect against APAP in IL-6-deficient animals. IL-6 expression increased 18-fold in adipose tissue after PA, indicating that adipose is a source of PA-induced circulating IL-6. However, exogenous PA did not alter regeneration, despite the importance of endogenous PA in liver repair, possibly due to its short half-life.
With these data the authors demonstrate that exogenous PA is also beneficial in APAP toxicity and reinforces the protective effects of IL-6 in this model.
Article reference: Clemens MM, Kennon-McGill S, Vazquez JH, Stephens OW, PetersonEA, Johann DJ, Allard FD, Yee EU, McCullough SS, James LP, Finck BN, McGill MR, Exogenousphosphatidic acid reduces acetaminophen-induced liver injury in mice by activating hepatic interleukin-6 signaling through inter-organ crosstalk, Acta Pharmaceutica Sinica B , 2021, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2021.08.024
Keywords: Acute liver injury; Acute liver failure; Adipokine; Cytokine; Dietary supplement; Drug-induced liver injury; Hepatotoxicity; Lipid
# # # # # #
https://doi.org/10.1016/j.apsb.2021.08.024
The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association .
For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/
Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board
APSB is available on ScienceDirect ( https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b ).
Submissions to APSB may be made using Editorial Manager ® ( https://www.editorialmanager.com/apsb/default.aspx ).
CiteScore: 12.5
Impact Factor: 11.614
JIF without self-citation: 10.746
ISSN 2211-3835
Acta Pharmaceutica Sinica B