Inhibition of Drug-Induced Liver Injury in Mice Using a Positively Charged Peptide That Binds DNA.

ABSTRACT: Hepatic cell death occurs in response to diverse stimuli such as chemical and physical damage. The exposure of intracellular contents such as DNA during necrosis induces a severe inflammatory response that has yet to be fully explored therapeutically. Here, we sought means to neutralize the ability of extracellular DNA to induce deleterious tissue inflammation when drug-induced liver injury had already ensued. DNA exposure and inflammation were investigated in vivo in drug-induced liver injury using intravital microscopy. The necrotic DNA debris was studied in murine livers in vivo and in DNA debris models in vitro by using a positively charged chemokine-derived peptide (MIG30; CXCL9[74-103]). Acetaminophen-induced liver necrosis was associated with massive DNA accumulation, production of

SUBMITTER: Marques PE 

PROVIDER: S-EPMC8485890 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature