LP342, a novel histone deacetylase inhibitor, decreases nitro-oxidative stress, mitochondrial dysfunction and hepatic ischaemia/reperfusion injury in mice.

ABSTRACT:

Objectives

Some histone deacetylase (HDAC) isoforms contribute to ischaemia/reperfusion (IR) injury (IRI). Here, we examined whether LP342, the lead candidate of a new generation of hydrazide-based HDAC inhibitors (HDACi), decreases hepatic IRI.

Methods

IR was induced by clamping blood vessels to ~70% of the livers of mice for 1 h.

Key findings

At 6 h after reperfusion, ALT markedly increased, and wide-spread necrosis, leukocyte infiltration, and apoptosis occurred. LP342 treatment (1 mg/kg, ip) at 20 h or 1 h before ischaemia markedly decreased IRI whereas LP342 treatment upon reperfusion was marginally protective. Nitro-oxidative stress, c-Jun-N-terminal kinase (JNK) activation, and mitochondrial dysfunction contribute to IRI. 4-Hydroxynonenal, 3-nitrotyrosin

SUBMITTER: Samuvel DJ 

PROVIDER: S-EPMC10114105 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature