Capsaicin is the main pungent bioactive constituent in red chili with promising therapeutic properties due to its anti-oxidative and anti-inflammatory effects. No evidence exists on the beneficial effect of
capsaicin on apoptosis and mitochondrial function in acute liver injury (ALI) under septic conditions. For inducing septic ALI,
lipopolysaccharide (LPS, 50 μg/kg) and
d-galactose (D-Gal, 400 mg/kg) was intraperitoneally injected and
capsaicin was given orally at 5 or 20 mg/kg. Functional markers of liver function and
mitochondrial dysfunction were determined as well as hepatic assessment of apoptotic, oxidative, and inflammatory factors.
Capsaicin at the higher dose appropriately decreased serum level of
alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) in addition to reducing hepatic level of
malondialdehyde (MDA),
reactive oxygen species (ROS),
nitrite,
NF-kB, TLR4, IL-1β, TNF-α,
caspase 3, DNA fragmentation and boosting
sirtuin 1, Nrf2,
superoxide dismutase (SOD) activity, and
heme oxygenase (HO-1). These beneficial effects of
capsaicin were associated with reversal and/or improvement of gene expression for pro-apoptotic Bax, anti-apoptotic Bcl2, mitochondrial and metabolic regulators PGC-1α,
sirtuin 1, and AMPK, and
inflammation-associated factors. Additionally,
capsaicin exerted a hepatoprotective effect, as revealed by its reduction of liver histopathological changes. These findings evidently indicate hepatoprotective property of
capsaicin under septic conditions that can be attributed to its down-regulation of oxidative and inflammatory processes besides its potential to attenuate
mitochondrial dysfunction and apoptosis.