Kojic acid induces oxidative stress and anti-inflammatory effects in human hepatocellular carcinoma (HepG2) cells

Abstract

The cosmetic industry makes extensive use of kojic acid (KA); however, the toxicity of KA in humans is not well known. By monitoring oxidative stress, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) signalling in human hepatoma (HepG2) cells after a 24 h exposure, this study aimed to identify the toxicity of KA. KA toxicity [4.22, 8.02 and 12.67 mM] was assessed using mitochondrial output, antioxidant responses, macromolecule damage, MAPK signalling, inflammation, and cell death markers, using spectrophotometry, luminometry, Western blot and qPCR. Apoptosis was confirmed by reduced cell viability and increased caspases −9 (p < 0.0001), −8 (p = 0.0003), and −3/7 (p < 0.0001) activities at 4.22 mM and 8.02 mM. LDH leakage was present at 12.67 mM, providing significant evidence of necrosis. Malondialdehyde (MDA) levels significantly increased at 4.22 mM (p < 0.0001). There was an increase of phosphorylated nuclear factor erythroid-2 factor-2 (p-Nrf2) at 4.22 mM and 8.02 mM, whilst at 12.67 mM decreased p-Nrf2 (p < 0.0001) was observed. KA increased p38 expression (p = 0.0011). The findings point to significant suppression of the NFκB inflammatory pathway at 8.02 mM (p < 0.0001). This study showed that KA initiated MAPK signalling due to oxidative stress and suppressed inflammation. HepG2 cells showed minimal toxicity to KA.