Abstract
Drug‐induced liver injury (DILI) is one of the common adverse effects of drug therapy, which is closely associated with oxidative stress, apoptosis, and inflammation response. Medium‐chain fatty acids (MCFA) were reported to relieve inflammation and attenuate oxidative stress. However, little has been known about the hepatoprotective effects of MCFA in DILI. In the present study, acetaminophen (AP) and rifampicin (RFP) were used to establish DILI models in LO2 cells, and the cytoprotective effects of MCFA on hepatocellular injury were investigated. Results showed that the optimal condition for the DILI model was treatment with 10 mM AP or 600 µM RFP for 24 hr. LCFA treatment markedly reduced the cell viability and increased the activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Meanwhile, LCFA treatment aggravated cell apoptosis, mitochondrial dysfunction, and oxidative stress. The mRNA and protein expression levels of inflammatory cytokines (IL‐1β and TNF‐α) were significantly elevated by LCFA. In contrast, MCFA treatment did not significantly affect cell viability, apoptosis, oxidative, stress and inflammation, and it did not produce the detrimental effects on DILI models. Therefore, we proposed that MCFA may be more safe and suitable than LCFA as nutrition support or the selection of daily dietary oil and fat for the patients with DILI.
Highlights
The liver is a vital organ of mammals and primarily responsible for maintaining nutrient homeostasis by regulating protein, carbohydrate, and fat metabolism, and exerting detoxification by decomposing and transforming various drugs and toxins, and excreting certain metabolites in the body
We first determined the conditions of AP and RFP to establish a Drug-induced liver injury (DILI) model in LO2 cells and investigated the effects of fatty acid (FA) on the hepatocellular injury
Compared with the long-chain fatty acids (LCFA) group, the fluorescence intensity in Medium-chain fatty acids (MCFA) groups increased from 66.9% to 72.9%, 72.0%, and 72.7% in AP model and from 65.4% to 73.4%, 72.3%, and 71.4% in RFP model, respectively. These results suggested that LCFA may decreased membrane potential (MMP), and MCFA did not affect MMP compared with the NR group in the AP or RFP model
Summary
The liver is a vital organ of mammals and primarily responsible for maintaining nutrient homeostasis by regulating protein, carbohydrate, and fat metabolism, and exerting detoxification by decomposing and transforming various drugs and toxins, and excreting certain metabolites in the body. We first determined the conditions of AP and RFP to establish a DILI model in LO2 cells and investigated the effects of fatty acid (FA) on the hepatocellular injury. Another study found that MCFA attenuated lipopolysaccharide-induced liver injury through down-regulating necroptotic and inflammatory signaling pathways (Zhang et al, 2018). These studies were hardly focusing on the relationship between FA and DILI, and many patients with DILI consumed LCFA (especially oleic acid) in daily oil and fat diets due to lack of scientific references.
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