Effects of açai on oxidative stress, ER stress, and inflammation-related parameters in mice with high fat diet-fed induced NAFLD - PubMed (original) (raw)

Mayara Medeiros de Freitas Carvalho et al. Sci Rep. 2019.

Abstract

Non-alcoholic fatty liver disease (NAFLD), the most predominant liver disease worldwide, is a progressive condition that encompasses a spectrum of disorders ranging from steatosis to steatohepatitis, and, ultimately, cirrhosis and hepatocellular carcinoma. Although the underlying mechanism is complex and multifactorial, several intracellular events leading to its progression have been identified, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, and altered endoplasmic reticulum (ER) homeostasis. Phenolic compounds, such as those present in açai (Euterpe oleracea Mart.), are considered promising therapeutic agents due to their possible beneficial effects on the prevention and treatment of NAFLD. We tested in vitro effects of aqueous açai extract (AAE) in HepG2 cells and its influence on oxidative stress, endoplasmic reticulum stress, and inflammation in a murine model of high fat diet-induced NAFLD. In vitro AAE exhibited high antioxidant capacity, high potential to inhibit reactive oxygen species production, and no cytotoxicity. In vivo, AAE administration (3 g/kg) for six weeks attenuated liver damage (alanine aminotransferase levels), inflammatory process (number of inflammatory cells and serum TNFα), and oxidative stress, through the reduction of lipid peroxidation and carbonylation of proteins determined by OxyBlot and modulation of the antioxidant enzymes: glutathione reductase, SOD and catalase. No change was observed in collagen content indicating an absence of fibrosis, stress-related genes in RE, and protein expression of caspase-3, a marker of apoptosis. With these results, we provide evidence that açai exhibits hepatoprotective effects and may prevent the progression of liver damage related to NAFLD by targeting pathways involved in its progression.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Figure 1

Effects of AAE on cell viability. HepG2 cells were incubated for 24, 48, and 72 h with indicated concentrations of sterile AAE using the MTT method. The assay was performed in octuplicate, using untreated cells as a control (CC), to which 100% cell viability was attributed. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001, ANOVA followed by the Bonferroni test.

Figure 2

Figure 2

AAE inhibits the formation of EROS induced by tert-butyl hydroperoxide (TBHP) in HepG2 cells and different concentrations of AAE. The assay was performed in octuplicate, using untreated cells (CC) and cells treated with TBHP (C+), as controls. Significantly different values are marked with different superscript letters.

Figure 3

Figure 3

AAE reduces steatosis and inflammation. (a) Representative pictures of liver tissue stained with Masson’s trichrome from various experimental groups. White arrows indicate the presence of inflammatory infiltrate and black arrows point to macrovesicular steatosis. C: Control, A: AAE, HF: High-fat, HFA: High-fat + AAE. Bar = 50 μm; 20× magnification. (b) Number of inflammatory cells. (c) Total collagen area. In (b,c), data are represented as the means ± standard deviation. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ANOVA followed by the Bonferroni test.

Figure 4

Figure 4

AAE improves oxidative stress. Levels of oxidative stress biomarkers MDA/TBARS (a) and oxidized protein (b) in mice. Values are expressed as the means ± SEM (n = 8 and 6, respectively). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ANOVA followed by the Bonferroni test.

Figure 5

Figure 5

Relative mRNA expression of genes in the liver involved in ER stress pathways and apoptosis in mice. Bip/Grp78 (chaperone protein); Atf4: activity transcription factor 4; Chop: C/EBP homologous protein; sXbp1: spliced X-box-binding protein-1. Values are expressed as the means ± SEM (n = 6); Significantly different values are marked with different superscript letters.

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