Acetyl-L-Carnitine and Liposomal Co-Enzyme Q10 Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid

Abstract

Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q₁₀ (L-CoQ₁₀) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ₁₀ were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ₁₀ with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ₁₀ modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ₁₀ showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.

Keywords: acetyl-L-carnitine; cytokeratin-18; liposomal-coenzyme Q10; propionic acid; transforming growth factor-β1.

Figure 1

Treatment with A-CAR and L-CoQ₁₀ either alone or in combination ameliorated serum AST, ALT, and LDH levels. Data are expressed as mean ± SEM (n = 6). *** p < 0.001.

Figure 2

Treatment with A-CAR and L-CoQ₁₀ either alone or in combination decreased hepatic MDA levels and increased SOD activity and GSH levels. Data are expressed as mean ± SEM (n = 6). * p < 0.05, ** p < 0.01, *** p < 0.001.

Figure 3

Treatment with A-CAR and L-CoQ₁₀ either alone or in combination decreased hepatic inflammatory biomarkers (IL-6 and TNF-α) and apoptotic biomarker (caspase-3). Data are expressed as mean ± SEM (n = 6). * p < 0.05, *** p < 0.001.

Figure 4

A-CAR and L-CoQ₁₀ suppressed hepatic expression levels of TGF-β and SMAD3 proteins in PRA-intoxicated rats. Representative blots show the changes in the expression of TGF-β and SMAD3 proteins in control and all treated groups. Data are expressed as mean ± SEM (n = 6). ** p < 0.01, *** p < 0.001.

Figure 5

A-CAR and L-CoQ₁₀ downregulated the hepatic expression of HMGB1 and CK18 mRNA in PRA-intoxicated rats. Representative RT-PCR gel electrophoresis shows variations in the expression levels of HMGB1 and CK18 mRNA in control and all treated groups. Data are expressed as mean ± SEM (n = 6). * p < 0.05, *** p < 0.001.

Figure 6

Histology of liver tissue stained with H&E, x400. (A) Liver tissue of control group with normal histological architecture and hepatocytes arranged in thin plates (black arrow). (B) Liver tissue of PRA-intoxicated group shows hepatocytes with intracytoplasmic vacuoles (red arrow), congested and dilated sinusoids (yellow arrow), and necrotic areas (blue arrow). (C) Liver tissue of A-CAR-treated group shows hepatic tissue with relatively normal structure, hepatocytes arranged in thin plates (black arrow), congested sinusoids (red arrow), and hepatocytes with binucleated nuclei (green arrow). (D) Liver section of L-CoQ₁₀-treated group shows intact lobular hepatic architecture, hepatocytes arranged in thin plates with mild hydropic degeneration (black arrow), congested sinusoids (red arrow), and focal area of necrosis (blue arrow). (E) A representative liver section of the group treated with the combination of L-CoQ₁₀ and A-CAR shows hepatic tissue with an almost normal structure and architecture, hepatocytes arranged in thin plates (black arrow), and a congested central vein (red arrow).