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.

Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators

“…In the liver, different SCFAs exert different effects, and regarding fibrosis, sometimes contrasting results have been found. For example, high doses of propionate are known to be hepatotoxic and are used to induce liver fibrosis in animal models [ 110 ]. In some studies, butyrate and acetate have shown anti-fibrotic properties through the deactivation of TGF-β signaling and of some non-canonical TGF-β pathways [ 111 , 112 ].…”

Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

“…Clinical data have shown that CoQ10 supplements can alleviate the oxidation level of type I, II, and III complexes in the respiratory chain, regulating OXPHOS and inhibiting mitochondrial dysfunction induced by MAFLD [155]. Alhusaini, A.M. et al found that liposome-encapsulated coenzyme Q could significantly reduce liver damage and fibrosis caused by propionic acid by inhibiting cytochrome C and mitochondrial fragmentation and simultaneously increasing the expression of Bcl-2 [156]. Tiefenbach, J. et al proposed that coenzyme Q and its analog Idebenone can act as PPARα/γ agonists and downregulate triglyceride and cholesterol levels, finally reducing the development of steatosis and MAFLD [157].…”