Carvacrol hinders the progression of hepatic fibrosis via targeting autotaxin and thioredoxin in thioacetamide-induced liver fibrosis in rat

Abstract

Fibrosis is a common outcome of nearly all chronic diseases of liver that results in changes of its functions which requires medical attention. The current research aims to investigate the potential anti-fibrotic efficacy of Carvacrol against thioacetamide (TAA)-induced liver fibrosis in male rats using Ursodeoxycholic acid (UDCA) as a reference anti-fibrotic product. Carvacrol (25 and 50 mg/kg) markedly declined TAA-increased serum liver enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) as well as total bilirubin (TB) and direct bilirubin (DB) levels as well as increased levels of total protein (TP) and albumin. Carvacrol significantly reduced glutathione depletion (GSH), Nitric oxide (NOX) and malondialdehyde (MDA) accumulation in liver tissue. Additionally, its anti-oxidant effect brightened up via affecting markers of stress found in the cell as nuclear factor erythroid 2-related factor 2 (Nrf-2) where it still had high content and decreased Thioredoxin (Trx) level. The anti-inflammatory effect of Carvacrol was confirmed by decreasing nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1β) and inducible nitric oxide synthase (iNOS) contents. Carvacrol showed anti-fibrotic effect clarified by turning down fibrosis-related markers; TGF-β1, matrix metalloproteinase-3 and 9 (MMP-3 and 9) and Autotaxin (ATX) contents. Furthermore, it decreased alpha smooth muscle actin (α-SMA) and caspase-3 immune-expression. The overall outcome of aforementioned markers results showed that Carvacrol suppresses the progression of liver fibrosis via its anti-oxidant, anti-inflammatory, anti-apoptotic effect and its ability in lowering Thioredoxin and Autotaxin; hence it can be categorized as a hepatoprotective natural substance.

Hepatoprotective activity of Lactéol® forte and quercetin dihydrate against thioacetamide‐induced hepatic cirrhosis in male albino rats

“…While serum levels of GGT were significantly increased as compared to the control group. These results were in agreement with Salama et al, 31 El-Gendy et al 37 and Ayoub et al 33 The combined administration of TAA with LF and QD showed a non-significant decrease in serum hepatic enzymes indicating that both may have a protective effect against TAA hepatotoxicity. The downregulating effect of LF and QD against serum-level enzymes was reported by Bahr et al 38 and Afifi et al, 39 respectively.…”

“…48 control rats. The same result was obtained by Đurašević et al 32 and El-Gendy et al 37 Furthermore, Abdel-Rahman et al 35 showed that the intraperitoneal injection of TAA (100 mg/kg) for 2 weeks resulted in a substantial increment in hepatic fibrosis markers as TGF-β1, collagen I, connective tissue growth factor (CTGF), focal adhesion kinase (FAK) and α-SMA. LF showed antifibrotic activity as demonstrated by the down-regulation of α-SMA-stained myofibroblast and collagen expression by Masson's trichrome.…”

Carvacrol preserves antioxidant status and attenuates kidney fibrosis via modulation of TGF-β1/Smad signaling and inflammation

“…42 Recent studies have proven the anti-inflammatory activity of CVL by modulating TNF-α, IL-1β, and NF-κB expression in rat models of diclofenac-induced kidney injury and thioacetamide-induced hepatic fibrosis. 43,44 In the current study, UUO-induction dramatically increased the renal recruitment of inflammatory cells and the pro-inflammatory cytokines TNF-α and IL-1β in the obstructed kidneys. However, we observed a marked decrease in inflammatory cell infiltration and low levels of TNF-α and IL-1β in the obstructed kidneys after CVL administration.…”

Oliveria decumbens Extract Exhibits Hepatoprotective Effects Against Bile Duct Ligation-Induced Liver Injury in Rats by Reducing Oxidative Stress

“…Carvacrol reduced glutathione depletion (GSH), NO, and MDA accumulation in liver tissue. The anti-inflammatory effect of carvacrol was confirmed by decreasing nuclear factor kappa B (NF-κB), IL-1β, and inducible nitric oxide synthase (iNOS) contents (57). Oral administration of carvacrol had a significant protective and antioxidant effect against D-GalN-induced damages by reducing AST, ALT, ALP, and GGT and increasing SOD, CAT, and glutathione peroxidase in the plasma and liver (58).…”