Abstract
BackgroundCholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. The present study aims to evaluate the protective impact of an ascarid nematode Toxocara vitulorum extract (TvE) against alpha-naphthylisothiocyanate (ANIT)-induced cholangitis male wistar rat model compared to ursodeoxycholic acid (UDCA) as a standard drug.ResultsPretreatment with TvE and/or UDCA induced a marked reduction in the levels of liver function tests and malondialdehyde, while antioxidant markers were increased compared to cholestatic rats. Pretreatment with either TvE or combination before cholangitis induction attenuated the predominant Th1-related cytokines (IFN-γ and TNF-α) to Th2 (IL-13 and IL-10). TvE administration promoted higher expression levels of Bcl-2 protein and lower levels of caspase-3 compared to cholestatic rats.ConclusionsTreatment with TvE has improved the liver functions and elevated the levels of oxidative stress markers. The upregulation of Th2-related cytokines and suppression of apoptosis through caspase-3 might be considered as a potential mechanism of TvE. Thereby, this natural extract revealed an opportunity for use in treatment of cholangitis disease.
Highlights
Cholestasis is the major cause of bile acid accumulation leading to liver damage
The treatments with Toxocara vitulorum extract (TvE) and/or ursodeoxycholic acid (UDCA) caused a significant (P < 0.05) decrease in activities of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and GGT compared with ANIT group
The current study showed that TvE increased the levels of Bcl-2 protein and decreased the levels of caspase-3 protein, decreasing apoptosis, suggesting that suppression of apoptosis may be one potential mechanism of TvE against ANIT-induced liver cholangitis in rats
Summary
Cholestasis is the major cause of bile acid accumulation leading to liver damage. Chronic infection of worms can modulate the immune response towards T helper (Th)2-related cytokines. Liver cholestasis is a devastating liver condition defined as an impairment of bile flow that leads to toxic bile acid accumulation in hepatocytes (Li et al, 2019). It results in hepatocellular damage followed by inflammation, fibrosis, and liver cirrhosis (Jin et al, 2013). Research evidences demonstrate that an impairment of normal bile flow and excessive accumulation of potentially toxic bile acids are considered the most important conditions that induced autoimmune cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) (Terziroli et al, 2017). During PBC, patients develop a well-orchestrated immune reaction, both innate and adaptive, against mitochondrial antigens that targets intrahepatic biliary cells (Lleo, Marzorati, Anaya, & Gershwin, 2017)
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