Abstract
Purpose: To investigate the potential protective effect of oral repeated doses of thearubigins against acetaminophen-induced hepatotoxicity in mice.Methods: Mice were randomly divided into six groups (n=8) and administered the following: Control group (saline), acetaminophen group (saline), N-acetylcysteine group (500 mg/kg/day), and thearubigins groups (60, 70, 100 mg/kg/day). The drugs were given orally by gavage for seven days. On day 7, 1 h after the last dose of treatment, the mice (except control group) were given a single dose of acetaminophen (n-acetyl-p-aminophenol, APAP) orally by gavage (350 mg/kg) and then sacrificed 4 h post-APAP intake. Blood was collected for biochemical measurements and their liver were subjected to biochemical and histopathological assessment.Results: The acetaminophen group showed significant increases (p < 0.001) in serum alanine aminotransferase level, hepatic cytochrome P2E1 level, and serum and hepatic malondialdehyde levels. Moreover it showed significant decrease (p < 0.001) in serum and hepatic glutathione levels. Morphologically, the liver sections showed cellular necrosis, vacuolization, and degeneration around the centrilobular veins. Pretreatment with N-acetylcysteine reversed all acetaminophen-induced changes (p < 0.001 for all biomarkers except for hepatic MDA (p = 0.014) while pretreatment with thearubigins failed to reverse any of them.Conclusion: Oral repeated doses of thearubigins failed to protect against acetaminophen-induced hepatotoxicity in mice and didn't affect hepatic cytochrome P2E1 level.Keywords: Acetaminophen, Hepatotoxicity, Thearubigins, N-acetylcysteine, Cellular necrosis, Vacuolization, Hepatic cytochrome P2E1
Highlights
Acetaminophen (APAP) is safe when used in regular doses where nearly 95 % of it is metabolized in the liver by glucuronidation and sulfation to non-toxic metabolites
5 % is oxidized by CYP450 isozymes to n-acetyl-p-benzoquinone imine (NAPQI) which is reduced by glutathione (GSH) and excreted as mercapturic acid [1]
In our recently-published study [5], we found that intraperitoneal single dose thearubigins (TRs); the main phenolic pigment of black tea extract; dose-dependently protected against APAPinduced hepatotoxicity in mice
Summary
Acetaminophen (APAP) is safe when used in regular doses where nearly 95 % of it is metabolized in the liver by glucuronidation and sulfation to non-toxic metabolites. Acetaminophen causes acute liver failure due to saturation of the sulfation pathway and shifting of more APAP to the CYP450 pathway forming excessive NAPQI. This excessively-produced NAPQI severely depletes cellular GSH and covalently binds to cellular proteins with increased formation of free radicals causing mitochondrial damage, cellular necrosis, and organ failure. The present study was designed to investigate the potential hepatoprotective effect of oral pretreatment with TRs given to mice for seven days prior to oral administration of APAP on the seventh day. SPSS version 18.0 software was used in the statistical analysis and p < 0.05 was considered statistically significant
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
