Abstract
Esculetin (ESC) is a coumarin that is present in several plants such as Fraxinus rhynchophylla and Artemisia capillaris. Our previous study found that FR ethanol extract (FREtOH) significantly ameliorated rats’ liver function. This study was intended to investigate the protective mechanism of ESC in hepatic apoptosis in rats induced by carbon tetrachloride. Rat hepatic apoptosis was induced by oral administration of CCl4. All rats were administered orally with CCl4 (20%, 0.5 mL/rat) twice a week for 8 weeks. Rats in the ESC groups were treated daily with ESC, and silymarin group were treated daily with silymarin. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) as well as the activities of the anti-oxidative enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase in the liver were measured. In addition, expression of liver apoptosis proteins and anti-apoptotic proteins were detected. ESC (100, 500 mg/kg) significantly reduced the elevated activities of serum ALT and AST caused by CCl4 and significantly increased the activities of catalase, GPx and SOD. Furthermore, ESC (100, 500 mg/kg) significantly decreased the levels of the proapoptotic proteins (t-Bid, Bak and Bad) and significantly increased the levels of the anti-apoptotic proteins (Bcl-2 and Bcl-xL). ESC inhibited the release of cytochrome c from mitochondria. In addition, the levels of activated caspase-9 and activated caspase-3 were significantly decreased in rats treated with ESC than those in rats treated with CCl4 alone. ESC significantly reduced CCl4-induced hepatic apoptosis in rats.
Highlights
Many chronic viral hepatitis patients have been treated with interferon, the results of the therapy have not always been satisfactory
The serum activities of ALT and AST were significantly elevated in the CCl4-treated group (p < 0.001) where ESC (100 and 500 mg/kg BW) significantly decreased the activities of serum
It is shown that chronic administration of CCl4 led to a marked increase in ALT and AST levels
Summary
Many chronic viral hepatitis patients have been treated with interferon, the results of the therapy have not always been satisfactory. ESC has been reported to inhibit oxidative damage induced by tert-butyl hydroperoxide in rat liver [9]. It has been isolated from various plants such as Artemisia capillaries, Citru slimonia and Euphorbia lathyris. ESC was demonstrated to inhibit CCl4-induced acute liver injury in rats. CCl4 is metabolized by cytochrome P450 2E1 to the trichloromethyl radical (CCl3−), which is assumed to initiate free radical-mediated lipid peroxidation leading to the accumulation of lipid-derived oxidation products that cause liver injury [10]. We examined the effect of ESC on CCl4-induced liver apoptosis in rats. Silymarin was used as a positive control drug
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