Esculetin Ameliorates Carbon Tetrachloride-Mediated Hepatic Apoptosis in Rats

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.

Protective properties of sesamin against fluoride-induced oxidative stress and apoptosis in kidney of carp (Cyprinus carpio) via JNK signaling pathway

“…Previous studies indicated that the JNK-c-Jun/Ap1 pathway could increase the expression of pro-apoptotic genes, such as TNF-a, Fas-L, and Bak (Fan and Chambers, 2011;Dhanasekaran et al, 2008). Many studies showed that fluoride could increase renal apoptosis by mitochondrial extrinsic apoptotic pathways (Tien et al, 2011;Zhang et al, 2013). In this study, the expressions of p-JNK1/2, p-c-Jun, TNF-a, and Bak increased in the kidney of fluoride-exposed carp, which implied that the activation of JNK signaling pathway possibly played a important role in the renal damage of carp exposed to fluoride.…”

“…The activation of JNK has been implicated in the fish apoptosis induced by various chemical and biological agents (Datta et al, 2009;Banerjee et al, 2011). During the very important mitochondrial event launching apoptosis, cytochrome c could be released from the inner membrane space of mitochondria to the cytosol (Dhanasekaran et al, 2008;Sinha et al, 2013) and binds to apoptosis-activating factor, which stimulates caspase activity to modulate apoptosis (Dhanasekaran et al, 2008;Tien et al, 2011). JNKs also play an important role in regulating the functions of proand anti-apoptotic proteins in mitochondria.…”

“…JNKs also play an important role in regulating the functions of proand anti-apoptotic proteins in mitochondria. JNK combined with ROS can promote apoptosis by stimulating the activities of pro-apoptotic proteins (such as Bax, Bak, Bok, Bid, Bim, Bik, Bad, Bmf, Hrk, Noxa, Puma, Blk) and inhibiting the activities of anti-apoptotic proteins (such as Bcl-2, Bcl-XL, Bcl-w, A1, Mcl-1) (Tien et al, 2011;Sinha et al, 2013). Moreover, overproduction of ROS induced by fluoride can promote apoptotic process which can influence the permeability and inhibit the respiratory chain (Valko et al, 2006;Zhang et al, 2012).…”

“…The caspase pathway is well recognized as downstream target for JNK signaling in apoptosis (Dhanasekaran et al, 2008;Sinha et al, 2013). Activation of caspase-3, as the convergence of intrinsic and extrinsic pathways, is of very importance in apoptosis and is capable of cleaving or degrading crucial proteins in apoptosis, such as nuclear lamins, fodrin, and the nuclear enzyme poly polymerase (PARP), causing the concomitant degradation of nuclear DNA (Tien et al, 2011;Zhang et al, 2013). Increased expression of caspase-3 has been involved in apoptosis in a variety of organism (Abu-Qare and Abou-Donia, 2001).…”

Sub-Chronic Esculetin (6,7-Dihydroxy-Coumarin)-Induced Alteration in Some Haematological and Serum Parameters in Normal Male Wistar Rats

“…Esculetin (6,7-dihydroxycoumarin) is a coumarin (group of non-nutrient phenolic phytochemicals) derivative that is present in several plants, including Citrus limonia, Aesculus hippocastanum, Euphobia lathyris, Fraxinus rhynchophylla and Artemisia capillaris (Masamoto et al, 2003;Tien et al, 2011). Esculetin, like other coumarins, possesses diverse biological and pharmaceutical properties (Lacy and O'Kennedy, 2004) and is useful in drug synthesis (Kostova, 2005).…”