Protective effects of coumarin and coumarin derivatives against carbon tetrachloride-induced acute hepatotoxicity in rats

Department of Physiology, Faculty of Medicine, Dicle University, Diyarbakır 21280, Turkey.
Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie (Impact Factor: 1.86). 03/2010; 63(4):325-30. DOI: 10.1016/j.etp.2010.02.006
Source: PubMed


The comparison of the antioxidant activity of some coumarins with their molecular structure is well determined. However, the protective function of coumarins with various chemical structures against liver toxicity has not yet been well established. Therefore, the aim of this study was to evaluate the possible cytoprotective properties of coumarin and some coumarin derivatives against CCl(4) (carbon tetrachloride)-induced hepatotoxicity. Coumarin (1,2-benzopyrone) and coumarin derivatives esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin) and 4-methylumbelliferone (7-hyroxy-4-methyl) were examined for their protective effect against CCl(4)-induced hepatotoxicity in Male Sprague-Dawley rats. A single toxic dose of CCl(4) (1.25 ml kg(-1), orally) produced liver damage in rats, seen histologically as centrilobular necrosis. Administration of CCl(4) increased serum enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). Pre-treatment of rats with esculetin (31.15 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced increase in serum enzymes, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Morphological findings were consistent with the plasma transaminase observations. Among the coumarin analogs, esculetin, which possesses orthodihydroxy coumarins, showed the strongest protective effect against CCl(4)-induced liver damage, followed by scoparone, 4-methylumbelliferone and coumarin, respectively. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of liver toxicity.

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Available from: Hakkı Murat Bilgin, Jul 24, 2014
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    • "Coumarins have been previously considered as benzoic acid derivatives but the classical approach by W. H. Perkin, Sr. classified them as oxygenated heterocycles [10e12]. Various pharmacological activities of coumarins basically depend on the type of coumarin nucleus which includes antibacterial [13] [14], cycloxygenase inhibiton [15], antimutagenic [16], scavanging of reactive oxygen species (ROS) [17] [18], antiinflammatory [19] [20], anticoagulant [21e23], lipoxygenase [24] [25], CNS stimulants [26], antithrombotic [27] [28], vasodilatory [29] [30], and anticancer activity [31] "
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    European Journal of Medicinal Chemistry 07/2015; 101:476-495. DOI:10.1016/j.ejmech.2015.07.010 · 3.45 Impact Factor
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    • "Hydroxyl derivatives of coumarins can also act as free radical scavengers, an action that is correlated with the number of hydroxyl groups in their structure (Lin et al. 2000; Huang et al. 2005). Thus, coumarins that possess hydroxyl groups are more potent free radical scavengers than their methoxy-substituted derivatives (Bilgin et al. 2011). The rise in ROS levels, the disruption of the antioxidant system during ethanol intoxication, and the increased levels of free iron ions together lead to elevated oxidative stress and enhanced interactions between free radicals and lipids, which Table 2 Lipid peroxidation products (4-HNE, 8-isoPGF 2α, and NPs) in the brain of rats chronically intoxicated with ethanol and rats drinking sweet grass beverage and chronically intoxicated with ethanol "
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    • "Different capital letters indicate statistical differences among columns (species) and different lower case letters indicate significant statistical differences among lines (p < 0.001). inhibiting anaphylaxis in rats (Choi and Yan, 2009), as a potent hepatoprotective (Bilgin et al., 2011) and inducing the release of dopamine (Yang et al., 2010). The leishmanicidal activity of several coumarins has been reported to inhibit parasite growth in vitro. "
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