Coumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl(4)) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague-Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl(4), when compared to control values. Similarly, administration of CCl(4) increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress.
Among the antimicrobial mechanisms associated with macrophages, NO produced by iNOS plays a major role in intracellular killing, but the relationship between NO and phagocytic activity after injection of inflammatory agents into the peritoneal cavity is not clear. The aim of the present study was to investigate the effect of nitric oxide (NO) on macrophage function after treatment with intraperitoneal lipopolysaccharide (LPS) and the role of exogenous L-arginine administration in this event. Six experimental groups and one control group, each consisting of seven Wistar rats were used: Group I: Control; Group II: LPS; Group III: LPS+L-arginine; Group IV: LPS+L-arginine+Aminoguanidine; Group V: LPS+Aminoguanidine; Group VI: L-arginine; Group VII: Aminoguanidine. Macrophage phagocytic activity and total plasma nitrite levels were increased in the LPS group. In the LPS+L-arginine group, both the phagocytic activity and total plasma nitrite levels showed large increases. Administration of aminoguanidine (AG), a specific iNOS inhibitor, abolished macrophage phagocytic activity and total plasma nitrite levels in the LPS and LPS+L-arginine groups. As a result, we showed that NO produced by macrophages has a role not only in intracellular killing, but also in phagocytic activity.
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