title: Effects of caffeic acid phenethyl ester on endotoxin-induced cardiac stress in rats: a possible mechanism of protection.
abstract: Endotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including myocardial dysfunction. The present study aimed to investigate the mechanism of caffeic acid phenethyl ester (CAPE) protection against LPS-induced cardiac stress. Rats were allocated into three groups; group 1 served as a normal control group, group 2 (LPS) received a single intraperitoneal injection of LPS (10 mg/kg), group 3 (LPS + CAPE) was injected intraperitoneally with CAPE (10 mg/kg/day; solubilized in saline containing 20% tween 20) throughout a period of 10 days prior to LPS injection. Rats were maintained 4 h before sacrifice. Caffeic acid phenethyl ester pretreatment normalized LPS-enhanced activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH) as well as glutathione peroxidase (GPx), and myeloperoxidase (MPO) in cardiac tissue. A significant reduction of the elevated levels of serum tumor necrosis factor-alpha (TNF-α) as well as serum and cardiac nitrite/nitrate (NOx) ) was achieved after CAPE pretreatment. CAPE also restored malondialdelyde (MDA), reduced glutathione (GSH), and cytosolic calcium (Ca2+ ) levels in the heart. A marked induction of cardiac heme oxygenase-1 (HO-1) protein level was detected in CAPE-pretreated group. Whereas, LPS-induced reduction of adenosine triphosphate (ATP) and phosphocreatine (PCr) levels was insignificantly changed. Conclusively, the early treatment with CAPE maintained antioxidant defences, reduced oxidative injury, cytokine damage, and inflammation but did not markedly improve energy status in cardiac tissue. The beneficial effect of CAPE might be mediated, at least in part, by the superinduction of HO-1.
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo1 1562, Egypt.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Motawi
authors.forename: Hebatallah A
authors.initials: HA
authors.lastname: Darwish
authors.forename: Azza M
authors.initials: AM
authors.lastname: Abd El Tawab
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010725:Phosphocreatine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C055494:caffeic acid phenethyl ester; D005978:Glutathione; D010626:Phenylethyl Alcohol; D002118:Calcium