title: The relative efficacy of aminoguanidine and pentoxifylline in modulating endotoxin-induced cardiac stress.
abstract: This study investigates the effect of aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and pentoxifylline (PTX), a tumour necrosis factor-alpha (TNF-α) inhibitor, on lipopolysaccharide (LPS)-induced cardiac stress. Rats were divided into four groups: group I served as a control, group II (LPS) received a single intraperitoneal injection of LPS (10 mg·kg(-1) ), group III (LPS+AG) and group IV (LPS+PTX) were injected with either AG (100 mg·kg(-1) ) or PTX (150 mg·kg(-1) ) intraperitoneally 10 days prior to LPS administration. Normalization of cardiac levels of nitrite/nitrate (NO(X) ), malondialdehyde (MDA), glutathione (GSH), heme oxygenase-1 (HO-1), glutathione peroxidase (GPx) and Na(+) , K(+) -ATPase activities was evident in the AG group. Both AG and PTX decreased the elevated serum TNF-α levels, the activities of lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac myeloperoxidase (MPO). The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and phosphocreatine (PCr) were enhanced following AG and PTX pretreatments. Calcium (Ca(2+) ) levels were altered, and the histopathological observations supported the described results. Conclusively, the study highlights the cardioprotective potential of AG and PTX with superior results from AG. These findings reveal the relative contribution of nitric oxide and TNF-α to oxidative stress and energy failure during endotoxemia.
authors: Biochemistry Department, Cairo University, Egypt.
authors: Tarek K
authors: TK
authors: Motawi
authors: Hebatallah A
authors: HA
authors: Darwish
authors: Azza M
authors: AM
authors: Abd El Tawab
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity*; D006146:Guanidines / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010431:Pentoxifylline / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004731:Endotoxins; D006146:Guanidines; D008070:Lipopolysaccharides; C004479:pimagedine; D010431:Pentoxifylline