guanosine-triphosphate and Edema

Ischemia-reperfusion injury, a clinical problem during cardiac surgery, involves worsened adenosine trisphosphate (ATP) generation and damage to the heart. We studied carbon monoxide (CO) pretreatment, proven valuable in rodents but not previously tested in large animals, for its effects on pig hearts subjected to cardiopulmonary bypass with cardioplegic arrest. Hearts of CO-treated pigs showed significantly higher ATP and phosphocreatine levels, less interstitial edema, and apoptosis of cardiomyocytes and required fewer defibrillations after bypass. We conclude that treatment with CO improves the energy status, prevents edema formation and apoptosis, and facilitates recovery in a clinically relevant model of cardiopulmonary bypass surgery.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Apoptosis; Carbon Monoxide; Cardiopulmonary Bypass; Cardiotonic Agents; Edema; Electric Countershock; Energy Metabolism; Female; Guanosine Triphosphate; Heart; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocytes, Cardiac; NAD; NADP; Oxidation-Reduction; Sus scrofa

Studies from our laboratory have shown that epigallocatechin-3-gallate, the major polyphenol present in green tea, inhibits ultraviolet (UV)B-exposure-mediated phosphorylation of mitogen-activated protein kinases (MAPKs) (Toxicol. Appl. Pharmacol. 176: 110-117, 2001) and activation of nuclear factor kappa B (NF-kappaB) (Oncogene 22: 1035-1044, 2003) pathways in normal human epidermal keratinocytes. This study was designed to investigate the relevance of these findings to the in vivo situations in SKH-1 hairless mouse model, which is regarded to have relevance to human situations. SKH-1 hairless mice were topically treated with GTP (5 mg/0.2 ml acetone/mouse) and were exposed to UVB 30 min later (180 mJ/cm2). These treatments were repeated every alternate day for 2 weeks, for a total of seven treatments. The animals were killed 24 h after the last UVB exposure. Topical application of GTP resulted in significant decrease in UVB-induced bifold-skin thickness, skin edema and infiltration of leukocytes. Employing Western blot analysis and immunohistochemical studies, we found that GTP resulted in inhibition of UVB-induced: (i) phosphorylation of extracellular-signal-regulated kinases (ERK1/2), (ii) c-Jun N-terminal kinases, and (iii) p38 protein expression. Since NF-kappaB plays a major role in inflammation and cell proliferation, we assessed the effect of GTP on UVB-mediated modulations in the NF-kappaB pathway. Our data demonstrated that GTP inhibited UVB-induced: (i) activation of NF-kappaB, (ii) activation of IKKalpha, and (iii) phosphorylation and degradation of IkappaBalpha. Our data suggest that GTP protects against the adverse effects of UV radiation via modulations in MAPK and NF-kappaB signaling pathways, and provides molecular basis for the photochemopreventive effect of GTP in an in vivo animal model system.

Topics: Animals; Blotting, Western; Cell Division; Cell Nucleus; Edema; Female; Flavonoids; Guanosine Triphosphate; Hyperplasia; I-kappa B Kinase; I-kappa B Proteins; Immunohistochemistry; Leukocytes; MAP Kinase Signaling System; Mice; Mice, Hairless; Mice, Mutant Strains; Mitogen-Activated Protein Kinases; NF-kappa B; NF-KappaB Inhibitor alpha; Phenols; Phosphorylation; Polyphenols; Protein Serine-Threonine Kinases; Signal Transduction; Skin; Tea; Time Factors; Ultraviolet Rays

Jigrine, a polypharmaceutical herbal formulation containing 14 medicinal plants is used in the Unani system of medicine for the treatment of liver ailments. The antiinflammatory activity of Jigrine (0.5 ml and 1.0 ml/kg, po), was evaluated against acute inflammation caused by carrageenin (injecting 0.1 ml of 1% carrageenin in 0.9% NaCl solution into plantar surface of the hind paw of the rat) and the effect of Jigrine (1 ml/kg/day, po for 7 days) was also studied on the sub-acute inflammation induced by cotton pellet granuloma. The paw volume, biochemical parameters like tissue AST, ALT, gamma-GTP and lipid peroxides and dry wt. of granuloma were measured to assess the anti-inflammatory activity. It showed a significant anti-inflammatory activity as evidenced by lowering the elevated levels of paw volume and biochemical parameters. But it could not reduce the sub-acute inflammation caused by cotton pellet granuloma. The study suggests that Jigrine has significant effect only on acute phase of inflammation caused by carrageenin. Antioxidant and membrane stabilizing action of Jigrine might be responsible for its anti-inflammatory effect.

Topics: Alanine Transaminase; Analysis of Variance; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Carrageenan; Disease Models, Animal; Edema; Granuloma; Guanosine Triphosphate; Hindlimb; India; Lipid Peroxidation; Male; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar