6-ketoprostaglandin-f1-alpha and Chemical-and-Drug-Induced-Liver-Injury

This study was to evaluate the protective effects of Danshensu on liver injury induced by omethoate in Sprague Dawley rats. The acute omethoate poisoning model was established by administrating subcutaneously with omethoate at a single dose of 60 mg/kg. Danshensu treatment markedly inhibited the increases of aspartate aminotransferase, alanine aminotransferase, cyclooxygenase-2, tumor necrosis factor-alpha, thromboxane B(2), and thromboxane B(2)/6-keto-PGF1alpha ratio induced by omethoate. The histopathological examination further confirmed that administration with Denshensu ameliorated liver injury. The results demonstrated that Danshensu possesses protective action on hepatic injury induced by omethoate and the pharmacological mechanism was related to the anti-inflammatory effect and circulation improvement of Danshensu, at least in part.

Topics: 6-Ketoprostaglandin F1 alpha; Alanine Transaminase; Animals; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Chemoprevention; Cyclooxygenase 2; Dimethoate; Disease Models, Animal; Drugs, Chinese Herbal; Injections, Subcutaneous; Lactates; Liver; Male; Rats; Rats, Sprague-Dawley; Thromboxane B2; Tumor Necrosis Factor-alpha

A beneficial effect of flavonoids in Cl(4)C-induced hepatoxicity in rats has been reported. In this communication we have evaluated the protective effect of astilbin, an active flavonoid isolated from a crude extract of Hymenaea martiana, as well as its action on liver arachidonate metabolism in Cl(4)C-treated rats. The following groups of rats were studied: Group I = controls; Group II = Astilbine-treated animals (40 mg/Kg); Group III = Cl(4)C-treated at 1 ml/kg; Group IV = Astilbine + ClC4 and Group V = Vitamine E (50 mg/Kg) + Cl(4)C-treated animals. Histological findings, superoxide dismutase activity, lipoperoxides and prostanoid profiling studies revealed that the hepatoprotective effect of astilbine was higher than that of vitamin E. Astilbine was capable to restore lipoperoxides and tissue prostanoids to basal values.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Dinoprostone; Female; Flavonoids; Flavonols; Free Radicals; Lipid Peroxidation; Liver; Liver Diseases; Malondialdehyde; Molecular Structure; Phospholipases A; Prostaglandins; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Thromboxane B2; Vitamin E

The changes of the levels of LTC4, PGI2 and TXA2 in the liver tissue in SD rats with GaIN/LPS-induced acute liver injury was studied with radioimmunoassay (RIA). As a result, 12 h after the administration of GaIN/LPS, serum AST (398 +/- 37 u), ALT (565 +/- 43 u) increased (P < 0.001) and the concentration of TXA2 (12,188 +/- 588 pg/g.w.wt) in liver tissue increased significantly (P < 0.001), while the content of LTC4 (9713 +/- 3557 ng/g.w.wt) and PGI2(1748 +/- 560 pg/g.w.wt) in liver tissue were not obviously changed (P > 0.05) and the inflammatory changes of the pathological findings were observed. The improvement of serum ALT (330 +/- 168 u) (P < 0.05) and AST (273 +/- 124 u) (P < 0.05) and histopathological damage was observed after the administration of diethylcarbamazine (DEC), a LTA4 synthesis inhibitor, the liver TXA2 (12,740 +/- 699) concentration significantly increased (P < 0.001), while the levels of LTC4 (8179 +/- 1653) and PGI2 (2320 +/- 630) were not obviously changed. Serum ALT (536 +/- 74 u) and AST (416 +/- 41 u) (P > 0.05) levels and histopathology did not change with administration of indomethacin, a cyclooxygenase inhibitor, but the liver LTC4 (12,166 +/- 1327) contents increased (P < 0.05) and TXA2 (1868 +/- 791) reduced significantly (P < 0.001). The present study suggests that arachidonic acid metabolism in rats with acute liver injury are significantly abnormal. Leukotrienes and thromboxane are important inflammatory mediators in the liver injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Chemical and Drug Induced Liver Injury; Endotoxins; Galactosamine; Liver; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Thromboxane B2

To investigate the effective ingredients of Salvia miltiorrhizae on anti-liver injury, the water soluble component of the above drug, magnesium lithosperamate B, was used to conduct the experimental treatment of acute liver injury by D-galactosamine (10 mg/kg body weight, orally). The results showed that the component could obviously attenuate the necrosis of liver tissues, lower the activities of serum alanine amino transferase (ALT) and aspartate amino transferase (AST), P < 0.05. Compared with those of the normal rats, the levels of the products of cyclo-oxygenase (6-keto-prostaglandin F1 alpha, prostaglandin D2 and total prostaglandins) in the metabolism of arachidonic acid in non-parenchymal cells of acute liver-injured rats were markedly decreased (P < 0.05). These data revealed that magnesium lithosperamate B might be one of the main components of Salvia miltiorrhizae in anti-liver injury, while increasing the levels of total prostaglandins in liver non-parenchymal cells was perhaps one of the mechanisms of anti-liver injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Chemical and Drug Induced Liver Injury; Drugs, Chinese Herbal; Galactosamine; Liver; Male; Prostaglandin D2; Rats; Rats, Wistar

Multiple extrapulmonary organ system failures increase mortality, permeability edema, and alveolar inflammation during gram-negative sepsis because of abnormal regulation of host inflammatory responses. We tested the hypothesis that acute hepatocytic injury induced by the selective hepatotoxin, D-galactosamine (GalN), augments mortality and amplifies pulmonary microvascular permeability to albumin and neutrophilic influx after administering Escherichia coli lipopolysaccharide (LPS) 24 h later by impairing the metabolism of endogenously synthesized products of arachidonic acid. We determined the lung extravascular leak of 125I-human serum albumin measured at multiple time points after LPS and enumerated polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF). Because the liver is important in prostaglandin (PG) and leukotriene (LT) metabolism, we measured plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) in addition to paired plasma BALF concentrations of LTB4 and BALF LTC4 60 min and 24 h after LPS. We further assessed the protective effects of a single 20-mg/kg injection given intraperitoneally (i.p.) of the LTA4 synthetase inhibitor, diethylcarbamazine (DEC). After 400 mg/kg GalN, LPS at 2.5 or 1.25 mg/kg i.p. increased mortality (p less than 0.001), albumin leak 60 and 90 min after LPS (p less than 0.05), plasma 6-keto-PGF1 alpha, TxB2, and LTB4 levels and BALF LTC4 within 60 min (p less than 0.05). LTB4 and LTC4 levels in BALF 24 h later were similarly increased (p less than 0.05) as were bronchoalveolar PMNs (p less than 0.001). DEC improved mortality and albumin leak (p less than 0.001), reduced lung influx of PMNs and peripheral leukocytosis (p less than 0.05), attenuated plasma LTB4 and BALF LTC4 levels 60 min after LPS (p less than 0.05), and decreased BALF LTB4 and LTC4 at 24 h (p less than 0.05), but was associated with higher plasma 6-keto-PGF1 alpha and TxB2 values at 60 min. Changes in eicosanoid levels and modulation of responses by DEC in this model suggest that impaired metabolism of endogenously synthesized leukotriences by the damaged liver underlies these phenomena. We conclude that this mechanism may enhance septic lung injury during acute liver dysfunction.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Capillary Permeability; Chemical and Drug Induced Liver Injury; Escherichia coli; Galactosamine; Leukotrienes; Lipopolysaccharides; Lung; Male; Rats; Rats, Inbred Strains; Sepsis; Thromboxane B2