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G Hotter

Publications and source records attributed to G Hotter.

At least 55 records · Page 3Linked to original sources
PubMed1995

Altered levels of urinary prostanoids in lead-exposed workers.

This paper describes the alteration of the urinary excretion of prostanoids in workers occupationally exposed to lead. For this purpose, the following groups were studied: Group 1 (n = 62): controls; Group 2 (n = 29): risk group; and Group 3 (n = 69): exposed group. Urine samples were collected for prostanoid analysis and lead blood levels were analyzed. Our results demonstrate that urinary excretion of prostanoids is already altered even at levels of lead in blood = 200 micrograms/l. Owing to their sensitivity, urinary prostanoids could be useful markers of early renal changes associated with lead exposure. However, underlying mechanisms should be elucidated and the health significance of such changes should be assessed before any conclusion is drawn.

Adult↗
PubMed1995

Prostanoids and cyclosporin-mediated nephrotoxicity in rats: a critical appraisal.

The involvement of arachidonic acid metabolism in cyclosporin (CsA) nephrotoxicity depending on CsA vehicle has been explored in this study. For this purpose creatinine clearance, urinary excretion and renal levels of eicosanoids were measured in the following rat experimental groups: group I, control; group II, CsA was administered in olive oil by gavage at 15 mg/kg/d for 7 d; group III, same as group II but 30 mg/kg/d; group IV, CsA was administered in fish oil by gavage at 15 mg/kg/d for 7 d; group V, same as group IV but 30 mg/kg/d; group VI, CsA was administered in olive oil at 15 mg/kg/d with prednisolone (1 mg/kg/d). The results indicate that (1) CsA nephrotoxicity and prostanoid alterations seem to be greatly improved when fish results indicate that (1) CsA nephrotoxicity and prostanoid alterations seem to be greatly improved when fish oil substitutes olive oil as a vehicle for CsA administration and (2) a correlation was found between eicosanoids measured and renal function, except in group II in which creatinine clearance remains unmodified but eicosanoids were altered, thus suggesting that other factors play a role in mediating nephrotoxicity due to cyclosporin.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The impact of arterialization on prostanoid generation after liver transplantation in the rat.

Arterial reconstruction is not applied in most studies of hepatic transplantation. Differences in some parameters related to the microcirculatory status, depending on whether the graft has been subjected to both arterial and venous or only venous reconstruction have been demonstrated. We have evaluated whether arterialization has an effect on the production of inflammatory event-related mediators such as eicosanoids and oxygen free radicals. For this purpose, we have measured tissue eicosanoid levels, lipid peroxidation, and superoxide dismutase activity in livers subjected to arterial and venous or only venous reconstruction. No changes were observed in lipid peroxidation or superoxide dismutase activity when single and double revascularization were compared. Prostacyclin and thromboxane metabolites showed increased levels after 24-hr preservation when only venous reconstruction was carried out. In contrast, these metabolites remained unaltered when double revascularization was performed. This result suggests that eicosanoid metabolism is altered only when venous reconstruction was employed, and this fact can help explain microcirculatory changes reported in this experimental model of liver transplantation.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Prostanoid generation in early stages of acute pancreatitis: a role for nitric oxide.

The role of nitric oxide in eicosanoid and oxygen-free radical production in the early stages of sodium taurocholate-induced acute necrotizing pancreatitis has been studied. Male Wistar rats were divided into three groups: group I: control group, a volume of 0.1 ml/100 g body wt saline solution was injected at low pressure in the pancreatic duct; group II: acute pancreatitis was induced by administration of 3.5% sodium taurocholate; and group III: intravenous administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) 5 min before induction of acute pancreatitis as stated for group II. At 5 and 60 min after induction of pancreatitis, blood and pancreas tissue samples were taken for assays. Increases in 6-keto PGF1 alpha, TXB2, PGE2, PGF2 alpha, and 12-HETE were observed in the pancreatic tissue. Lipoperoxidation was also enhanced and remained unaltered after nitric oxide inhibition. The fact that nitric oxide synthase inhibition could only reverse the increases in 6-keto PGF1 alpha and TXB2 levels indicates that in acute pancreatitis endothelial and platelet eicosanoid generation is mediated through an nitric oxide-dependent mechanism. In contrast, nitric oxide appears to be not related with oxygen free radical damage associated with acute pancreatitis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Prostanoids and oxygen free radicals in early stages of experimental acute pancreatitis.

The aim of this work is to establish a relationship between prostanoids and oxygen free radicals in the early stages of acute pancreatitis induced by sodium taurocholate and to study the possible cytoprotective effects of exogenous prostaglandin administration. Tissue prostanoid production (6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2) was studied after induction of an acute pancreatitis by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg). The effect of previous administrations of 16,16-dimethyl prostaglandin E2 (0.5 microgram/kg), indomethacin (20 mg/kg), or superoxide dismutase (13 mg/kg) was evaluated. Early pancreatitis induced significant increases of the three prostanoid levels as soon as 5 min after taurocholate administration. The administration of 16,16-dimethyl prostaglandin E2 was able to maintain the tissue prostanoid production at basal levels while superoxide dismutase treatment only partially prevented the increase of 6-keto-prostaglandin F1 alpha. On the other hand, indomethacin pretreatment, as expected, prevented the taurocholate-induced early prostanoid biosynthesis but increased the mortality, suggesting that endogenous prostanoids play a role in cellular defense mechanisms. The effect of superoxide dismutase suggests that oxygen free radicals are responsible, in part, for prostanoid enhanced biosynthesis in the earlier stages of necrohemorrhagic pancreatitis.

16,16-Dimethylprostaglandin E2↗
PubMed1994

Liver lipoxygenase arachidonic acid metabolites in streptozotocin-induced diabetes in rats.

We have studied the liver 15-hydroxyeicosatetraenoic acid (15-HETE) and leukotriene B4 (LTB4) levels in streptozotocin- (ST)-induced diabetes in rats using liquid chromatography and radioimmunological techniques. Diabetic rats showed significant alterations of liver lipoxygenase metabolites when compared to controls. These 15-HETE and LTB4 increases were concomitant with raised levels of plasma and tissue thromboxane B2 (TXB2) and also urinary 2,3-dinor-TXB2 in plasma and urine, respectively. These changes confirm an activation of 5- and 15-lipoxygenase in the liver 3 days after i.p. ST administration.

Animals↗
PubMed1994

Effect of a platelet-activating factor antagonist and desferrioxamine administration on eicosanoid production in rat pancreas transplantation.

Eicosanoid metabolism and its relationship with platelet-activating factor and oxygen free radical production in rat pancreas transplantation has been studied herein. Male Sprague-Dawley rats were classified in 4 experimental groups (n = 8 each) as follows: group 1, control; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 with desferrioxamine administration before revascularization of the organ in the recipient rat; and group 4, same as group 3 with administration of a platelet-activating factor antagonist (BN-52021). The results show post-transplantation increases in eicosanoid production in pancreatic tissue. The fact that desferrioxamine and BN-52021 administration could reverse increases in thromboxane B2, leukotriene B4, and 12-hydroxyeicosatetraenoic acid but only BN-52021 affected 6-keto-PGF1 alpha levels suggests the existence of a close relationship between platelet-activating factor and oxygen free radical in eicosanoid production in pancreas transplantation and it points to a differential role of metabolites produced by circulatory cells and endothelial cells.

Animals↗
PubMed1994

Nephron target sites in chronic exposure to lead.

With established urinary markers of kidney integrity the early renal effects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-exposed workers and 45 age-matched controls (median blood lead concentrations 2.03 and 0.34 mumol/l respectively) not only well-established but also new urinary markers of renal integrity preferentially or exclusively located along the different nephron segments were analysed. Markers related to the glomerulus were 6-keto-prostaglandin 1 alpha, thromboxane B2, mainly produced in the glomerulus, and the extracellular matrix protein fibronectin. Markers of the proximal tubule were the brush-border antigens BBA, BB50, and HF5 and the intestinal alkaline phosphatase. Prostaglandin E2 and F2 alpha, preferentially synthesized in the collecting duct and medullary interstitial cells, served as markers of these more distal nephron segments. In contrast to previous studies on the early phase of lead nephrotoxicity, not only tubular but also glomerular involvement could be shown in the study presented here by increases in the median values of 6-keto-prostaglandin 1 alpha and decreases in fibronectin. The proximal tubular markers intestinal alkaline phosphatase and BBA confirmed that this particular segment of the nephron is affected by lead. Effects on the collecting tubule or medullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that combinations of new and established markers could be valuable for a better definition and early detection of lead nephropathy.

Adult↗
PubMed1994

Arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation.

The implication of eicosanoid metabolism and its relationship with oxygen free radical production in the process of ischemia-reperfusion associated with rat pancreas transplantation has been explored in this study. For this purpose male Sprague-Dawley rats were classified as follows: group I, control animals not surgically manipulated; group II, pancreas transplantation, after 30 min preservation in UW solution; group III, pancreas transplantation after 12 h preservation under the same conditions; group IV, same as group III but with administration of SOD 5 min prior to organ revascularization. The results show post-transplantation increases in 6-keto-PGF1 alpha, TXB2, LTB4 and 12-HETE in pancreatic tissue independent of preservation time. The fact that SOD administration could reverse these increases even though an efficient xanthine oxidase irreversible inhibitor such as allopurinol was present in the preservation solution suggests that eicosanoid generation in the recipient rat would be mediated by an oxygen free radical dependent mechanism not exclusively dependent on endothelial xanthine oxidase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Liquid chromatography and radioimmunoassay method for the determination of prostaglandins E1 and E2 in rat embryo incubates.

This paper describes the application of a combined high-performance liquid chromatography and radioimmunological assay method for the measurement of prostaglandins E1(PGE1) and E2(PGE2). Samples were acidified to pH 3.15, extracted twice with ethyl acetate and further processed through C18 solid-phase extraction cartridges. After HPLC purification, PGE1 and PGE2 were measured by radioimmunological techniques. The limit of detection for PGE1 was 3.9 pg/ml and the intra-assay relative standard deviation was 7.8% for n = 5. The accuracy of the assay procedure was also verified. The method has been applied to the determination of PGE1 and PGE2 in embryo incubates from 10-day pregnant rats.

Alprostadil↗
PubMed1993

Changes of systemic prostacyclin and thromboxane A2 in sodium taurocholate- and cerulein-induced acute pancreatitis in rats.

Systemic prostacyclin and thromboxane A2 production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 micrograms/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2 were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A2 activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Altered leukotriene B4 levels by HL-60 cells after monocytic/macrophage differentiation.

The differentiation of HL-60 human promyelocytic leukaemia cells into specific monocytic or granulocytic lineage cells depending of the inductor agent is accompanied by selective regulation of several key enzymes involved in the synthesis of eicosanoids. In this communication we have investigated the changes in arachidonic acid metabolic profiles during phorbol 12-myristate 13-acetate (PMA)-induced monocytic differentiation of HL-60 cells. Our results show that HL-60 cells have spontaneous capacity to synthesize large amounts of LTB4, but PMA-differentiated cells lose the ability to release LTB4. Significant differences are found between HL-60 cells and PMA-treated cells in basal conditions and under ionophore stimulation. The addition of LTB4 at the time of PMA differentiation did not have effects on cell proliferation, but nordihydroguaiaretic acid (NDGA), a potent 5-lipoxygenase inhibitor, also inhibited HL-60 cell proliferation and did not have any effect on PMA-differentiated cell proliferation.

Arachidonic Acids↗
PubMed1993

Cyclooxygenase and lipoxygenase metabolism in sodium taurocholate induced acute hemorrhagic pancreatitis in rats.

Several studies have reported that prostanoids are involved in many of the physiopathological mechanisms underlying acute pancreatitis but their precise role in this disease remains to be established. The objective of this work is to evaluate the variation of local tissue production of prostanoids and lipoxygenase metabolites of arachidonic acid in acute pancreas inflammation induced by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg body weight) in rats. Pancreatic tissue levels of leukotriene B4 (LTB4), 15 hydroxyeicosatetraenoic acid (15-HETE), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were determined by HPLC-RIA techniques at 5 and 60 minutes after induction of acute pancreatitis (AP). Prostanoids increased significantly at 5 minutes and LTB4 and 15-HETE at 60 minutes. These data confirm that the prostanoid imbalance could be considered as an early specific response of the pancreas to the inflammatory events characteristic of induced AP while the altered levels of the lipoxygenase products (LTB4 and 15-HETE) would be more of a nonspecific organ response associated to the high cellular infiltration rate and necrosis observed in the late phases of acute pancreatitis.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour.

Several markers of renal changes have been measured in a cohort of 50 workers exposed to elemental mercury (Hg) and in 50 control workers. After application of selection criteria 44 exposed and 49 control workers were retained for the final statistical analysis. Exposed workers excreted on average 22 micrograms Hg/g creatinine and their mean duration of exposure was 11 years. Three types of renal markers were studied--namely, functional markers (creatinine and beta 2-microglobulin in serum, urinary proteins of low or high molecular weight); cytotoxicity markers (tubular antigens and enzymes in urine), and biochemical markers (eicosanoids, thromboxane, fibronectin, kallikrein, sialic acid, glycosaminoglycans in urine, red blood cell membrane negative charges). Several bloodborne indicators of polyclonal activation were also measured to test the hypothesis that an immune mechanism might be involved in the renal toxicity of elemental Hg. The main renal changes associated with exposure to Hg were indicative of tubular cytotoxicity (increased leakage of tubular antigens and enzymes in urine) and biochemical alterations (decreased urinary excretion of some eicosanoids and glycosaminoglycans and lowering of urinary pH). The concentrations of anti-DNA antibodies and total immunoglobulin E in serum were also positively associated with the concentration of Hg in urine and in blood respectively. The renal effects were mainly found in workers excreting more than 50 micrograms Hg/g creatinine, which corroborates our previous estimate of the biological threshold of Hg in urine. As these effects, however, were unrelated to the duration of exposure and not accompanied by functional changes (for example, microproteinuria), they may not necessarily represent clinically significant alterations of renal function.

Adult↗
PubMed1993

Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium.

Cadmium (Cd) was the third heavy metal investigated in the European collaborative research project on the development and validation of new markers of nephrotoxicity. Fifty workers exposed to Cd and 50 control workers were examined. After application of selection criteria 37 workers (mean age 43) exposed to Cd for an average of 11.3 years; and 43 age matched referents were retained for final analysis. The average concentrations of Cd in blood (Cd-B) and urine (Cd-U) of exposed workers were 5.5 micrograms Cd/l and 5.4 micrograms Cd/g creatinine respectively. By contrast with lead and mercury, Cd had a broad spectrum of effects on the kidney, producing significant alterations in amounts of almost all potential indicators of nephrotoxicity that were measured in urine--namely, low and high molecular weight proteins, kidney derived antigens or enzymes, prostanoids, and various other biochemical indices such as glycosaminoglycans and sialic acid. An increase in beta 2-microglobulin and a decrease of sialic acid concentration were found in serum. Dose-effect/response relations could be established between most of these markers and Cd-U or Cd-B. The thresholds of Cd-U associated with a significantly higher probability of change in these indicators were estimated by logistic regression analysis. Three main groups of thresholds could be identified: one around 2 micrograms Cd/g creatinine mainly associated with biochemical alterations, a second around 4 micrograms Cd/g creatinine for high molecular weight proteins and some tubular antigens or enzymes, and a third one around 10 micrograms Cd/g creatinine for low molecular weight proteins and other indicators. The recent recommendation by the American Conference of Governmental Industrial Hygienists (ACGIH) of 5 micrograms Cd/g creatinine in urine as the biological exposure limit for occupational exposure to Cd appears thus justified, although for most of the effects occurring around this threshold the link with the subsequent development of overt Cd nephropathy is not established. In that respect, the very early interference with production of some prostanoids (threshold 2 micrograms Cd/g creatinine) deserves further investigation; although this effect might contribute to protect the filtration capacity of the kidneys, it might also play a part in the toxicity of Cd on bone.

Adult↗
PubMed1992

Solid-phase extraction of prostanoids using an automatic sample preparation system.

A commercial automated solid-phase extraction system for cyclooxygenase arachidonic acid metabolites in urine samples has been evaluated. Comparison of manual and automatic batch (36 samples) extraction procedures for tritium labelled prostanoids added as tracers to urine samples has shown equivalent results with recoveries greater than 90% for prostaglandins E2, F2alpha and 6-keto prostaglandin F1alpha as well as thromboxane B2. Analyte stability is not affected by the automated procedure, which uses less solvents and has a faster overall processing time than the manual method. The automated system has been applied to the extraction of prostanoids in urine samples from workers exposed to dichloroethane.

Arachidonic Acids↗