Biomedical subjects

M Joyeux

Publications and source records attributed to M Joyeux.

At least 19 recordsLinked to original sources

PubMed2001

2'-deoxyguanosine oxidation is associated with decrease in the DNA-binding activity of the transcription factor Sp1 in liver and kidney from diabetic and insulin-resistant rats.

Over the years, several lines of evidence have emerged supporting the role of oxidative stress in the development of diabetic complications. This could involve the increase in the production of reactive oxygen species and the decrease in antioxidative defense systems. Modulation of the level of intracellular reactive oxygen species is likely to affect the intracellular redox homeostasis, which is crucial for numerous biological events such as the transcriptional activation of genes. In this work we studied the binding of the redox transcription factors Sp1 and NF-kappaB extracted from kidney and liver of streptozotocin diabetic (STZ) and fructose-fed rats using electrophoretic mobility shift (EMSA) assay. In addition, the level in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) was assessed within DNA by high performance liquid chromatography with electrochemical detection (HPLC-EC). A decrease in the affinity of Sp1 to DNA was observed in the kidney of STZ rats and fructose-fed rats (15% +/- 8.3 and 54% +/- 6.9, respectively, versus control group set to 100%). This was also found to occur to a lower extent, in the liver. Interestingly, higher levels of 8-oxodGuo, a biomarker of DNA oxidation, were measured in the kidney of diabetic rats. Therefore, the modification in the binding efficiency of Sp1 or NF-kappaB could be related to reactive oxygen species-mediated DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Heat stress protects against electrophysiological damages induced by acute doxorubicin exposure in isolated rat hearts.

The use of anthracycline antibiotics as anticancer agents is limited by their cardiac toxicity. Heat stress (HS) is known to confer protection against various myocardial injuries such as ischemia-reperfusion induced damage. This cardioprotective mechanism is associated with an increase in endogenous antioxidative defenses and heat stress proteins (HSPs) synthesis. The aim of this study was thus to investigate whether HS could protect against acute doxorubicin cardiotoxicity using the isolated rat heart model. Rats were either heat stressed (42 degrees C for 15 min) or sham anesthetized. 24 h later, their hearts were isolated and retrogradely perfused at constant flow. Following 30-min of stabilization, hearts were perfused during 70 min with modified-Krebs solution containing 6 mg/l doxorubicin. Control hearts were perfused under identical conditions but without doxorubicin. Different hemodynamic and electrophysiological parameters were assessed in hearts from the four experimental groups. Doxorubicin exposure decreased left ventricular developed pressure (approximately -60% of baseline) and increased coronary perfusion pressure (approximately +230% of baseline). Prior HS did not modify these effects. Incidence of ventricular fibrillation (VF) was significantly enhanced by doxorubicin exposure (66% vs 0% in control group). Moreover, the ventricular action potential duration (APD) was significantly shortened in the presence of doxorubicin. Prior HS prevented both increase in VF incidence and shortening of APD. We conclude that prior heat stress protects myocardium against electrophysiological injury, but not against hemodynamic damage, induced by acute doxorubicine exposure. Further investigations are required to elucidate the precise mechanisms involved in this effect.

Animals↗

PubMed2001

Role of nitric oxide synthases in the infarct size-reducing effect conferred by heat stress in isolated rat hearts.

Nitric oxide (NO) donors are known to induce both delayed cardioprotection and myocardial heat stress protein (HSP) expression. Moreover, heat stress (HS), which also protects myocardium against ischaemic damages, is associated with a NO release. Therefore, we have investigated the implication of NO in HS-induced resistance to myocardial infarction, in the isolated rat heart model. Rats were divided in six groups (n=10 in each group), subjected or not to heat stress (42 degrees C internal temperature, 15 min) and treated or not with nitro-L-arginine-methylester (L-NAME) a non-selective inhibitor of NO synthase isoforms, or L-N(6)-(1-imino-ethyl)lysine (L-NIL), a selective inhibitor of the inducible NO synthase. Twenty-four hours after heat stress, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Infarct-to-risk ratio was significantly reduced in HS (18.7+/-1.6%) compared to Sham (33.0+/-1.7%) hearts. This effect was abolished in L-NAME-treated (41.7+/-3.1% in HS+L-NAME vs 35.2+/-3.0% in Sham+L-NAME ) and L-NIL-treated (36.1+/-3.4% in HS+L-NIL vs 42.1+/-4.6% in Sham+L-NIL) groups. Immunohistochemical analysis of myocardial HSP 27 and 72 showed an HS-induced increase of these proteins, which was not modified by L-NAME pretreatment. We conclude that NO synthases, and in particular the inducible isoform, appear to play a role in the heat stress-induced cardioprotection, independently of HSP 27 and 72 levels. Further investigations are required to elucidate the precise role of HSPs in this adaptive response.

Animals↗

PubMed2000

Genotoxic activity of five haloacetonitriles: comparative investigations in the single cell gel electrophoresis (comet) assay and the ames-fluctuation test.

Halogenated acetonitriles (HANs) are known to be water disinfectant by-products. Their mutagenicity and carcinogenicity have been shown in different test systems in vivo and in vitro. They also have clastogenic properties. In this study, the ability of HAN to induce single-strand breaks on the DNA of HeLa S3 cells was investigated using the single-cell gel electrophoresis (SCGE) assay, which could be a good tool with which to evaluate the genotoxicity of chlorinated water. The results were compared to those obtained in the Ames fluctuation test using the Salmonella typhimurium TA 100 strain without activation. With the Ames fluctuation test, a mutagenic effect was observed for chloroacetonitrile (MCAN), dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). No mutagenic effect was found with bromoacetonitrile (MBAN) or dibromoacetonitrile (DBAN). In the SCGE assay, all five HANs induced DNA damage in HeLa S3 cells, increasing the mean tail moment significantly. For each compound, a dose-effect relation was observed. This study shows that the SCGE assay has greater sensitivity for assessing the genotoxicity of HAN than does the Ames-fluctuation test. Brominated acetonitriles were more genotoxic than chlorinated acetonitriles in the SCGE assay, and the genotoxicity increased with the number of halogenated atoms of the compound. This behavior had already been found with other genotoxicity tests.

Acetonitriles↗

PubMed2000

Protective effects of melatonin against ischemia-reperfusion injury in the isolated rat heart.

There has been increased interest in melatonin recently, since it was shown to be a potent scavenger of toxic free radicals. Melatonin has been found to be effective in protecting against pathological states due to reactive oxygen species release. The present study was performed in order to determine whether melatonin or 5-methoxy-carbonylamino-N-acetyl-tryptamine (5-MCA-NAT), a structurally related indole compound, protect against ischemia-reperfusion injury in the isolated rat heart. Wistar rats were treated in vivo with either melatonin (1 or 10 mg/kg, i.p.) or 5-MCA-NAT (10 mg/kg, i.p.) or their vehicle, 30 min before their hearts were excised and perfused according to the Langendorff technique. Two different protocols were then applied. In the first one, a regional ischemia (5 min)-reperfusion (30 min) sequence was performed in order to record incidence and duration of reperfusion arrhythmias. In the second one, infarct size was assessed after a regional ischemia (30 min)-reperfusion (120 min) sequence. Results show a spectacular protection against ischemia-reperfusion injuries (on arrhythmias as well as on infarct size) in rats pre-treated with 10 mg/kg of melatonin or 5-MCA-NAT. In conclusion, both melatonin and its structural analog, 5-MCA-NAT, appear to confer protection against ischemia-reperfusion injury in the isolated rat heart. This observation suggests that melatonin could have a potential clinical application in the treatment of myocardial ischemia, even if the mechanisms underlying this protection remain to be determined.

Animals↗

PubMed2000

Effect of okadaic acid, a protein phosphatase inhibitor, on heat stress-induced HSP72 synthesis and thermotolerance.

Heat stress proteins (HSPs), in particular HSP72, seem to play a major role in cell protection against lethal stresses such as hyperthermia or ischemia. HSP synthesis is negatively regulated by protein phosphatases, which are implicated in dephosphorylation processes. In the present study, we have investigated the effect of okadaic acid (OA, a protein phosphatase inhibitor) on heat stress-induced HSP72 synthesis and thermotolerance in smooth muscle cells (SMC). SMC were heat stressed (42 degrees C for 20 minutes) in the presence of 250 nM OA (HS+OA cells) or its vehicle (HS+V cells). Control (OA or V) cells were not heat stressed. HSP72 mRNA expression was determined 1, 1.5, 3, and 6 hours after heat stress by RT-PCR, and HSP72 synthesis was determined 6, 12, 24, 48, and 72 hours after heat stress by Western blotting. SMC survival of lethal hyperthermia (47 degrees C for 90 minutes) was assessed 6, 24, and 48 hours after heat stress by a tetrazolium assay. The maximal expression of HSP72 mRNA was markedly prolonged in HS+OA cells (until 6 hours after heat stress) compared to HS+V cells (1 hour after heat stress). The kinetics of HSP72 synthesis and thermotolerance of SMC were not different between HS+OA and HS+V cells. Baseline HSP72 mRNA and protein expression were similar in control V and OA cells. In conclusion, okadaic acid treatment of SMC potentiated HSP72 mRNA expression without affecting heat stress-induced HSP72 synthesis and thermotolerance.

Animals↗

PubMed2000

SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to myocardial infarction induced by heat stress.

Heat stress (HS) is known to confer protection against ischemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the mechanisms involved in this cardioprotection are yet to be elucidated. Mitogen-activated protein (MAP) kinase cascades have been demonstrated to be involved in cellular response to different stresses. In particular, p38 MAP kinase is known to be activated by HS. Therefore, we investigated the implication of this kinase in HS-induced resistance to myocardial infarction, in the isolated rat heart model, using SB 203580 (SB) to selectively inhibit p38 MAP kinase. Rats were treated with SB (2.83 mg/kg, i.p.) or vehicle (1% DMSO in saline, i.p.) before they were either heat stressed (42 degrees C for 15 minutes) or sham anesthetized. Their hearts were isolated 24 hours later, retrogradely perfused, and subjected to a 35-minute occlusion of the left coronary artery followed by 120 minutes of reperfusion. The infarct-to-risk ratio was significantly reduced in HS (16.9 +/- 2.0%) compared with sham (41.6 +/- 2.5%) hearts. This reduction in infarct size was abolished in the SB 203580-treated group (37.8 +/- 1.9% in HS + SB vs. 42.0 +/- 1.9% in sham + SB). Risk zones were similar between experimental groups. Western blot analysis of the myocardial HSP72 showed an HS-induced increase of this protein, which was not modified by the p38 MAP kinase inhibitor, SB 203580. We conclude that activation of p38 MAP kinase appears to play a role in the functional cardioprotection associated with the heat stress response, which seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the p38 MAP kinase and heat stress proteins in this adaptative response.

Animals↗

PubMed2000

Heat stress-induced protection of endothelial function against ischaemic injury is abolished by ATP-sensitive potassium channel blockade in the isolated rat heart.

The protection conferred by heat stress (HS) against myocardial ischaemia-reperfusion injury, in terms of mechanical function preservation and infarct size reduction, is well documented and mechanisms underlying these effects have been extensively explored. However, the effect of HS on coronary circulation is less known. The aim of this study was thus to investigate the role of ATP-sensitive potassium (K(ATP)) channels in the protection against ischaemic injury afforded by HS to the coronary endothelial function. Twenty-four hours after whole body hyperthermia (42 degrees C for 15 min, H groups) or sham anaesthesia (Sham groups), isolated perfused rat hearts were subjected to a 15 min stabilization period followed by a 30 min infusion of either 0.3 microM glibenclamide (Gli, a K(ATP) channel blocker) or its vehicle (V). Hearts were then exposed to a low-flow ischaemia (30 min)-reperfusion (20 min) (I/R) or normally perfused (50 min), after which coronaries were precontracted with 0.1 microM U-46619. Finally, the response to the endothelium-dependent vasodilator, 5-hydroxytryptamine (5-HT, 10 microM) was compared to that of the endothelium-independent vasodilator, sodium nitroprusside (SNP, 3 microM). In hearts from Sham-V and Sham-Gli groups, I/R selectively diminished 5-HT-induced vasodilatation without affecting the vasodilatation to SNP. In V-treated groups, prior HS preserved the vasodilatation produced by 5-HT. This HS-induced protection was abolished by Gli treatment. In conclusion, these results suggest that K(ATP) channel activation contributes to the preservation of coronary endothelial function conferred by heat stress against ischaemic insult.

ATP-Binding Cassette Transporters↗

PubMed2000

In vitro and in vivo studies on chelation of manganese.

This work deals with new chelating agents of manganese (Mn). Out of 24 compounds chosen for their chemical structure supposed to be favorable for Mn complexation, six polyaminopolycarboxylic acids proved to be efficient for displacing Mn bound to serum bovine proteins in vitro: TTHA, DTPA, DPTA, DPTA-OH, HBED, EDTA (mobilization > or =50%). The first five compounds were then tested in vivo on rats pretreated with MnCl2. They exhibited only slight to moderate efficacy to diminish Mn in tissues and were ineffective on increased Mn concentration in whole blood; in addition, they had different and specific mobilizing effects on other essential elements (Fe, Zn, Cu). Their limited efficacy in vivo could be due to the formation of very stable complexes between Mn2+ and different molecules such as hemoglobin and certain cytochromes, instead of Fe2+. This could disturb the functioning of the cellular respiratory chain, leading to an incomplete reduction of O2 with formation of free oxygenated radicals, reduction in the energy supply, and disturbance of the cytochromes renewal mechanism. All of these phenomena could accelerate cellular aging and explain the lack of efficacy of the chelating agents towards Mn neurotoxicity (Parkinson's syndrome).

Animals↗

PubMed2000

Nickel absorption and distribution from rat small intestine in situ.

The aim of this work was to study the absorption of nickel chloride in rats by means of the intestinal perfusion in situ technique at nickel concentrations of 1, 5, 10, 25, and 100 mg/L. Active transport and facilitated diffusion seem to play an important role in the intestinal absorption of nickel at concentrations < or = 10 mg/L. At higher concentrations, the absorption rate would be limited by saturation of the carriers. The distribution of the absorbed nickel was studied by intestinal perfusion of a 10-mg Ni/L solution for 30 or 60 min. Both in concentration and amount, the jejunum showed the higher values of absorbed nickel, followed by the kidneys and liver. When all of the collected organs (brain, heart, liver, lungs, spleen, kidneys, and testicles) and blood, but not the small intestine, are analyzed following a 60-min perfusion, it was found that 1% of the initial concentration had passed through the intestinal barrier.

Animals↗

PubMed2000

Bioavailability and intestinal absorption of aluminum in rats: effects of aluminum compounds and some dietary constituents.

In the present investigation, the deposition of aluminum in intestinal fragment and the appearance in blood were studied in a perfused rat intestine in situ for 1 h with several aluminum forms (16 mM). We observed that aluminum absorption was positively correlated with the theoretic affinity of aluminum and the functional groups of the chelating agent. The absorption of aluminum after ingestion of organic compounds is more important than after ingestion of mineral compounds, with the following order: Al citrate > Al tartrate, Al gluconate, Al lactate > Al glutamate, Al chloride, Al sulfate, Al nitrate. Absorption depends on the nature of the ligands associated with the Al3+ ion in the gastrointestinal fluid. The higher the aluminum retention in intestinal fragment, the lower the absorption and appearance in blood. However, the higher aluminum concentration is always in the jejunal fragment because of the influence of pH variation on this fragment. Another objective of the present study was to determine the influence of several parameters on aluminum citrate absorption: with or without 0.1 mmol dinitrophenol/L, with aluminum concentration from 3.2, 16, 32, and 48, to 64 mmol/L, media containing 0, 3, or 6 mmol Ca/L, with or without phosphorus or glucose. It is concluded that aluminum is absorbed from the gastrointestinal tract by (1) a paracellular energy independent and nonsaturable route, mainly used for high aluminum concentration, which is modified by extracellular calcium, and (2) a transcellular and saturable route, the aluminum level was not modified with enhancement of aluminum quantity in intestinal lumen. This pathway can be similar with calcium transfer through the intestine and is energy dependent because of a decrease of aluminum absorption that follows the removal of glucose and phosphorus.

Alum Compounds↗

PubMed1999

Behavioral evaluation of visceral pain in a rat model of colonic inflammation.

A new rat model was established up to evaluate the antinociceptive effect of compounds in visceral pain. The test consisted in measuring the performance of rats in an aversive light stimulus avoidance experimental device. Rats with TNBS-induced colitis had a lower number of total active lever pressings and did not discriminate the active lever from the inactive one. Morphine (1 mg/kg, s.c.) and CI-977 (0.001 mg/kg, s.c.) treatment restored the level of pressing activity of animals and their ability to discriminate the active lever from the inactive one. Naloxone treatment antagonized the improvement of performance produced by morphine. The results obtained indicate that this behavioral paradigm may be used to evaluate the antinociceptive potential of compounds.

Analgesics, Opioid↗

PubMed1999

Determination of dietary tin intake in an adult French citizen.

The tin contents in fresh food or in food stored in lacquered or unlacquered cans were determined in order to estimate the daily tin intake in a French citizen. Tin levels were 76.6 +/- 36.5 mg/kg in foods preserved in unlacquered cans, 3.2 +/- 2.3 mg/kg in foods stored in lacquered cans, and 0.03 +/- 0.03 mg/kg in fresh foods. Tin intake is essentially dependent on food stored in tin cans (98%), which only represents 5.6% of the total daily consumption of foods by a French citizen. The estimated tin intake (2.7 mg/day whether 0. 04 mg/kg of body weight) remains widely inferior to the daily tolerable dose in humans (2 mg/kg of body weight).

Adult↗

PubMed1999

Heat stress fails to protect myocardium of streptozotocin-induced diabetic rats against infarction.

OBJECTIVE: Protection conferred by heat stress (HS) against ischaemia-reperfusion injury, in term of mechanical function and myocardial necrosis, has been extensively studied. In contrast, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated heart and on the myocardial heat stress protein (HSP) 72 synthesis, in a model of insulin-dependent diabetic rats. METHODS: Three groups of animals were studied: D rats were rendered diabetic by 55 mg/kg streptozotocin i.v. injection. DI rats received the same treatment plus a daily injection of insulin started 2 weeks after and V rats received the vehicle of streptozotocin plus a daily injection of saline. Eight weeks later, D, DI and V rats were either heat-stressed (42 degrees C for 15 min) or sham-anaesthetised. Twenty-four hours later, their hearts were isolated, perfused using the Langendorff technique, and subjected to a 30 min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using an electrophoresis coupled with a Western blot analysis. RESULTS: Infarct-to-risk ratio (I/R) was significantly reduced in hearts from heat-stressed (11.7 +/- 2.0%) compared to sham (30.0 +/- 3.2%) V rats. This cardioprotection was not observed in hearts from D (I/R: 31.4 +/- 3.3 vs. 34.3 +/- 3.5%) and DI (I/R: 28.7 +/- 1.6 vs. 30.3 +/- 1.6%) rats. Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the six experimental groups. Western blot analysis of the myocardial HSP72 content showed a comparable heat stress-induced increase of this protein, in V, D and DI animals. CONCLUSION: These results demonstrate that myocardial protective effect induced by heat stress could not extend to a pathological animal model like the diabetic rat and seems to be unrelated to the HSP72 level. Further investigations are required to elucidate the precise role of the heat stress proteins in this adaptive response.

Analysis of Variance↗

PubMed1999

Heat stress response and myocardial protection.

Prior whole-body hyperthermia is able to protect the myocardium against ischaemia-reperfusion injury by reducing cellular necrosis, preserving the ventricular function and preventing the occurrence of arrhythmias. These cardioprotective effects are associated with reduction of oxidative stress, preservation of the high-energy phosphate levels and synthesis of heat stress proteins. A better understanding of this powerful protective adaptation of the myocytes would be of interest for potential clinical application, and rational design of specific agents that activate this mechanism will hopefully follow soon.

Animals↗

PubMed1998

Daily intake of essential minerals and metallic micropollutants from foods in France.

Daily intakes of essential minerals and metallic micro-pollutants are estimated from foods usually eaten in France. These foods are grouped in nine categories. For essential elements, intake estimates are comparable to the values recommended by the WHO. The cadmium value is lower than the tolerable daily dose. The estimated values are: cobalt 29 micrograms/day, chromium 98 microgram/day, copper 1.5 mg/day, manganese 2.5 mg/day, molybdenum 275 micrograms/day, zinc 14 microgram/day, aluminium 4.2 mg/day, boron 1.6 mg/day, cadmium 27 micrograms/day and nickel 231 microgram/day.

Diet↗

PubMed1998

Heat stress-induced resistance to myocardial infarction in the isolated heart from transgenic [(mREN-2)27] hypertensive rats.

OBJECTIVE: Heat stress (HS) is known to confer protection against ischaemia-reperfusion injury, including mechanical dysfunction and myocardial necrosis. However, the effects of disease states on this HS-induced cytoprotective response are less known. Therefore, we investigated the effects of prior heat stress on the infarct size in the isolated rat heart and on the myocardial heat stress protein (HSP) 72 synthesis, in transgenic [(mREN-2)27] hypertensive (TGH) rats or normotensive (NT) controls. METHODS: TGH or NT rats were either heat stressed (42 degrees C for 15 min) or sham anaesthetised. After 24 h, their hearts were isolated, perfused using the Langengorff technique, and subjected to a 35-min occlusion of the left coronary artery followed by 120 min of reperfusion. Myocardial HSP72 content was measured 24 h after HS or sham treatment using electrophoresis coupled with Western blot analysis. RESULTS: Infarct-to-risk (I/R) ratio was significantly reduced in HS (15.5 +/- 1.2%) compared to sham (42.2 +/- 2.1%) hearts of NT rats. This reduction in infarct size was maintained in TGH hearts (I/R: 20.0 +/- 1.0 vs. 48.0 +/- 3.8%). Risk zones were similar between all experimental groups. The incidence of ventricular arrhythmias during ischaemia and reperfusion periods was not different between the four experimental groups. Western blot analysis of the myocardial HSP72 content showed a heat stress-induced increase of this protein, in both TGH and NT animals. CONCLUSION: These results demonstrate that the myocardial protective effect induced by heat stress could extend to a pathological animal model like the transgenic [(mREN-2)27] hypertensive rat and is correlated with a myocardial HSP72 induction.

Analysis of Variance↗

PubMed1998

Resistance to myocardial infarction induced by heat stress and the effect of ATP-sensitive potassium channel blockade in the rat isolated heart.

1. Heat stress (HS) is known to protect against myocardial ischaemia-reperfusion injury by improving mechanical dysfunction and decreasing necrosis. However, the mechanisms responsible for this form of cardioprotection remain to be elucidated. ATP-sensitive potassium (K(ATP)) channels have been shown to be involved in the delayed phase of protection following ischaemic preconditioning, a phenomenon closely resembling the HS-induced cardioprotection. The aim of this study was thus to investigate the role of K(ATP) channels in HS-induced protection of the isolated rat heart. 2. Twenty four hours after whole body heat stress (at 42 degrees C for 15 min) or sham anaesthesia, isolated perfused hearts were subjected to a 15 min stabilization period followed by a 15 min infusion of either 10 microM glibenclamide (Glib), 100 microM sodium 5-hydroxydecanoate (5HD) or vehicle (0.04% DMSO). Regional ischaemia (35 min) and reperfusion (120 min) were then performed. 3. Prior heat stress significantly reduced infarct-to-risk ratio (from 42.4+/-2.4% to 19.4+/-2.9, P<0.001). This resistance to myocardial infarction was abolished in both Glib-treated (40.1+/-1.8% vs 42.3+/-1.8%) and 5HD-treated (41.2+/-1.8% vs 41.8+/-1.2%) groups. 4. The results of this study suggest that K(ATP) channel activation contributes to the cytoprotective response induced by heat stress.

Animals↗