Biomedical subjects

M C Souqual

Publications and source records attributed to M C Souqual.

7 recordsLinked to original sources

PubMed1991

Possible implication of arachidonic acid metabolism in the decrease of chemiluminescence production after exposure of murine peritoneal macrophages to diethylnitrosamine and tumour promoter, 12-O-tetradecanoylphorbol-13-acetate.

The effect of the carcinogen diethylnitrosamine (DEN) on prostaglandins (PGs), leukotrienes (LTs) and reactive oxygen intermediates production by murine peritoneal macrophages was assessed. In vitro exposure to DEN (0.8, 1.6 and 8 mM) resulted in a dose-dependent stimulation of the PGs and LTs generation by macrophages. DEN-exposed peritoneal macrophages demonstrated enhanced production of arachidonic acid (AA) metabolites following stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) as compared to macrophages stimulated with TPA alone. Studies of [3H]AA release from glycerolipids of prelabelled macrophages and of the distribution of AA metabolites between intra and extracellular compartments indicated that DEN induced de novo synthesis of AA metabolites. The stimulation of AA metabolism by DEN was decreased by H-7 and staurosporine, protein kinase C (PKC) inhibitors, and so could be dependent on PKC activation. The generation of PGs by macrophages after DEN exposure was also inhibited by indomethacin (cyclo-oxygenase inhibitor). DEN at high concentrations (1.6-16 mM) inhibited chemiluminescence production by peritoneal macrophages in a dose-dependent manner, triggered by tumour promoter TPA; lower concentrations (0.8 and 1.2 mM) increased this reactive oxygen intermediates dependent chemiluminescence production induced by TPA. The role of AA metabolism in the alteration of chemiluminescence production by murine peritoneal macrophages treated in vitro with DEN and triggered by TPA has been evaluated by using AA metabolism inhibitors. The stimulation of chemiluminescence by TPA was inhibited by the addition of phospholipase A2 (PLA2) inhibitor, 4-p-BPB; this metabolic inhibitor did not affect the decrease of chemiluminescence production induced by DEN. The cyclo-oxygenase (CO) inhibitor, indomethacin, reversed the inhibition of TPA-induced chemiluminescence caused by DEN. These results suggest that AA and/or a lipoxygenase product can potentiate the reactive oxygen intermediates production by macrophages stimulated by TPA. The CO pathway could be involved in the inhibition by DEN of the reactive oxygen intermediates generating enzyme system. It is suggested that this inhibition could be related to AA metabolites issued from the CO pathway or to DEN oxygenated metabolites issued from the co-oxidation of the DEN by the PGs endoperoxide synthase. These results also raise the problem of macrophage dysfunction by chemical carcinogens and the implication of the CO pathway in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

Systemic and splanchnic hemodynamic effects of molsidomine in rats with carbon tetrachloride-induced cirrhosis.

Molsidomine, a long-acting vasodilator mainly used as an antianginal agent, was reported to decrease the portohepatic venous pressure gradient in patients with alcoholic cirrhosis. This study investigated the effects of linsidomine, the active metabolite of molsidomine, on systemic and splanchnic hemodynamics in rats with CCl4-induced cirrhosis using the microsphere technique. Compared with placebo-treated rats, linsidomine-treated animals were found to have a significant decrease in portal venous pressure (-18%, p less than 0.01) and in mean arterial pressure (-16%, p less than 0.01), smaller peripheral resistances (p less than 0.01), greater portal venous inflow (p less than 0.05), smaller splanchnic arteriolar resistances (p less than 0.01) and smaller protocol-lateral resistances (p less than 0.05). Cardiac output, hepatic arterial blood flow, portal blood flow and estimated hepatic blood flow were not significantly different between the two groups of animals. Linsidomine-treated rats exhibited a trend toward greater collateral blood flow compared with controls, but this difference was not significant. We conclude that linsidomine decreases portal venous pressure by reducing portocollateral resistances without affecting liver blood flow. These effects should be beneficial for patients with cirrhosis and portal hypertension.

Animals↗

PubMed1990

1-naphthyl N-methyl carbamate effect on intra- and extracellular concentrations of arachidonic acid metabolites, and on the chemiluminescence generation by mouse peritoneal macrophages.

1-Naphthyl N-methyl carbamate (carbaryl), potent carbamate insecticide with anticholinesterase activity, was tested for its ability to affect mouse peritoneal macrophages in particular arachidonic acid (AA) metabolism and oxidative burst. Carbaryl inhibited in a dose-related manner the reactive oxygen intermediate dependent chemiluminescence (CL) induced by opsonized zymosan (OZ), 12-O-tetradecanoyl phorbol-13-acetate (TPA) and calcium ionophore (A23187); this carbamate did not affect CL-mediated by AA. The intracellular and extracellular concentrations of prostaglandins (PGs) and 5-hydroxyeicosatetraenoic (5-HETE) generated in macrophages stimulated with OZ has been investigated for various periods. Carbaryl effect displayed two successive phases on AA metabolism stimulation. In a first phase (up to 2-15 min), carbaryl did not alter the rapid AA metabolite synthesis (total amount of intra- and extracellular metabolites) but it increased intracellular concentration of PGE2, PGA2, PGF2 alpha and decreased 5-HETE intracellular concentration. In a second phase (after 2-15 min), carbaryl inhibited AA metabolite synthesis. The release of cyclooxygenase (CO) and lipoxygenase (LO) metabolites decreased, in particular PGF2 alpha and PGD2 which in addition seemed to be submit to a cellular retention; the inhibition of other metabolite release appeared essentially related to the inhibition of their synthesis since the intracellular amount did not augment. The inhibition by carbaryl of the NADPH-oxidase dependent CL induced by OZ may be related to the alteration of the intra- and extracellular concentrations of AA metabolites.

Animals↗

PubMed1990

Chemiluminescence response and arachidonic acid metabolism of macrophages induced by gamma-hexachlorocyclohexane (lindane).

The influence of gamma-hexachlorocyclohexane (gamma-HCCH) on arachidonic acid (AA) metabolism and oxygen metabolite production was investigated on mouse peritoneal macrophages gamma-HCCH stimulated 6KPGF1 alpha, PGE2, LTC4, LTB4 and HETEs production and increased the luminol-dependent chemiluminescence (CL). Lindane acted synergistically with phorbol ester on prostaglandins-leukotrienes (PGs-LTs) and CL production. Similar stimulation of CL and PGs-LTs production was found after challenge by the calcium ionophore A23187. The implication of calcium mobilization in lindane effects was proposed.

Animals↗

PubMed1989

In vitro influence of molybdenum on benzo[a]pyrene metabolism in hepatic and pulmonary rat microsomes.

Our study presents the in vitro molybdenum influence on benzo[a]pyrene (BaP) microsomal metabolism. Addition of various concentrations of different molybdenum salts [MoS2, MoCl5, (NH4)6Mo7O24 . 4H2O] to liver and lung microsomal fractions of rats previously treated with 3-methylcholanthrene produces a decrease in the different BaP metabolites assessed by high-performance liquid chromatography (HPLC) analysis. This inhibition varies, depending on the considered metabolite and in relation to both the molybdenum level and the origin of the microsomal suspension. The minimum effective concentration is 0.26 and 0.52 mM Mo from liver and lung, respectively. The inhibitory potencies of the +5 (chloride) and +6 (ammonium heptamolybdate) molybdenum compounds are comparable; that of the sulfide is lower.

Animals↗

PubMed1986

The effect of carbaryl on the arachidonic acid metabolism and superoxide production by mouse resident peritoneal macrophages challenged by zymosan.

Carbaryl, a broad spectrum insecticide with anticholinesterase activity, was tested for its ability to disturb resident peritoneal macrophages stimulated by opsonized zymosan. The effect of carbaryl on superoxide production and on the release of [1-14C] arachidonic acid and 14C-labelled prostaglandins was dose-dependent. For 2.5 X 10(-6) M of carbaryl, superoxide production and prostaglandin release were not significantly inhibited. At 12.5 X 10(-6) M, the inhibitory effect was apparent for superoxide production (33%) and for the release of 6 KPGF1 alpha (60%), PGE2 (42%), PGF2 alpha (38%), PGD2 (33%). Carbaryl had no effect on the level of free arachidonic acid. Insecticide at 12.5 X 10(-6) M significantly decreased the deacylation of the phosphatidylcholine (20%). Incubation of resident peritoneal macrophages with indomethacin studied conjointly decreased only the prostaglandin release. These results suggest that carbaryl decreases the sequence of events following the binding of a particulate agent to its receptor and leading to the induction of phospholipase activity and the subsequent release of 20:4 and the oxidative burst in the cells. The effect of this pesticide on phospholipid metabolism and its consequences on macrophage stimulation are discussed. Ecto-serine esterase inhibition in the effect mechanism of the pesticide was suggested.

Animals↗

PubMed1978

[Experimental inflammation after subchronic treatment with Nabam in the rat].

Inflammatory response to turpentine-induced granuloma components was studied in rats receiving 100 ppm Nabam (N,N'--ethylene--bis)dithiocarbamate) disodium) with food for one month. Results of nutritional, clinical and histopathological studies showed no modification. However, administration of Nabam modified the amounts of various mucopolysaccharides, which are important components of the inflammatory response; the amounts of total mucopolysaccharides, glucuronic acid mucopolysaccharides and sialic acid mucopolysaccharides were obviously lowered in treated animals, a symptom of impairment of the inflammatory response. When most classical means of investigation provide only little information, this test could allow toxicologists and nutritionists to evaluate the organisms reactivity to insidious toxic aggression.

Animals↗