Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat
Identifieur interne : 000159 ( France/Analysis ); précédent : 000158; suivant : 000160Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat
Auteurs : Magali Chautan [France] ; Jeannie Leonardi [France] ; Raymond Calaf [France] ; Paulette Lechene [France] ; Renée Grataroli [France] ; Henri Portugal [France] ; Anne-Marie Pauli [France] ; Huguette Lafont [France] ; Gilles Nalbone [France]Source :
- Biochemical Pharmacology [ 0006-2952 ] ; 1992.
English descriptors
- KwdEn :
- ACLAT, CE, DOX, EPI, GSH-PX, GSH-T, MIT, PIR, PUFA, TBARS, TC, TG, UC, acyl-CoA, cholesteryl ester, doxorubicin, epirubicin, glutathione S-transferases, lysophosphatidylcholine acyltransferase, mitoxantrone, pirarubicin, polyunsaturated fatty acids, selenium-dependent glutathione peroxidase, thiobarbituric acid reactive substances, total cholesterol, triglycerides, unesterified cholesterol.
Abstract
The purpose of this study was to investigate in the rat heart and liver the effects of an acute administration of three anthracyclines, doxorubicin, epirubicin and pirarubicin, and an anthracenedione, mitoxantrone, on the membrane peroxidative status, which was estimated by the composition of polyunsaturated fatty acids (PUFA), and on the activities of the enzymes involved in membrane repair processes and lipid hydroperoxide detoxification. Rats were injected for four consecutive days with the drugs or saline (control) and killed 24 hr after the last injection. All the drugs induced an increase in plasma thiobarbituric reactive substances and α-tocopherol concentrations, both expressed per milligram of plasma lipids. Plasma vitamin A was decreased by about a factor of two by all the drugs. The fatty acid profile in the heart lipids showed that the polyunsaturated species (20:4 n-6, 22:6 n-3) remained at the same or even higher levels after anthracycline treatment. This can be explained by the fact that the activities of the enzymes involved in either the recycling of membrane phospholipids, such as phospholipases A1 and A2 (EC 3.1.1.4 and EC 3.1.1.32), lysophospholipases (EC 3.1.1.5) and acylCoA:lysophosphatidylcholine acyltransferases (EC 2.3.1.23), or hydroperoxide detoxification, such as selenium-dependent glutathione peroxidase (GSH-PX, EC 1.11.1.9) and glutathione S-transferases (GSH-T, EC 2.1.5.18), were maintained at the same level of activity after the antitumoral treatment. In liver, membrane phospholipid levels of PUFA were maintained as well as the activities of phospholipidmetabolizing enzymes. GSH-PX activity was not affected whereas that of GSH-T was slightly lowered by the drugs. These results suggest that during acute antitumoral-induced lipid peroxidation of membranes, the multi-enzymatic complex of the immediate processes of repair and detoxification is fully operational, allowing the membrane to rapidly recover its functional status. The results are discussed in the context of the equivocal relationships between antitumoral-induced lipid peroxidation and cardiac disturbances.
Url:
DOI: 10.1016/0006-2952(92)90378-V
Affiliations:
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ISTEX:34D8DB4D6A158325BFB1D80F6DAD24F042BEFD2DLe document en format XML
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type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Leonardi, Jeannie" sort="Leonardi, Jeannie" uniqKey="Leonardi J" first="Jeannie" last="Leonardi">Jeannie Leonardi</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 130, 18 Avenue Mozart, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Calaf, Raymond" sort="Calaf, Raymond" uniqKey="Calaf R" first="Raymond" last="Calaf">Raymond Calaf</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie, Faculté de Pharmacie, 13005 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Lechene, Paulette" sort="Lechene, Paulette" uniqKey="Lechene P" first="Paulette" last="Lechene">Paulette Lechene</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 130, 18 Avenue Mozart, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Grataroli, Renee" sort="Grataroli, Renee" uniqKey="Grataroli R" first="Renée" last="Grataroli">Renée Grataroli</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Central, Hôpital Ste-Marguerite, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Portugal, Henri" sort="Portugal, Henri" uniqKey="Portugal H" first="Henri" last="Portugal">Henri Portugal</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Central, Hôpital Ste-Marguerite, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Pauli, Anne Marie" sort="Pauli, Anne Marie" uniqKey="Pauli A" first="Anne-Marie" last="Pauli">Anne-Marie Pauli</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Central, Hôpital Ste-Marguerite, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Lafont, Huguette" sort="Lafont, Huguette" uniqKey="Lafont H" first="Huguette" last="Lafont">Huguette Lafont</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 130, 18 Avenue Mozart, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Nalbone, Gilles" sort="Nalbone, Gilles" uniqKey="Nalbone G" first="Gilles" last="Nalbone">Gilles Nalbone</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM Unité 130, 18 Avenue Mozart, 13009 Marseille</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation><affiliation><wicri:noCountry code="no comma">Corresponding author. Tel (33) 91 75 47 05 or 91 74 23 00; FAX (33)91 75 15 62.</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j">Biochemical Pharmacology</title><title level="j" type="abbrev">BCP</title><idno type="ISSN">0006-2952</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1992">1992</date><biblScope unit="volume">44</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1139">1139</biblScope><biblScope unit="page" to="1147">1147</biblScope></imprint><idno type="ISSN">0006-2952</idno></series><idno type="istex">34D8DB4D6A158325BFB1D80F6DAD24F042BEFD2D</idno><idno type="DOI">10.1016/0006-2952(92)90378-V</idno><idno type="PII">0006-2952(92)90378-V</idno><idno type="ArticleID">9290378V</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-2952</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ACLAT</term><term>CE</term><term>DOX</term><term>EPI</term><term>GSH-PX</term><term>GSH-T</term><term>MIT</term><term>PIR</term><term>PUFA</term><term>TBARS</term><term>TC</term><term>TG</term><term>UC</term><term>acyl-CoA</term><term>cholesteryl ester</term><term>doxorubicin</term><term>epirubicin</term><term>glutathione S-transferases</term><term>lysophosphatidylcholine acyltransferase</term><term>mitoxantrone</term><term>pirarubicin</term><term>polyunsaturated fatty acids</term><term>selenium-dependent glutathione peroxidase</term><term>thiobarbituric acid reactive substances</term><term>total cholesterol</term><term>triglycerides</term><term>unesterified cholesterol</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The purpose of this study was to investigate in the rat heart and liver the effects of an acute administration of three anthracyclines, doxorubicin, epirubicin and pirarubicin, and an anthracenedione, mitoxantrone, on the membrane peroxidative status, which was estimated by the composition of polyunsaturated fatty acids (PUFA), and on the activities of the enzymes involved in membrane repair processes and lipid hydroperoxide detoxification. Rats were injected for four consecutive days with the drugs or saline (control) and killed 24 hr after the last injection. All the drugs induced an increase in plasma thiobarbituric reactive substances and α-tocopherol concentrations, both expressed per milligram of plasma lipids. Plasma vitamin A was decreased by about a factor of two by all the drugs. The fatty acid profile in the heart lipids showed that the polyunsaturated species (20:4 n-6, 22:6 n-3) remained at the same or even higher levels after anthracycline treatment. This can be explained by the fact that the activities of the enzymes involved in either the recycling of membrane phospholipids, such as phospholipases A1 and A2 (EC 3.1.1.4 and EC 3.1.1.32), lysophospholipases (EC 3.1.1.5) and acylCoA:lysophosphatidylcholine acyltransferases (EC 2.3.1.23), or hydroperoxide detoxification, such as selenium-dependent glutathione peroxidase (GSH-PX, EC 1.11.1.9) and glutathione S-transferases (GSH-T, EC 2.1.5.18), were maintained at the same level of activity after the antitumoral treatment. In liver, membrane phospholipid levels of PUFA were maintained as well as the activities of phospholipidmetabolizing enzymes. GSH-PX activity was not affected whereas that of GSH-T was slightly lowered by the drugs. These results suggest that during acute antitumoral-induced lipid peroxidation of membranes, the multi-enzymatic complex of the immediate processes of repair and detoxification is fully operational, allowing the membrane to rapidly recover its functional status. The results are discussed in the context of the equivocal relationships between antitumoral-induced lipid peroxidation and cardiac disturbances.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Chautan, Magali" sort="Chautan, Magali" uniqKey="Chautan M" first="Magali" last="Chautan">Magali Chautan</name></region><name sortKey="Calaf, Raymond" sort="Calaf, Raymond" uniqKey="Calaf R" first="Raymond" last="Calaf">Raymond Calaf</name><name sortKey="Grataroli, Renee" sort="Grataroli, Renee" uniqKey="Grataroli R" first="Renée" last="Grataroli">Renée Grataroli</name><name sortKey="Lafont, Huguette" sort="Lafont, Huguette" uniqKey="Lafont H" first="Huguette" last="Lafont">Huguette Lafont</name><name sortKey="Lechene, Paulette" sort="Lechene, Paulette" uniqKey="Lechene P" first="Paulette" last="Lechene">Paulette Lechene</name><name sortKey="Leonardi, Jeannie" sort="Leonardi, Jeannie" uniqKey="Leonardi J" first="Jeannie" last="Leonardi">Jeannie Leonardi</name><name sortKey="Nalbone, Gilles" sort="Nalbone, Gilles" uniqKey="Nalbone G" first="Gilles" last="Nalbone">Gilles Nalbone</name><name sortKey="Pauli, Anne Marie" sort="Pauli, Anne Marie" uniqKey="Pauli A" first="Anne-Marie" last="Pauli">Anne-Marie Pauli</name><name sortKey="Portugal, Henri" sort="Portugal, Henri" uniqKey="Portugal H" first="Henri" last="Portugal">Henri Portugal</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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