Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP BRAGANCA, Ana C. de FMUSP-HC
MOREAU, Regina L. M.
JESUS, Denise A. de FMUSP-HC
MAGALDI, Antonio J. FMUSP-HC 2017
dc.identifier.citation PLOS ONE, v.12, n.7, article ID e0179199, 12p, 2017
dc.identifier.issn 1932-6203
dc.description.abstract Background Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. Methods Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). Results Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. Conclusion Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia.
dc.language.iso eng
dc.relation.ispartof Plos One
dc.rights openAccess
dc.subject.other mdma ecstasy; in-vitro; 3,4-methylenedioxymethamphetamine mdma; abuse; hyponatremia; temperature; ingestion; vasopressin; dysfunction; metabolism
dc.title Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage
dc.type article
dc.rights.holder Copyright PUBLIC LIBRARY SCIENCE LIM/12 LIM/06
dc.identifier.doi 10.1371/journal.pone.0179199
dc.identifier.pmid 28678861
dc.type.category original article
dc.type.version publishedVersion BRAGANCA, Ana C. de:HC:LIM/12 BRITO, Thales de:FM:MPT SHIMIZU, Maria H. M.:FM:MCM CANALE, Daniele:FM:MCM JESUS, Denise A. de:FM:MCM SILVA, Ana M. G.:HC:LIM/06 GOIS, Pedro H.:HC:LIM/12 SEGURO, Antonio C.:HC:ICHC MAGALDI, Antonio J.:HC:ICHC · MOREAU, Regina L. M.:Univ Sao Paulo, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, Sao Paulo, SP, Brazil WOS:000405272200008 2-s2.0-85022004305 SAN FRANCISCO USA
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