Design, Synthesis, Biological Evaluation, and Structure–Activity Relationships of Substituted Phenyl 4-(2-Oxoimidazolidin-1-yl)benzenesulfonates as New Tubulin Inhibitors Mimicking Combretastatin A-4

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Correction: 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.

[This corrects the article DOI: 10.1371/journal.pone.0179199.]

Representative light micrographs of Hematoxylin-Eosin stain.

<p>2a (Ec), 2b (Ec+NAC) and 2c (NAC+Ec) show areas of necrosis (*) and inflammatory infiltrations (macrophages)(arrows). 2d (Allo+Ec) shows no necrosis and slight inflammatory infiltration.</p

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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.).</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

Western-blot analysis of the water transporter.

<p>Bands 29 and 35-50kDa from AQP2. * p< 0.05 Li x Li+Ec.</p

Representative light micrographs of Hematoxylin-Eosin stain.

<p>2a (Ec), 2b (Ec+NAC) and 2c (NAC+Ec) show areas of necrosis (*) and inflammatory infiltrations (macrophages)(arrows). 2d (Allo+Ec) shows no necrosis and slight inflammatory infiltration.</p

Values of optic densitometry.

<p>Values of optic densitometry.</p

Values of TBARS and GSH.

<p>Values of TBARS and GSH.</p