ANA MARIA GONCALVES DA SILVA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina
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- 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(2018) BRAGANCA, Ana C. de; MOREAU, Regina L. M.; BRITO, Thales de; SHIMIZU, Maria H. M.; CANALE, Daniele; JESUS, Denise A. de; SILVA, Ana M. G.; GOIS, Pedro H.; SEGURO, Antonio C.; MAGALDI, Antonio J.
- 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(2017) BRAGANCA, Ana C. de; MOREAU, Regina L. M.; BRITO, Thales de; SHIMIZU, Maria H. M.; CANALE, Daniele; JESUS, Denise A. de; SILVA, Ana M. G.; GOIS, Pedro H.; SEGURO, Antonio C.; MAGALDI, Antonio J.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.
- Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis(2017) ABREU, Patricia A. E.; SEGURO, Antonio C.; CANALE, Daniele; SILVA, Ana Maria G. da; MATOS, Larissa do R. B.; GOTTI, Tatiane B.; MONARIS, Denize; JESUS, Denise A. de; VASCONCELLOS, Silvio A.; BRITO, Thales de; MAGALDI, Antonio J. B.Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo- or normokalemia. Higher serum potassium levels are observed in non-survivor patients and may have been caused by more severe AKI, metabolic disarrangement, or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level and maximum serum creatinine level has been observed in these patients, which suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32 and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but these proteins have no known function. This study evaluated the effect of these proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that appears responsible for the development of oliguric AKI associated with hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum phosphate). This study is the first characterization of a leptospiral outer membrane protein that is associated with severe manifestations of leptospirosis. Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced AKI could protect animals and patients from severe forms of this disease and decrease mortality.