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Am J Trop Med Hyg ; 77(6): 1111-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18165532

ABSTRACT

Tubular dysfunction is a hallmark of severe leptospirosis. Antimicrobial therapy is thought to interfere on renal involvement. We evaluated the expression of a proximal tubule type-3 Na+/H+ exchanger (NHE3) and a thick ascending limb Na+-K+-2Cl(-) cotransporter (NKCC2) in controls and treated hamsters. Animals infected by a serovar Copenhageni isolate, were treated or not with ampicillin (AMP) and/or N-acetylcysteine (NAC). Leptospiral antigen(s) and expression of renal transporters were evaluated by immunohistochemistry, and serum thiobarbituric acid (TBARS) was quantified. Infected hamsters had high amounts of detectable leptospiral antigen(s) in target tissues while renal expression of NHE3 and NKCC2 decreased. Ampicillin treatment was associated with minimal or no detection of leptospiral antigens, normal expression of NHE3 and NKCC2 transporters, and reduced levels of TBARS. NAC effect was restricted to lowering TBARS. Early and late AMP treatment rescued tubular defects in severe leptospirosis disease, and there was no evidence of benefit from antioxidant therapy.


Subject(s)
Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Gene Expression Regulation/drug effects , Sodium-Hydrogen Exchangers/biosynthesis , Sodium-Potassium-Chloride Symporters/biosynthesis , Weil Disease/drug therapy , Acetylcysteine/administration & dosage , Acetylcysteine/pharmacology , Ampicillin/administration & dosage , Animals , Anti-Bacterial Agents/administration & dosage , Antigens, Bacterial/analysis , Cricetinae , Down-Regulation , Female , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/pharmacology , Gene Expression Profiling , Kidney/pathology , Kidney/physiopathology , Liver/pathology , Mesocricetus , Sodium-Hydrogen Exchanger 3 , Sodium-Hydrogen Exchangers/analysis , Sodium-Hydrogen Exchangers/drug effects , Sodium-Potassium-Chloride Symporters/analysis , Sodium-Potassium-Chloride Symporters/drug effects , Solute Carrier Family 12, Member 1 , Thiobarbiturates/blood , Weil Disease/pathology , Weil Disease/physiopathology
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