title: Reversal of renal tubule transporter downregulation during severe leptospirosis with antimicrobial therapy.
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.
authors.affiliation: Department of Nephrology, Laboratorio Pesquisa Basica LIM 12, Faculdade de Medicina USP, University of São Paulo School of Medicine, São Paulo, Brazil. annespichler@terra.com.br
authors.forename: Anne
authors.initials: A
authors.lastname: Spichler
authors.forename: Albert I
authors.initials: AI
authors.lastname: Ko
authors.forename: Everton Fagonde
authors.initials: EF
authors.lastname: Silva
authors.forename: Thales
authors.initials: T
authors.lastname: De Brito
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Silva
authors.forename: Daniel
authors.initials: D
authors.lastname: Athanazio
authors.forename: Cleiton
authors.initials: C
authors.lastname: Silva
authors.forename: Antonio
authors.initials: A
authors.lastname: Seguro
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology; D000667:Ampicillin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000032:analysis; D006224:Cricetinae; D015536:Down-Regulation; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000473:pathology; D008647:Mesocricetus; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D028021:Sodium-Potassium-Chloride Symporters / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D064466:Solute Carrier Family 12, Member 1; D013858:Thiobarbiturates / Q000097:blood; D014895:Weil Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D016166:Free Radical Scavengers; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D013858:Thiobarbiturates; D000667:Ampicillin; C029684:thiobarbituric acid; D000111:Acetylcysteine