title: Previous exposure to cigarette smoke aggravates experimental cyclosporine-induced nephrotoxicity.
abstract: OBJECTIVE
  The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity.
  
  
  METHODS
  Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal α-smooth muscle actin (SMA), nitrotyrosine, and vimentin.
  
  
  RESULTS
  CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular α-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and α-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure.
  
  
  CONCLUSIONS
  CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity.
authors.affiliation: Division of Nephrology, São Jose do Rio Preto Medical School, São Jose do Rio Preto, Brazil.
authors.forename: Sueli A
authors.initials: SA
authors.lastname: Alves
authors.forename: Carla P
authors.initials: CP
authors.lastname: Carlos
authors.forename: Glória E F
authors.initials: GE
authors.lastname: Mendes
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Marcus A M
authors.initials: MA
authors.lastname: Luz
authors.forename: Rafael P S
authors.initials: RP
authors.lastname: Souza
authors.forename: Rael L
authors.initials: RL
authors.lastname: Matimoto
authors.forename: Terezila M
authors.initials: TM
authors.lastname: Coimbra
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Burdmann
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000009:adverse effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D014443:Tyrosine; D014746:Vimentin; C498862:Acta2 protein, rat; C002744:3-nitrotyrosine