title: Immunohistochemical expression of caspase-3, caspase-5, caspase-7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats exposed to zoledronic acid (ZOL) and basic fibroblast growth factor (bFGF).
abstract: BACKGROUND
  Bisphosphonates (BPs) like zoledronic acid (ZOL) are widely used for the treatment of different diseases such as osteoporosis, metastatic bone diseases and hypercalcaemia. However, the effects of BPs on apoptosis of the liver and kidney after treatment are unclear. Furthermore, basic fibroblast growth factor (bFGF) is an angiogenic molecule, which plays an important role in angiogenesis and tissue repair. The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF.
  
  
  OBJECTIVE
  The present study investigated the expression of caspase-3, -5, -7 and apoptotic protease-activating factor-1 (APAF-1) in the liver and kidney of rats treated with ZOL and bFGF.
  
  
  METHODS
  An animal model with 32 male Sprague Dawley rats was used. The effects of ZOL and bFGF on liver and kidney with the expressions of different apoptosis markers were studied histopathologically and immunohistochemically. Data were analyzed using Cronbach's alpha, Kruskal-Wallis and Bonnferroni-Dunn tests.
  
  
  RESULTS
  The main microscopic findings were mononuclear cell infiltrations around the bile ducts, binuclear and markedly enlarged hepatocytes (cytomegaly) and mitotic figures in the liver of rats treated with ZOL only. Immunohistochemically, both APAF-1 and caspase-3, -5 and -7 expressions were found elevated significantly (P < 0.05) in the liver and kidney of these rats.
  
  
  CONCLUSIONS
  Our findings showed that ZOL treatment increased while bFGF treatment decreased apoptosis significantly in the liver and kidney of Sprague Dawley rats.
  
  
  CONCLUSIONS
  The addition of bFGF to ZOL treatment of various diseases might reduce the ZOL effects.
authors.affiliation: a Department of Pathology, Faculty of Veterinary Medicine , Mehmet Akif Ersoy University , Burdur , Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Aydogan
authors.forename: Gulperi
authors.initials: G
authors.lastname: Kocer
authors.forename: Ozlem
authors.initials: O
authors.lastname: Ozmen
authors.forename: Murat
authors.initials: M
authors.lastname: Kocer
authors.forename: Levent
authors.initials: L
authors.lastname: Onal
authors.forename: Ozgur
authors.initials: O
authors.lastname: Koskan
mesh_terms: D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000378:metabolism*; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism*; D004164:Diphosphonates / Q000009:adverse effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D007093:Imidazoles / Q000009:adverse effects / Q000378:metabolism*; D007150:Immunohistochemistry / Q000662:veterinary; D007668:Kidney / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077211:Zoledronic Acid
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D005346:Fibroblast Growth Factors; D000077211:Zoledronic Acid; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases
keywords: apoptotic protease-activating factor-1; basic fibroblast growth factor; caspase; kidney; liver; rat; zoledronic acid