title: Role of leukotriene B4 in accelerated hyperlipidaemic renal injury.
abstract: OBJECTIVE
  Glomerular infiltration of macrophages is a characteristic alteration of renal pathology in hyperlipidaemic renal injury. Leukotriene B4 (LTB4) is a bioactive eicosanoid and macrophage and has two key enzymes for LTB4 synthesis, 5-lipoxygenase and leukotriene A4 (LTA4) hydrolase. The purpose of this study was to evaluate the role of LTB4 in accelerated hyperlipidaemic renal injury.
  
  
  METHODS
  To induce accelerated hyperlipidaemic renal injury, 8 week old male spontaneously hypercholesterolaemic (SHC) rats were fed with a high cholesterol diet for 6 weeks. LTA4 hydrolase activities in the kidney and urine LTB4 levels were examined. The effects of LTB4 antagonist (ONO-4057) were also evaluated.
  
  
  RESULTS
  Urinary protein and LTB4 excretion was increased by a high cholesterol diet for 6 weeks. The scores of glomerular foam cell accumulation and sclerosis, numbers of infiltrated macrophages in glomeruli and interstitial area, LTA4 hydrolase activity in renal cortex were higher in the high cholesterol diet group than the normal diet group. LTB4 antagonist treatment reduced urinary protein and LTA4 activity and attenuated renal pathological changes.
  
  
  CONCLUSIONS
  These results suggest that LTB4 directly contributes to accelerated hyperlipidaemic renal injury and the therapeutic potential of LTB4 antagonist for renal damage induced by hyperlipidaemia.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tokyo Toshiba General Hospital, Tokyo, Japan. kdoi-tky@umin.ac.jp
authors.forename: Kent
authors.initials: K
authors.lastname: Doi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Eisei
authors.initials: E
authors.lastname: Noiri
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nosaka
authors.forename: Takako
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akiko
authors.initials: A
authors.lastname: Toda
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Akihide
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004195:Disease Models, Animal; D004851:Epoxide Hydrolases / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control / Q000652:urine; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000652:urine*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D051381:Rats; D013997:Time Factors
chemical_list: D020024:Leukotriene Antagonists; D010666:Phenylpropionates; C067523:ONO-LB 457; D007975:Leukotriene B4; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase