1. Role of leukotriene B4 in accelerated hyperlipidaemic renal injury.
- Author
-
Doi K, Hamasaki Y, Noiri E, Nosaka K, Suzuki T, Toda A, Shimizu T, Fujita T, and Nakao A
- Subjects
- Animals, Blood Pressure, Body Weight, Disease Models, Animal, Epoxide Hydrolases metabolism, Foam Cells metabolism, Hypercholesterolemia drug therapy, Hypercholesterolemia pathology, Hypercholesterolemia physiopathology, Hypercholesterolemia urine, Kidney Diseases pathology, Kidney Diseases physiopathology, Kidney Diseases prevention & control, Kidney Diseases urine, Kidney Glomerulus drug effects, Kidney Glomerulus pathology, Kidney Glomerulus physiopathology, Leukotriene Antagonists pharmacology, Leukotriene B4 antagonists & inhibitors, Male, Phenylpropionates pharmacology, Proteinuria etiology, Proteinuria urine, Rats, Time Factors, Hypercholesterolemia complications, Kidney Diseases etiology, Kidney Glomerulus metabolism, Leukotriene B4 urine
- Abstract
Aim: 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., Conclusion: 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., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)
- Published
- 2011
- Full Text
- View/download PDF