Ergosta-4,6,8(14),22-tetraen-3-one isolated from Polyporus umbellatus prevents early renal injury in aristolochic acid-induced nephropathy rats

• Published in: Journal of pharmacy and pharmacology 2011-12, Vol.63 (12), p.1581-1586
• Main Authors: Zhao, Ying-Yong, Zhang, Li, Mao, Jia-Rong, Cheng, Xiao-Hong, Lin, Rui-Chao, Zhang, Yongmin, Sun, Wen-Ji
• Format: Article
• Language: English
• Subjects: 22-tetraen-3-one; Acute Kidney Injury - chemically induced; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Animals; aristolochic acid I; Aristolochic Acids; Body Weight - drug effects; Cholestenones - isolation & purification; Cholestenones - pharmacology; early renal injury; ergosta-4; ergosta‐4,6,8,22‐tetraen‐3‐one; Fibrosis; Kidney - pathology; Kidney Function Tests; Male; Nephritis, Interstitial - chemically induced; Nephritis, Interstitial - pathology; Polyporus - chemistry; Proteinuria - chemically induced; Proteinuria - pathology; Proteinuria - urine; Rats; Rats, Sprague-Dawley; renal interstitial fibrosis
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01361.x

Objectives  Aristolochic acid (AA) nephropathy, first reported as Chinese herbs nephropathy, is a rapidly progressive tubulointerstitial nephropathy that results in severe anemia, interstitial fibrosis and end‐stage renal disease. Tubulointerstitial injury was studied in a rat model of AA nephropathy to determine whether ergosta‐4,6,8(14),22‐tetraen‐3‐one (ergone) treatment prevents early renal injury in rats with aristolochic acid I‐induced nephropathy. Methods  Early renal injury via renal interstitial fibrosis was induced in rats by administration of aristolochic acid I (AAI) solution intragastrically for 8 weeks. Ninety‐six rats were randomly divided into four groups (n = 24/group): (1) control (2) AAI (3) AAI + ergone (10 mg/kg) and (4) AAI + ergone (20 mg/kg). Blood and urine samples were collected and rat were sacrificed for histological assessment of the kidneys on at the end of weeks 2, 4, 6 and 8. Key findings  AAI caused progressive elevation of blood urea nitrogen, creatinine, potassium, sodium, chlorine, proteinuria and urinary N‐acetyl‐β‐D‐glucosaminidase (NAG). Ergone suppressed elevation of blood urea, nitrogen, creatinine, proteinuria and urinary NAG to some degree, but the AAI–ergone‐treated group did not differ from AAI‐treated group for body weight, serum potassium, sodium and chlorine. The progress of the lesions in the kidney after AAI administration was also observed by histopathological examinations, but kidneys from rats of AAI–ergone‐treated group displayed fewer lesions. Conclusions  Ergone treatment conferred protection against early renal injury in a rat model of AA nephropathy. Early administration of ergone may prevent the progression of renal injury and the subsequent renal fibrosis in AA nephropathy.