title: Hepatotoxicity and nephrotoxicity produced by 4-hydroxy-2-nonenal (4-HNE) following 4-week oral administration to Sprague-Dawley rats.
abstract: 4-Hydroxy-2-nonenal (4-HNE) is a major end product of lipid peroxidation of membrane n-6 polyunsaturated fatty acids, which are found in food products. In order to examine the toxicity attributed to 4-HNE, a subacute toxicity study was conducted in Sprague-Dawley (SD) rats. For this study, 4 groups of 10 male and 10 female rats were administered by gavage either 0 (control), 0.5, 2.5, or 12.5 mg 4-HNE/kg body weight/d for 28 d, and then sacrificed for blood and tissue sampling. No significant changes in body weight or clinical signs were observed, but biochemical analysis showed significant alterations in hepatotoxicity biomarkers, such as levels of serum albumin and total bilirubin, and aspartate aminotransferase (AST) activity, and in nephrotoxicity biomarkers, such as levels of blood urea nitrogen (BUN) and creatinine and activity of alkaline phosphatase (ALP), and urinary creatinine and protein levels at 0.5 mg/kg/d. In addition, significant increases in kidney and brain weights and a significant decrease in small intestine weight were noted at 12.5 mg/kg/d. Histologic examinations of kidneys showed hyaline droplets or accumulation of hyaline bodies in renal tubules and degeneration of tubular epithelium cells. These results demonstrate that oral daily exposure to 4-HNE for 28 d produced hepatotoxicity and nephrotoxicity. The no-observed-adverse-effect level (NOAEL) for 4-HNE was calculated to be <0.5 mg 4-HNE/kg/d.
authors.affiliation: Department of Natural Product Resources, Semyung University, Jecheon, South Korea.
authors.forename: Se Chan
authors.initials: SC
authors.lastname: Kang
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Kyu Bong
authors.initials: KB
authors.lastname: Kim
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kwack
authors.forename: Il Young
authors.initials: IY
authors.lastname: Ahn
authors.forename: Jung Yun
authors.initials: JY
authors.lastname: Bae
authors.forename: Seoung Kwang
authors.initials: SK
authors.lastname: Lim
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000447:Aldehydes / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009393:Nephritis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000447:Aldehydes; D015415:Biomarkers; C027576:4-hydroxy-2-nonenal