Fenofibrate impairs liver function and structure more pronounced in old than young rats

• Published in: Archives of gerontology and geriatrics 2020-11, Vol.91, p.104244-104244, Article 104244
• Main Authors: Zubrzycki, Adrian, Wrońska, Agata, Kotulak-Chrząszcz, Anna, Wierzbicki, Piotr Mieczysław, Kmieć, Zbigniew
• Format: Article
• Language: English
• Subjects: Aging; Fenofibrate; Lipids; Liver function and morphology; Rat; serum
• ISSN: 0167-4943; 1872-6976
• DOI: 10.1016/j.archger.2020.104244

•FN at a higher dose (0.5 %) decreases body mass in both young and old rats.•FN induces more prominent hypolipemic effect in old than in young animals.•0.5 % FN increases serum alkaline phosphatase activity in young and old rats.•In old rats, higher FN dose moderately increases the activity of ALT, whereas in young animals neiher dose of FN affects the activities of aminotransferases.•FN impairs liver morphology in old as well as young rats. Since old animals are known to accumulate lipids in some organs, we compared effects of fenofibrate (FN) on systemic lipid metabolism, activity of liver marker enzymes and structure in young and old rats. Young and old rats were fed chow supplemented with 0.1 % or 0.5 % FN. After 30 days, intraperitoneal glucose tolerance test (IPGTT) was performed, and blood and liver samples were collected. In young rats, 0.1 % FN, but not 0.5 % FN, decreased serum Chol by 74 %, and did not affect TG levels at either doses. In old rats, 0.5 % FN, but not 0.1 % FN, decreased Chol and TG level by 56 % and 49 %, respectively. In young rats, 0.1 % and 0.5 % FN increased serum activity of ALP by 227 % and 260 %, respectively, and did not affect AST and ALT activities. In old rats, only 0.5 % FN increased serum ALP activity by 150 %, respectively. In old rats, neither dose of FN affected serum AST activity, and only 0.5 % FN increased serum ALT activity by 200 %. The histological examination of liver structure revealed that both doses of FN impaired lobular architecture, expansion of bile canaliculi, and degeneration of parenchymal cells with the presence of cells containing fat droplets; administration of FN increased area occupied by collagen fibers. Although 0.5 % FN decreased serum Chol concentration, it increased serum ALP activity and impaired liver structure in both in both age groups of rats. Thus, FN treatment should be under the control of liver function, especially in older patients.