@conference{
author = "Šošić-Jurjević, Branka and Jovanović, Ljubiša and Marina, Ljiljana and Ristić, Nataša and Miler, Marko and Ajdžanović, Vladimir and Filipović, Branko and Luetjohann, Dieter",
year = "2022",
abstract = "The cholesterol oxidation product 27-hydroxycholesterol (27OHC) is enzymatically
produced from cholesterol by CYP27A1 in an alternative pathway of
cholesterol degradation to bile acids. This oxysterol also acts as an endogenous
selective estrogen receptor modulator (SERM). In healthy humans its
concentration in circulation increases in hypercholesterolemia and with age,
and is associated with increased risk of atherosclerosis, cardiovascular diseases
and breast cancer. Several drugs with SERM activity used for treatments of breast
cancer or osteoporosis have been reported to have sporadic hepatotoxic effects.
Women suffer from some liver diseases more commonly (acute liver failure,
autoimmune hepatitis, benign liver lesions, or primary biliary cirrhosis). For all of
these the incidence increases with advancing age. To the best of our knowledge,
there is no information in the literature, clinical or experimental, relating changes
in hepatic 27OHC with incidence of liver disease in the context of aging and sex.
To address this problem, we examined the effect of age and sex on liver and serum
concentrations of 27OHC, as well as the immunostaining pattern of CYP27A1 in
the liver of four-month and 24-month-old Wistar rats (experiments were repeated
twice with similar results, nZ5-6 animals/group) using LC MS/MS and
immunohistochemistry, respectively. Furthermore, we examined changes in
total cholesterol and concentration in liver and serum, liver histopathology, as
well as serum concentration of hepatic enzymes, alanine (ALT) and aspartate
aminotransferase (AST). The effect of age (P!0.05) on increase of serum and
hepatic 27OHC was obtained both in males and females (P!0.05) and followed
the same pattern of age-related total cholesterol increase (P!0.05). However, the
intrahepatic increase of 27OHC was dramatically more pronounced only in oldaged
females (P!0.0001). CYP27A1 immunostaining intensity was similar in all
experimental groups, being the strongest in the cytoplasm of centrilobular
hepatocytes, but the immunopositivity was diffusely spread throughout the liver
lobule. Histopathological analysis revealed age-related hepatocellular degeneration
(swelling and hydropic degeneration, increased fraction of binuclear
hepatocytes and focal fatty changes) only in females. Moreover, age-related
elevation of alanine transaminase (ALT) was observed only in female rats (P!
0.01). In conclusion, the obtained results confirmed age-related female-specific
increase of hepatic 27OHC as well as hepatocyte degeneration obsereved only in
the liver of rat females. These age-related adaptive changes in cholesterol
metabolism may atenuate hepatoprotective estrogen-like effects in the liver.",
publisher = "bioscientifica",
journal = "24th European Congress of Endocrinology 2022; 21–24 May 2022; Milan, Italy",
title = "Is age-related hepatic elevation of endogenous SERM 27-hydroxycho lesterol associated with hepatocellular degeneration female-specific? - Results from Rat study?",
doi = "10.1530/endoabs.81.P615",
pages = "P615"
}
