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aThe Second Department of Cardiovascular Medicine, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
bInternal Medicine Department, Gannan County People’s Hospital, Qiqihar, China
cCollege of Pharmacy, Qiqihar Medical University, Qiqihar, China
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Article / Publication DetailsFirst-Page Preview
Received: March 11, 2022
Accepted: September 14, 2022
Published online: November 24, 2022
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
AbstractIntroduction: Atorvastatin (ATO) is often used to reduce blood lipids and prevent atherosclerosis, but excessive use of ATO will lead to hepatotoxicity. This paper investigated the effects of astragaloside IV (AS IV), which has multiple biological functions, on ATO-induced hepatotoxicity and the underlying mechanism. Methods: ATO treatment induced a rat model of hepatotoxicity, followed by AS IV treatment. Colorimetric kits were used to detect rat liver function indexes including aspartate aminotransferase (AST), alanine transaminase (ALT), malondialdehyde (MDA), and reduced glutathione (GSH). Reactive oxygen species (ROS) level was determined by 2′, 7′-Dichlorodihydrofluorescein diacetate kit. The liver fibrosis and F4/80 expression were detected by Sirius red staining and immunochemistry. Mitochondrial electron transport chain complex I and complex IV activities were examined. The level of mitochondrial membrane potential (MMP) was detected by JC-1 staining. The inflammatory factor levels were detected by quantitative real-time polymerase chain reaction. Western blot detected apoptosis-related proteins and AMPK/SIRT1-related proteins. Results: ATO increased ALT, AST, MDA, and ROS levels and decreased GSH content but was subsequently reversed by AS IV. AS IV alleviated liver tissue damage caused by ATO. AS IV elevated complex I and complex IV activity and promoted MMP levels in ATO rats. ATO promoted inflammatory factor release in SD rats but was then suppressed by AS IV. AS IV inhibited Bax, cleaved caspase-3 but up-regulated Bcl-2 in ATO-induced rats. ATO inhibited SIRT1 expression and AMPK phosphorylation, which was subsequently promoted by AS IV. Conclusion: AS IV inhibits ATO-induced hepatotoxicity by activating the AMPK/SIRT1 pathway.
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Received: March 11, 2022
Accepted: September 14, 2022
Published online: November 24, 2022
Number of Print Pages: 9
Number of Figures: 3
Number of Tables: 0
ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)
For additional information: https://www.karger.com/PHA
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