Biocharacterization of Heat Shock Protein 90 in Acetaminophen-Treated Livers Without Conspicuous Drug Induced Liver Injury

Abstract

Background/Aims: Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms. Heat shock protein 90 (Hsp90) is to be expressed during various stresses, such as wound healing and tissue remodeling. Recently, it is discovered that Hsp90 is a potential modifier of cytogenesis. In comparison to clinical references of liver damage, this study was designed to assess the potential bioeffect of Hsp90 in APAP-treated livers without conspicuous drug induced liver injury (DILI). Methods: In our current study, human plasma samples of APAP-used patients were collected for biochemical assays in clinical parameters. Adult male mice were used to investigate the biocharacterization of Hsp90 in APAP-treated livers through serological tests and immunoassays. Further, a mouse liver cell strain was employed in assessment of bioeffect of APAP on hepatocellular Hsp90 expression. Results: Correspondingly, the clinical data showed APAP-administered patients resulted in increased Hsp90 levels in serum when compared to other clinical parameters of liver injury. In adult mice study, APAP-treated livers showed unchanged hepatocellular and metabolic functions, as highlighted in biochemical analysis and immunoassay. Notably, Hsp90 expression in APAP-treated mice were elevated in the serum and liver samples. In quantitative western blot assay, the present data suggested that hepatocellular Hsp90 level was up-regulated followed by APAP treatment. In mouse cell strain study, APAP-treated liver cells had increased trend of aminotransferase contents and apoptotic counts. Further, endogenous Hsp90 expression in APAP-exposed cells was increased dose- and time-dependently. Conclusions: In conclusion, our current findings disclose that Hsp90 biomolecule may be a potential indicator for APAP-induced inconspicuous DILI, in which it seems to be characterized with more sensitive than other diagnosis criteria.

Pterostilbene Reduces Acetaminophen-Induced Liver Injury by Activating the Nrf2 Antioxidative Defense System via the AMPK/Akt/GSK3β Pathway

“…Drug-induced liver injury (DILI) has been reported to be one of the main reasons for the withdrawal of many clinically used drugs and the most common cause of acute liver failure [1], which represents a major challenge in designing potential therapies [2]. Acetaminophen (APAP), a widely used analgesic and antipyretic drug worldwide, has been reported to be the main reason for DILI in the United States and the United Kingdom [3,4].…”

Antihepatotoxic benefits of Poria cocos polysaccharides on acetaminophen‐lesioned livers in vivo and in vitro

“…Cleaved PARP are required for cellular functions, such as production of inflammatory genes, and in response to TNF cytokines . Hsp90 is a molecular chaperone that induces other molecules to fold properly, and to stabilize proteins for blocking heat stress, and it modulates a number of proteins necessary for cell growth . Therefore, we reasoned that Hsp90 biomolecule may activate in response to APAP‐induced hepatocellular stresses.…”

Potential biomarker of fibroblast growth factor 21 in valproic acid‐treated livers

“…The sections were developed with hydrogen peroxidase enzyme‐labeled diaminobenzidine dye. Subsequently, all sections were redyed with hematoxylin in nucleoli …”