Characterization of acetaminophen-induced cytotoxicity in target tissues.
Acetaminophen (APAP), commonly used in clinical prescription, has time- and dose-dependent side effects. Thus, further animal study warrants to be investigated to assess possible adverse effect of APAP application. Here, we conducted pre-clinical research to elucidate the molecular mechanism regarding APAP-mediated toxicological action. Our data showed that serous/urinary and hepatic/renal APAP concentrations were significantly increased when compared with normal control, which the liver tissue showed the highest level. As an acute liver damage model induced by APAP, absolute liver weight, serum enzyme (ALT), urine protein content were notably elevated. Representatively, APAP-damaged liver resulted in increased pro-apoptotic Bax and compensatory Ki-67 positive cells, while the number of anti-apoptotic Bcl2 positive cells was reduced. In addition, the immunoactivity markers for NF-κB, TRL4, TNF-α in the kidney were increased, respectively. Furthermore, intracellular TRL4 and TNF-α mRNAs in the liver and kidney showed significant up-regulation. In summary, our current findings demonstrate that APAP-mediated the specific cytotoxicity is linked to the molecular mechanisms of facilitating apoptosis and inflammatory stress in the liver and kidney.
Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
Chao
C
Guo
Department of Gynecology, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
Guojie
G
Xie
Guilin Medical University Guilin 541004, Guangxi, PR China.
Min
M
Su
Guangxi Medical University Guilin 541004, Guangxi, PR China.
Xinmou
X
Wu
Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
Xiuli
X
Lu
Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University Guangxi, Nanning 530031, PR China.
Ka
K
Wu
Department of Pharmacy, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University Guigang 537100, Guangxi, PR China.
Chaohe
C
Wei
Acetaminophen; cytotoxicity; kidney; liver