Toxic liver damage can lead to acute liver failure, hepatic fibrosis, and even carcinogenesis. This study aimed to explore the role of caspase-12 and its downstream targets in hepatocyte apoptosis induced by carbon tetrachloride (CCl4). To determine the role of caspase-12, caspase-12 knockout mice were used. Wild-type and caspase-12 knockout mice received a single intraperitoneal injection of either CCl4 (300 μl/kg BW) or vehicle (corn oil). The animals were sacrificed 24 hours after treatment, and blood samples were collected to assess liver function through alanine aminotransferase activity. Liver samples were analyzed for reactive oxygen species (ROS) levels using plasma malondialdehyde as a biomarker, hepatocyte apoptosis via TUNEL assay and morphological analysis, and cytochrome C release and caspase activation through western blotting.
In wild-type mice, low-dose CCl4 administration caused
hepatocyte apoptosis and acute liver injury, accompanied by increased ROS
production and endoplasmic reticulum (ER) stress in the liver. These events
triggered the activation of caspases-12, -9, and -3, along with the release of
small amounts of cytochrome C. However, in CCl4-treated caspase-12
knockout mice, the activation of caspases-9 and -3 was significantly reduced,
while cytochrome C release remained unaffected. Compared to wild-type mice, CCl4-induced
apoptosis and liver damage were substantially attenuated in caspase-12 knockout
mice (p < 0.05). Notably, the active form of caspase-8 was not detected in
either wild-type or knockout mice. Additionally, there was no significant
difference in ROS formation between the two groups following CCl4 treatment.
These findings demonstrate that caspase-12 plays a critical role
in CCl4-induced hepatic apoptosis by directly or indirectly
activating effector caspase-3 downstream, with partial involvement of caspase-9
activation. In conclusion, prolonged exposure to even low levels of CCl4
could cause liver pathology in humans, warranting further clinical and animal
studies to investigate the long-term consequences of minimal exposure.
Author (s) Details
Hua Liu
Division of Pediatric Gastroenterology, Department of Pediatrics,
University of Mississippi Medical Center, 2500 North State Street, Jackson, MS
39216, USA.
Madison Nicole Burton
University of Mississippi Medical Center, Jackson, MS 39216, USA.
Neha Dhaliwal
William Carey University, 710 William Carey Pkwy, Hattiesburg, MS 39401,
USA.
Please see the book here:- https://doi.org/10.9734/bpi/msti/v10/4801
