Role of Caspase-12 in Hepatocyte Apoptosis Induced by Carbon Tetrachloride in Mice | Chapter 13 | Medical Science: Trends and Innovations Vol. 10

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

Research on Liver Organoid: Present Situation, Limiting Factors and Future Therapeutical Potential in Pediatric Diseases | Chapter 9 | Advancement and New Understanding in Medical Science Vol. 10

 Scientists often use organoids to research diseases. Organoids are three-dimensional, organ-like cell assemblies in which different cell types have organized themselves in a way that is approximately typical for the corresponding organ in the body. They show three characteristics: self-organization, multicellularity and functionality. This study concentrates on liver organoid research and its future role in different pediatric diseases. The range of organs that can be studied with organoids is growing rapidly and includes the brain, intestine, kidney, stomach, pancreas, lung, liver, prostate, esophagus, gallbladder, and the female reproductive tract, among others, and also the embryo. Organoids enable the scientific study of human development, physiology and pathology on a scale. Organoids are grown either from pluripotent stem cells or from tissue-specific adult stem cells. Adult stem cells are present in a large number of tissues and are responsible for renewing the cells in these tissues. They can only give rise to the cell types that are present in the particular tissue, the stem cell of the intestinal epithelium only produces cells of the intestinal epithelium, but not muscle cells or nerve cells. They are thus multipotent. Today, it is possible to reconstruct organ-like tissue organoids in the laboratory. Stem cells are thereby induced to differentiate by molecular signals and grown in culture systems that promote their three-dimensional self-organization. Rapidly developing organoid technology makes it possible to phenotypically copy cell structure. To some extent, this is also true for the functions of various human organs (for example, brain, thyroid, thymus, intestine, liver, pancreas, stomach, lung, kidney) and even early-stage embryos. As near-physiological 3D culture systems, organoids open up new possibilities to study the development of healthy and diseased organs and offer great potential for translational research. Further research in the field of paediatrics will show further development of in vivo use of organoids in the future, especially in liver diseases in childhood.

Author(s) Details:

Stefan Bittmann,
Department of Pediatrics, Ped Mind Institute, Medical and Finance Center Epe, Hindenburgring 4, 48599 Gronau, Germany.

Gloria Villalon,
Department of Pediatrics, Ped Mind Institute, Medical and Finance Center Epe, Hindenburgring 4, 48599 Gronau, Germany.

Elena Moschüring-Alieva,
Department of Pediatrics, Ped Mind Institute, Medical and Finance Center Epe, Hindenburgring 4, 48599 Gronau, Germany.

Lara BIttmann,
Department of Pediatrics, Ped Mind Institute, Medical and Finance Center Epe, Hindenburgring 4, 48599 Gronau, Germany.

Elisabeth Luchter,
Department of Pediatrics, Ped Mind Institute, Medical and Finance Center Epe, Hindenburgring 4, 48599 Gronau, Germany.

Please see the link here: https://stm.bookpi.org/ANUMS-V10/article/view/13957