Monocrotaline (MCT) is a pyrrolizidine alkaloid present in plants of the Crotalaria species that causes cytotoxicity and genotoxicity, including hepatotoxicity in animals and humans. It is metabolized by cytochrome P-450 in the liver to the alkylating agent dehydromonocrotaline (DHM). In previous studies using isolated rat liver mitochondria, we observed that DHM, but not MCT, inhibited the activity of respiratory chain complex I and stimulated the mitochondrial permeability transition with the consequent release of cytochrome c. In this study, we evaluated the effects of MCT and DHM on isolated rat hepatocytes. DHM, but not MCT, caused inhibition of the NADH-linked mitochondrial respiration. When hepatocytes of rats pre-treated with dexamethasone were incubated with MCT (5 mM), they showed ALT leakage, impaired ATP production and decreased levels of intracellular reduced glutathione and protein thiols. In addition, MCT caused cellular death by apoptosis. The addition of fructose or dithiotreitol to the isolated rat hepatocyte suspension containing MCT prevented the ATP depletion and/or glutathione or thiol oxidation and decreased the ALT leakage and apoptosis. These results suggest that the toxic effect of MCT on hepatocytes may be caused by metabolite-induced mitochondrial energetic impairment, together with a decrease of cellular glutathione and protein thiols.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.toxicon.2011.04.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Extracellular Matrix Alterations Due to Early-Life Adversity: Implications for Auditory Learning in Male Sprague-Dawley Rats.
Mol Neurobiol
January 2025
Department of Physiology, Hamidiye Faculty of Medicine, University of Health Sciences, Istanbul, Turkey.
This study aimed to investigate the impact of early childhood chronic stress on the development of the brain extracellular matrix (ECM) and how alterations in the ECM following early-life adversity (ELA) affect auditory learning and cognitive flexibility. ELA was induced through a combination of maternal separation and neonatal isolation in male Sprague-Dawley rats, and the success of the ELA model was assessed behaviorally and biochemically. A cortex-dependent go/no-go task with two phases was used to determine the impact of ELA on auditory learning and cognitive flexibility.
View Article and Find Full Text PDFComplete genome sequence of GL-4.
Microbiol Resour Announc
January 2025
Guangxi Key Laboratory of Veterinary Biotechnology, Key Laboratory of China (Guangxi)-ASEAN Cross-border Animal Disease Prevention and Control, Ministry of Agriculture and Rural Affairs of China, Guangxi Veterinary Research Institute, Nanning, China.
A cellulase-producing was previously isolated from the intestinal tract of domestic bamboo rat and identified as GL-4. In this study, we present the complete genome sequence of GL-4. The genome is 4,271,214 bp long, with a guanine-cytosine content of 43.
View Article and Find Full Text PDFEngineering Highly Aligned and Densely Populated Cardiac Muscle Bundles via Fibrin Remodeling in 3D-Printed Anisotropic Microfibrous Lattices.
Adv Mater
January 2025
State Key Laboratory for Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.
Replicating the structural and functional features of native myocardium, particularly its high-density cellular alignment and efficient electrical connectivity, is essential for engineering functional cardiac tissues. Here, novel electrohydrodynamically printed InterPore microfibrous lattices with anisotropic architectures are introduced to promote high-density cellular alignment and enhanced tissue interconnectivity. The interconnected pores in the microfibrous lattice enable dynamic, cell-mediated remodeling of fibrous hydrogels, resulting in continuous, mechanically stable tissue bundles.
View Article and Find Full Text PDFThe effect of platelet-rich plasma on ferroptosis of nucleus pulposus cells induced by Erastin.
Biochem Biophys Rep
March 2025
Orthopedics of TCM Senior Department, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, China.
Background: Intervertebral disc degeneration (IVDD) has been linked to ferroptosis, a type of programmed cell death. The role of platelet-rich plasma (PRP) in mitigating ferroptosis in nucleus pulposus (NP) cells within IVDD remains unclear.
Purpose: This study aims to verify the effectiveness of PRP in reducing ferroptosis in NP cells induced by Erastin.
Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.
J Physiol
January 2025
Department of Nutrition and Exercise Physiology, University of Missouri-Columbia, Columbia, Missouri, USA.
Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!