Subject(s)
Anti-Inflammatory Agents/administration & dosage , Antiviral Agents/administration & dosage , COVID-19 Drug Treatment , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/virology , Drug Repositioning , Drug Therapy, Combination , Humans , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Mitochondrial dysfunction is involved in neurodegenerative diseases, such as Huntington's disease (HD). 3-Nitropropionic acid (3-NP) is a mitochondrial toxin that specifically inhibits complex II of the electron transport chain (ETC) and is used to generate an experimental model of HD. OBJECTIVE: To study the effect of fish liver oil (FO) over the mitochondrial dysfunction induced via partial ETC inhibition by 3-NP. METHODS: This study was performed in rats and consisted of two phases: (i) administration of increasing doses of 3-NP and (ii) administration of FO for 14 days before to 3-NP. The rats' exploratory activity; complex I, II, III, and IV activities; and rearing behavior were observed. Additionally, the number of TUNEL-positive cells and various mitochondrial parameters, including oxygen consumption, transmembrane potential, adenosine triphosphate synthesis, and ETC activity, were measured. RESULTS: We observed that FO exerted a protective effect against the 3-NP-induced toxicity, although complex II inhibition still occurred. Instead, this effect was related to strengthened mitochondrial complex III and IV activities. DISCUSSION: Our results show that FO exerts a beneficial prophylactic effect against mitochondrial damage. Elucidating the mechanisms linking the effects of FO with its prevention of neurodegeneration could be the key to developing recommendations for FO consumption in neurological pathologies.
Subject(s)
Corpus Striatum/drug effects , Fish Oils/pharmacology , Mitochondria/drug effects , Animals , Antioxidants , Cytochrome-c Peroxidase/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Electron Transport Complex II/antagonists & inhibitors , Electron Transport Complex II/metabolism , Electron Transport Complex IV/metabolism , Huntington Disease/chemically induced , Huntington Disease/drug therapy , In Situ Nick-End Labeling , Lipid Peroxidation , Male , NAD/metabolism , Neuroprotective Agents/pharmacology , Nitro Compounds , Oxidative Stress/drug effects , Propionates , Rats , Rats, WistarABSTRACT
Research on the postnatal development of pancreatic beta-cells has become an important subject in recent years. Understanding the mechanisms that govern beta-cell postnatal maturation could bring new opportunities to therapeutic approaches for diabetes. The weaning period consists of a critical postnatal window for structural and physiologic maturation of rat beta-cells. To investigate transcriptome changes involved in the maturation of beta-cells neighboring this period, we performed microarray analysis in fluorescence-activated cell-sorted (FACS) beta-cell-enriched populations. Our results showed a variety of gene sets including those involved in the integration of metabolism, modulation of electrical activity, and regulation of the cell cycle that play important roles in the maturation process. These observations were validated using reverse hemolytic plaque assay, electrophysiological recordings, and flow cytometry analysis. Moreover, we suggest some unexplored pathways such as sphingolipid metabolism, insulin-vesicle trafficking, regulation of transcription/transduction by miRNA-30, trafficking proteins, and cell cycle proteins that could play important roles in the process mentioned above for further investigation.
