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Valproic acid and Piracetam treated liver showing restoration of PAS positive glycogen granules (Brown arrow). PASx400
Source publication
Valproic acid is one of the main antiepileptic drug which is a branched chain carboxylic acid used for absence seizures. The depletion of ß-oxidation as well as increased synthesis of toxic unsaturated valproic acid derivatives results in severe hepatotoxicity. Piracetam is a nootropic or cognitive enhancing agent which is used to treat cognitive i...
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Background
The liver was identified as a primary target organ for the chemo-radiological effects of uranyl acetate (UA). Although the anti-oxidant and anti-apoptotic properties of gallic acid (GA) make it a promising phytochemical to resist its hazards, there is no available data in this area of research.
Methods
To address this issue, eighteen ra...
Citations
Valproic acid is an antiepileptic drug. It acts by elevating GABA level in the CNS. It exerts therapeutic effects in a broad range of seizure (tonic-clonic, myoclonic, absence, partial) and bipolar disorder. The present work was carried out in the Department of Anatomy, IMS, BHU, Varanasi to evaluate the cytotoxic effect of valproate on fetal mice liver. Pregnant mice were exposed to single dose (8th gestational day) of Sodium valproate (200 mg/kg dose) intraperitoneally and fetuses were collected on 18th gestational day. The liver was smaller in size in valproate treated groups. Histologically, liver showed dilated central vein, breakage of endothelial lining of central vein, oedema and loss of normal architecture of liver parenchyma. Valproate was found teratogenic at 200 mg/kg dose in mice fetus. INTRODUCTION-Teratology is the science that studies the causes, mechanisms and patterns of abnormal development. The term teratology has been derived from the Greek word 'Teras' meaning 'monster' and 'Logos' meaning 'the study of '. The word monster is derived from Latin word 'monsterum' which means something providing for knowledge of coming events. Geottroy Saint Hilaire coined the term 'Teratology' (studying serious deviations from the normal type) to designate the science of monsters.
Background
Chronic psychological distress is considered today a pandemic due to the modern lifestyle and has been associated with various neurodegenerative, autoimmune, or systemic inflammation-related diseases. Stress is closely related to liver disease exacerbation through the high activity of the endocrine and autonomic nervous systems, and the connection between the development of these pathologies and the physiological effects induced by oxidative stress is not yet completely understood. The use of nootropics, as the cognitive enhancer and antioxidant piracetam, is attractive to repair the oxidative damage. A proteomic approach provides the possibility to obtain an in-depth comprehension of the affected cellular processes and the possible consequences for the body. Therefore, we considered to describe the effect of distress and piracetam on the liver proteome.
Methods
We used a murine model of psychological stress by predatory odor as a distress paradigm. Female Sprague-Dawley rats were distributed into four experimental groups ( n = 6 − 7/group) and were exposed or not to the stressor for five days and treated or not with piracetam (600 mg/kg) for six days. We evaluated the liver proteome by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-SDS-PAGE) followed by liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Besides, we analyzed the activity of liver antioxidant enzymes, the biochemical parameters in plasma and rat behavior.
Results
Our results showed that distress altered a wide range of proteins involved in amino acids metabolism, glucose, and fatty acid mobilization and degradation on the way to produce energy, protein folding, trafficking and degradation, redox metabolism, and its implications in the development of the non-alcoholic fatty liver disease (NAFLD). Piracetam reverted the changes in metabolism caused by distress exposure, and, under physiological conditions, it increased catabolism rate directed towards energy production. These results confirm the possible relationship between chronic psychological stress and the progression of NAFLD, as well as we newly evidenced the controversial beneficial effects of piracetam. Finally, we propose new distress biomarkers in the liver as the protein DJ-1 (PARK7), glutathione peroxidase 1 (GPX), peroxiredoxin-5 (PRDX5), glutaredoxin 5 (GLRX5), and thioredoxin reductase 1 (TXNDR1), and in plasma as biochemical parameters related to kidney function such as urea and blood urea nitrogen (BUN) levels.
