Increased Cortical Neuronal Survival During Liver Injury: Effect of Gamma Aminobutyric Acid and 5-HT Chitosan Nanoparticles

Abstract

Use of nanoparticulate drug delivery system for an effective therapeutic outcome against diseases gains immense hope in the study of drug delivery to partially hepatectomised rats. In the present study, partially hepatectomised rats treated with Gamma aminobutyric acid (GABA) and serotonin (5-HT) chitosan nanoparticles, individually and in combination, were evaluated to analyse their role in GABAB, and 5-HT2A receptors functional regulation, interrelated neuronal survival mechanisms by nuclear factor kappa B (NF-kappaB), tumour necrosis factor-a (TNF-alpha), Akt-1 and the antioxidant enzyme superoxide dismutase (SOD) in the cerebral cortex. A significant decrease in GABA, and 5-HT2A receptor numbers and gene expressions denoted a homeostatic adjustment by the cerebral cortex to trigger the sympathetic innervations during elevated DNA synthesis in the liver. GABAB, and 5-HT2A signalling directly influenced the cyclic AMP response element binding protein (CREB) expression, neuronal survival and ROS mediated cell damage which was confirmed from the gene expression of NF-kappaB, TNF-alpha, Akt-1 and SOD. In addition to enhanced hepatocyte proliferation, GABA and 5-HT chitosan nanoparticle treatment protected the neurons from ROS mediated cell damage and promoted their survival in the cerebral cortex. This has application in liver based diseases and treatments with nanosized active compounds.

<p>Long Noncoding RNA H19 Induces Neuropathic Pain by Upregulating Cyclin-Dependent Kinase 5-Mediated Phosphorylation of cAMP Response Element Binding Protein</p>

“… 38 Furthermore, in rats with liver injury, 5-HT 2A and GABA B2 directly repressed CREB expression, exerting protective effects on liver neurons. 39 Increased CREB phosphorylation in the dorsal horn resulted in an increase in histone H4 acetylation in the CDK5 promoter and upregulated CDK5 transcription, so suppressed CREB expression reduced CDK5 growth and relieved rat mechanical allodynia. 13 Importantly, it was previously indicated that dysregulated H19 can directly or indirectly modulate many different carcinogenic factors, including CDK.…”

Parboiled Germinated Brown Rice Decreases Inflammatory Cytokines Levels in Various Regions of Brain in Rats Induced by Carbon Tetrachloride

“…A previous study by Hou (2011) reported that GABA prevented kainic acid (KA)-induced neuronal injury by suppressing lipid peroxidation in male FVB mice brains and inhibiting ROS accumulation in the rat's pheochromocytoma cell line (PC12). Moreover, Shilpa et al (2014) revealed that treatment of GABA and serotonin (5-HT) chitosan nanoparticles in partially hepatectomised rats were able to protect the neurons from ROS mediated cell damage and promoted their survival in the cerebral cortex by means of the regulation of the gene expression of NF-B, TNF-α, and superoxide dismutase (SOD). Therefore, the several bioactive compounds found in PGBR may suppress CCl 4 -induced liver and brain oxidative damage contributing to the inhibition of brain inflammation.…”