Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents

AbstractParkinson ’s disease (PD) is a neurodegenerative disease that is accompanied with the loss of dopaminergic neurons in the substantia nigra pars compacta which subsequently leads to a reduction in the dopamine level in the striatum. The flavonoids are gaining critical attention in the management of PD due to the toxic effects of the synthetic drugs. Naringin, a potent flavonoid, exerts neuroprotective activity against experimental animal models of PD. It also exhibits protective activity against rotenone-induced neurotoxicity in cell line studies. Therefore, the present study was designed to evaluate t he therapeutic potential of naringin against rotenone-induced animal model of PD. The rotenone was injected through intracerebroventricular route into substantia nigra pars compacta (SNpc) to induce PD-like manifestations in the male rats. The behavioral deficits of the animals due to dopaminergic t oxicity were evaluated in actophotometer, OFT, bar catalepsy, narrow beam walk, rota-rod, grip strength and foot print analysis. Naringin-attenuated rotenone-induced behavioral abnormalities in the experimental rats. Further, naringin reduced the rotenone-induced dopaminergic toxicity in striatum an d SNpc the animals. At the sub-cellular level, naringin attenuated the rotenone-induced decrease in the mitochondrial function, integrity and bioenergetics in the SNpc of the animals. Furthermore, naringin reduced the rotenone-induced mitochondria-dependent apoptosis in the ...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research

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Authors: Ghazali R, Mehta KJ, Bligh SA, Tewfik I, Clemens D, Patel VB Abstract BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to reactive oxygen species (ROS)-mediated damage, perhaps leading to mitochondrial dysfunction. Therefore, these parameters were investigated to understand their contribution to N...
Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
This study showed that diet-induced hepatosteatosis, hyperlipidemia, and insulin resistance can be completely prevented in mice with liver-specific HCLS1-associated protein X-1 (HAX-1) inactivation. Mechanistically, we showed that HAX-1 interacts with inositol 1,4,5-trisphosphate receptor-1 (InsP3R1) in the liver, and its absence reduces InsP3R1 levels, thereby improving endoplasmic reticulum–mitochondria calcium homeostasis to prevent excess calcium overload and mitochondrial dysfunction. As a result, HAX-1 ablation activates pyruvate dehydrogenase and increases mitochondria utilization of glucose and fatty acids to...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Metabolism Source Type: research
ConclusionThe metal ions imbalance induces A β and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be p otential in ameliorating AD pathologies, which provides new research directions for AD treatment.
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
ConclusionsIn this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson ’s Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells’ secretome under oxidative stress; ii) the combined used of stat istical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an u...
Source: Translational Neurodegeneration - Category: Neurology Source Type: research
Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca2+). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that adaptive activation of mitochondrial dehydrogenases by intramitochondrial Ca2+ cannot be the exclusive mechanism for OXPHOS con...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Editors ' Picks Source Type: research
Authors: Khosravi S, Harner ME Abstract Mitochondria perform a plethora of functions in various cells of different tissues. Their architecture differs remarkably, for instance in neurons versus steroidogenic cells. Furthermore, aberrant mitochondrial architecture results in mitochondrial dysfunction. This indicates strongly that mitochondrial architecture and function are intimately linked. Therefore, a deep knowledge about the determinants of mitochondrial architecture and their function on a molecular level is of utmost importance. In the past decades, various proteins and protein complexes essential for formatio...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
In conclusion, intravenous neuronal mitochondria-targeted dual-modified novel biomimetic nanosystems are a promising therapeutic candidate for ROS-induced mitochondrial dysfunction in AD. PMID: 32228100 [PubMed - in process]
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
Mutations in the gene encoding the mitochondrial carrier protein SLC25A46 are known to cause optic atrophy associated with peripheral neuropathy and congenital pontocerebellar hypoplasia.We found novel biallelic SLC25A46 mutations (p.H137R, p.A401Sfs*17) in a patient with Parkinson's disease and optic atrophy. Screening of six unrelated patients with parkinsonism and optic atrophy allowed us to identify two additional mutations (p.A176V, p.K256R) in a second patient. All identified variants are predicted likely pathogenic and affect very conserved protein residues.
Source: Parkinsonism and Related Disorders - Category: Neurology Authors: Tags: Short communication Source Type: research
Purpose of review Despite improvements in acute kidney injury (AKI) detection, therapeutic options to halt the progression of AKI to chronic kidney disease (CKD) remain limited. In this review, we focus on recent discoveries related to the pathophysiology of the AKI to CKD continuum, particularly involving the renal tubular epithelial cells, and also discuss related ongoing clinical trials. While our focus is on injured renal tubular epithelial cells as initiators of the cascade of events resulting in paracrine effects on other cells of the kidney, the summation of maladaptive responses from various kidney cell types ult...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: RENAL IMMUNOLOGY AND PATHOLOGY: Edited by Agnes B. Fogo Source Type: research
AbstractAtherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanop...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: REVIEW Source Type: research
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