6-Hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline Demonstrates Neuroprotective Properties in Experimental Parkinson's Disease by Enhancing the Antioxidant System, Normalising Chaperone Activity and Suppressing Apoptosis.

Parkinson's disease (PD) is a neurodegenerative disease, whereby disturbances within the antioxidant defence system, increased aggregation of proteins, and activation of neuronal apoptosis all have a crucial role in the pathogenesis. In this context, exploring the neuroprotective capabilities of compounds that sustain the effectiveness of cellular defence systems in neurodegenerative disorders is worthwhile. During this study, we assessed how 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ), which has antioxidant properties, affects the functioning of the antioxidant system, the activity of NADPH-generating enzymes and chaperones, and the level of apoptotic processes in rats with rotenone-induced PD.

Aging, Neurodegenerative Disorders, and Cerebellum.

An important part of the central nervous system (CNS), the cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results in the motor and cognitive impairment observed in patients with neurodegenerative disorders such as Alzheimer's disease (AD), vascular dementia (VD), Parkinson's disease (PD), Huntington's disease (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich's ataxia (FRDA), and multiple sclerosis (MS), and even during the normal aging process. In most neurodegenerative disorders, impairment mainly occurs as a result of morphological changes over time, although during the early stages of some disorders such as AD, the cerebellum also serves a compensatory function.

6-Hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline Demonstrates Anti-Inflammatory Properties and Reduces Oxidative Stress in Acetaminophen-Induced Liver Injury in Rats.

We examined the effects of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of liver injury, oxidative status, and the extent of inflammatory and apoptotic processes in rats with acetaminophen-induced liver damage. The administration of acetaminophen caused the accumulation of 8-hydroxy-2-deoxyguanosine and 8-isoprostane in the liver and serum, as well as an increase in biochemiluminescence indicators. Oxidative stress resulted in the activation of pro-inflammatory cytokine and NF-κB factor mRNA synthesis and increased levels of immunoglobulin G, along with higher activities of caspase-3, caspase-8, and caspase-9.

SkQ1 Improves Immune Status and Normalizes Activity of NADPH-Generating and Antioxidant Enzymes in Rats with Adjuvant-Induced Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a severe systemic autoimmune inflammatory disease. Oxidative stress and excessive formation of reactive oxygen species (ROS) by the mitochondria are considered as the central pathogenetic mechanisms of connective tissue destruction and factors responsible for a highly active inflammatory process and autoimmune response. The aim of this work was to evaluate the effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) on the immune status, intensity of free radical-induced oxidation, and functioning of the antioxidant system (AOS) and NADPH-generating enzymes in rats with the adjuvant-induced RA.

6-Hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline Alleviates Oxidative Stress and NF-κB-Mediated Inflammation in Rats with Experimental Parkinson's Disease.

A study was conducted to investigate the effects of different doses of 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ) on motor coordination scores, brain tissue morphology, the expression of tyrosine hydroxylase, the severity of oxidative stress parameters, the levels of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) factor, and the inflammatory response in rats during the development of rotenone-induced Parkinsonism. The findings indicate that HTHQ, with its antioxidant attributes, reduced the levels of 8-isoprostane, lipid oxidation products, and protein oxidation products. The decrease in oxidative stress due to HTHQ led to a reduction in the mRNA content of proinflammatory cytokines and myeloperoxidase activity, accompanying the drop in the expression of the factor NF-κB.

Indole-3-carbinol mitigates oxidative stress and inhibits inflammation in rat cerebral ischemia/reperfusion model.

Ischemia is a significant pathogenetic factor of stroke with very limited treatment options. The objective of our research was to evaluate the protective properties of indole-3-carbinol (I3C) and its effect on redox status parameters, inflammation, and apoptosis intensity in cerebral ischemia/reperfusion injury (CIRI) in rats. I3C administration to CIRI rats decreased levels of oxidative stress markers and improved aerobic metabolism compared to the animals with CIRI.

The new antioxidant 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline has a protective effect against carbon tetrachloride-induced hepatic injury in rats.

Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide. Therefore, dihydroquinoline derivatives, which are precursors of hepatoprotectors and have antioxidant activity, are of interest. We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.

1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline exerts a neuroprotective effect and normalises redox homeostasis in a rat model of cerebral ischemia/reperfusion.

Ischemia is one of the main etiological factors of stroke and is associated with the development of energy deficiency, oxidative stress, and inflammation. An abrupt restoration of blood flow, called reperfusion, can worsen the effects of ischemia. In our study, we assessed the neuroprotective potential of 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (BHDQ) in cerebral ischemia/reperfusion (CIR) in rats.

Inflammation is associated with impairment of oxidative status, carbohydrate and lipid metabolism in type 2 diabetes complicated by non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is accompanied by inflammation and impairment of the lipid metabolism. In addition, NAFLD is one of the major complications of type 2 diabetes associated with oxidative stress. Based on this, we evaluated the tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), oxidative status rates, and analyzed its correlation with carbohydrate and lipid metabolism in patients with NAFLD and type 2 diabetes.

Functioning of the Antioxidant Defense System in Rotenone-Induced Parkinson's Disease.

A comprehensive study of the functioning of antioxidant system in rats with rotenone-induced parkinsonism was conducted. The development of pathology led to inhibition of the majority of the studied antioxidant enzymes in the brain and blood serum of animals, which can be associated with decompensation of oxidative stress under conditions of prolonged mitochondrial dysfunction. These changes apparently make an important contribution into neuronal degeneration in the cerebral cortex and striatum and motor disorders in experimental animals.

The effect of methylethylpiridinol addition to the therapy on the level of pigment epithelium-derived factor and oxidative status in patients with diabetic nephropathy: randomized controlled open-label clinical study.

Purpose: The diabetic nephropathy is associated with oxidative stress and increases in pigment epithelium-derived factor (PEDF) level in the patient's blood. For the first time, authors investigated the effect of methylethylpiridinol addition to the therapy on oxidative status and pigment epithelium-derived factor concentrations, and examined the relationship between these indicators and clinical markers of pathology development.

Methods: Study design: open label randomized controlled trial study.

Neuroprotective effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline mediated via regulation of antioxidant system and inhibition of inflammation and apoptosis in a rat model of cerebral ischemia/reperfusion.

The aim of the study was the assessment of the neuroprotective potential of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (DHQ) and its effect on inflammation, apoptosis, and transcriptional regulation of the antioxidant system in cerebral ischemia/reperfusion (CIR) in rats. The CIR rat model was constructed using the bilateral common carotid artery occlusion followed by reoxygenation. DHQ was administered at a dose of 50 mg/kg for three days.

Activity of Antioxidant Defense Enzymes in Rats with Experimental Allergic Encephalomyelitis.

We studied activities of antioxidant system enzymes in tissues of rats with experimental allergic encephalomyelitis. It was shown that the development of pathology is accompanied by deformation of the neurons and axonal degeneration, intensification of free radical oxidation, exhaustion of the reduced glutathione pool, and multidirectional changes in activities of antioxidant enzymes in rat tissues. The observed imbalance in the antioxidant defense system can be associated with excessive glutathione utilization in the glutathione transferase reaction and different severity of the pathological process in the brain and spinal cord.

[Effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on the intensity of free radical processes and the activity of oxidative metabolism enzymes under toxic liver injury in rats].

The effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of hepatocytes cytolysis (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase), parameters reflecting the state of oxidative status (intensity of biochemical luminescence and the content of diene conjugates), and the activity of oxidative metabolism enzymes (aconitate hydratase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) was studied in rats with CCl4-induced liver injury. The results obtained in the course of the work demonstrated the ability of the test compound to reduce the severity of oxidative stress and liver cells damage, as well as to change the activity of aconitate hydratase and NADP-generating enzymes in the direction of control values. 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline was more effective in normalizing CCl4-induced changes of the analyzed parameters that Carsil used as a reference compound.

Transcriptional Regulation of Antioxidant Enzymes Activity and Modulation of Oxidative Stress by Melatonin in Rats Under Cerebral Ischemia / Reperfusion Conditions.

The article studies the effect of melatonin on the intensity of free radical oxidation, the functioning of the enzymatic components of the antioxidant system and their transcriptional regulation in rats with experimental cerebral ischemia/reperfusion of the brain. The development of ischemia/reperfusion was characterized by the activation of apoptotic processes and the accumulation of mRNA of the genes Sod1, Cat, Gpx1, Gsr, Hif-1α, Nrf2, Nfkb2, and Foxo1 in the rats' brains. The use of melatonin in the presence of the pathological induction led to a change in these parameters towards the control values.

Activity of Glutathione Antioxidant System and NADPH-Generating Enzymes in Rats with Experimental Rheumatoid Arthritis.

Induction of rheumatoid arthritis in rats was accompanied by an increase in diene conjugate content and glutathione reductase and glutathione peroxidase activities in muscles and blood serum. These changes can be related to mobilization of the glutathione reductase/glutathione peroxidase system coupled with intensification of free radical oxidation. In addition, activity of glucose-6-phosphodehydrogenase and NADP-dependent isocitrate dehydrogenase increased, which can be related to increased demand of NADPH for the glutathione reductase/glutathione peroxidase system.

[The dose-dependent influence of 3,5-dicarbometoxyphenylbiguanide on activity of the glutathione antioxidant system in heart and blood serum of rats with the experimental myocardial infarction].

Administration of a synthetic compound with predicted anti-ischemic and cardioprotective activity, 3,5-dicarbometoxyphenilbiguanide,--to rats with experimental myocardial infarction led to a decrease in the lipid peroxidation level, glutathione peroxidase activity, the level of reduced glutathione, activity of NADP-isocitrate dehydrogenase in the heart and blood serum, and also activity of glucoso-6-phosphate dehydrogenase in heart in comparison with their levels in untreated animals with myocardial infarction. This may be attributed to a decrease of free radical processes and reduction of antioxidant system loading. At the same time the increase glutathione reductase activity observed under these conditions in the heart and and blood serum probably associated with specific influence of 3,5-dicarbometoxyphenilbiguanide on this enzyme.