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. Six groups of animals were formed for our experiment, each with 12 animals. These were: a control group, animals with rotenone-induced PD, rats with PD given HTHQ at a dose of 50 mg/kg, rats with PD given HTHQ at a dose of 25 mg/kg, animals with pathology who were administered a comparison drug rasagiline, and control animals who were administered HTHQ at a dose of 50 mg/kg. The study results indicate that administering HTHQ led to a significant decrease in oxidative stress in PD rats. The enhanced redox status in animal tissues was linked with the recovery of antioxidant enzyme activities and NADPH-generating enzyme function, as well as an upsurge in the mRNA expression levels of antioxidant genes and factors Nrf2 and Foxo1. Administering HTHQ to rats with PD normalized the chaperone-like activity and mRNA levels of heat shock protein 70. Rats treated with the compound displayed lower apoptosis intensity when compared to animals with pathology. Therefore, owing to its antioxidant properties, HTHQ demonstrated a beneficial impact on the antioxidant system, resulting in decreased requirements for chaperone activation and the inhibition of apoptosis processes triggered in PD. HTHQ at a dose of 50 mg/kg had a greater impact on the majority of the examined variables compared to rasagiline.

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. Laboratory animals were divided into 4 groups: control group; animals with RA; animals injected intraperitoneally with SkQ1 at the doses of 1250 and 625 nmol/kg, respectively, every 24 h for 8 days starting from day 7 of RA development. Tissue samples for analysis were collected on day 15 of the experiment. Erythrocyte sedimentation rate, the content of circulating immune complexes, and the concentration of class A, M, and G immunoglobulins were determined by enzyme immunoassay. The intensity of free radical-induced oxidation was evaluated based on the assessment of the iron-induced biochemiluminescence, diene conjugate content, and activity of aconitate hydratase. Enzymatic activity and metabolite content in the tissue samples were analyzed spectrophotometrically. It was shown that the development of RA was associated with an increase in the manifestation of immune response markers and intensity of free radical-induced oxidation, as well as with disruption of the AOS functioning and activation of NADPH-generating enzymes. SkQ1 administration resulted in a dose-dependent changes in the oxidative status indicators towards the control values and normalization of the immune status parameters. SkQ1 decreased the level of mitochondrial ROS, resulting in the suppression of the inflammatory response, which might cause inhibition of free radical generation by immunocompetent cells and subsequent mitigation of the oxidative stress severity in the tissues.

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. These alterations promoted an improvement in motor coordination scores and increased tyrosine hydroxylase levels, whereas histopathological changes in the brain tissue of the experimental animals were attenuated. HTHQ exhibited greater effectiveness than the comparative drug rasagiline based on the majority of variables.

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. In addition, the introduction of the hormone was accompanied by a decrease in lactate content, the level of lipoperoxidation products and oxidative modification of proteins, indicators of biochemiluminescence in the brain and blood serum. At the same time, there was a shift in the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which increased in the presence of a pathology, towards the control values. The revealed changes may be accounted for by antioxidant and neuroprotective properties of melatonin, which provided a decrease in the degree of mobilization of the protective systems in animal organism.