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. Wistar rats, divided into 4 groups were used in the study: sham-operated animals; animals with CIR caused by occlusion of the common carotid arteries and subsequent removal of the occlusions; rats treated with BHDQ at a dose of 50 mg/kg in the presence of pathology; sham-operated animals treated with BHDQ. The analysis of the state of energy metabolism in the brain, the level of the S100B protein and the histological assessment of the brain tissue were carried out. The antioxidant potential of BHDQ was assessed by measuring biochemiluminescence parameters, analysing the level of 8-isoprostane, products of lipid and protein oxidation, concentration of α-tocopherol and citrate, and aconitate hydratase activity during CIR in rats. A study of the effect of BHDQ on the regulation of the enzymatic antioxidant system and the inflammatory processes was performed. We demonstrated that BHDQ has a neuroprotective effect in CIR, reducing histopathological changes in the brain, normalizing pyruvate and lactate concentrations, and the transcripts level of Hif-1α gene. The positive effect of BHDQ was probably due to its antioxidant and anti-inflammatory activity, manifested in a decrease in the parameters of the oxidative stress, decreased mRNA of proinflammatory cytokines and NF-κB factor genes. In addition, BHDQ reduced the load on antioxidant protection enzymes, contributing to a change in their activities, decreased the level of antioxidant gene transcripts and expression of Nrf2 and Foxo1 factors toward control. Thus, BHDQ exhibited a neuroprotective effect due to a decrease in the level of oxidative stress and inflammation and the normalization of redox homeostasis on CIR in rats.

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.

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. Histological staining was performed using hematoxylin and eosin. The level of S100B protein, 8-hydroxy-2-deoxyguanosine, and 8-isoprostane was assessed using an enzyme immunoassay. The intensity of apoptosis was assessed based on the activity of caspases and DNA fragmentation. The activity of enzymes was measured spectrophotometrically, the level of gene transcripts was assessed by real-time PCR. DHQ reduced the histopathological changes and normalized levels of S100B, lactate, pyruvate, and HIF-1 mRNA in the CIR rat model. In addition, DHQ decreased the oxidative stress markers in animals with a pathology. The tested compound also inhibited inflammation by decreasing the activity of myeloperoxidase, expression of interleukins and Nfkb2. DHQ-treated rats with CIR showed decreased caspase activity, DNA fragmentation, and AIF expression. DHQ changed activity of antioxidant enzymes to the control values, decreased the expression of Cat, Gsr, and Nfe2l2, which was overexpressed in CIR, and activated the expression of Sod1, Gpx1, Gsta2, and Foxo1. DHQ showed a neuroprotective effect on CIR in rats. The neuroprotective effect involve mechanisms such as the inhibition of oxidative stress, leading to a reduction in the inflammatory response and apoptosis and the modulation of the antioxidant defense components.

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. The received data necessitate the search for compounds that can prevent inhibition of antioxidant system components in order to analyze the possibility of their use in the treatment of multiple sclerosis.

[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]. / Vozdeistvie 6-gidroksi-2,2,4-trimetil-1,2-digidro-khinolina na intensivnost' svobodnoradikal'nykh protsessov i aktivnost' fermentov okislitel'nogo metabolizma pri toksicheskom porazhenii pecheni u krys.

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. The tendency to normalize the state of oxidative status and enzyme activity of oxidative metabolism can attributed to hepatoprotective and antioxidant properties of the tested compound.

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 content of reduced glutathione in muscles and blood serum decreased, probably, due to its utilization for ROS neutralization. Glutathione transferase activity decreased in rheumatoid arthritis, which can be related to shortness of reduced glutathione developing during oxidative stress. The observed shifts in parameters of free radical homeostasis in rheumatoid arthritis are probably associated with intensification of free radical oxidation.

[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.