Oxidative stress is a key contributing factor in the complex degenerating cascade in Parkinson’s disease. The inhibition of MAO-B affords higher dopamine bioavailability and stops ROS formation. The incorporation of hydroxy and methoxy groups in the arylhydrazone moiety of a new series of 1,3-disubstituted benzimidazole-2-thiones could increase the neuroprotective activity. In vitro safety evaluation on SH-SY5Y cells and rat brain synaptosomes showed a strong safety profile. Antioxidant and neuroprotective effects were evaluated in H₂O₂-induced oxidative stress on SH-SY5Y cells and in a model of 6-OHDA-induced neurotoxicity in rat brain synaptosomes, where the dihydroxy compounds 3h and 3i demonstrated the most robust neuroprotective and antioxidant activity, more pronounced than the reference melatonin and rasagiline. Statistically significant MAO-B inhibitory effects were exerted by some of the compounds where again the catecholic compound 3h was the most potent inhibitor similar to selegiline and rasagiline. The most potent antioxidant effect in the ferrous iron induced lipid peroxidation assay was observed for the three catechols—3h and 3j, 3q. The catecholic compound 3h showed scavenging capability against superoxide radicals and antioxidant effect in the iron/deoxyribose system. The study outlines a perspective multifunctional compound with the best safety profile, neuroprotective, antioxidant and MAO-B inhibiting properties.

Oxidative stress is related to the pathogenesis of many neurodegenerative disorders, including

Introduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD). Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen. Materials and methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study. Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients’ plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases. Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals’ antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient’s oxidative status.

Drug resistance and toxicity are the most widespread limitations in the pursuit of sufficient antitumor effectiveness and successful control of oncological diseases, including colorectal cancer (CRC). Herein the objective was to investigate some hematological side effects of the chemotherapeutic regimen FOLFOX-4, their relation to dihydropyrimidine dehydrogenase (DPD) levels and the associated alterations in CRC patients’ plasma free-radical scavenging properties and extent of oxidative molecular damage. Thirty-eight patients with histologically confirmed CRC diagnoses, assigned to chemotherapy with the FOLFOX-4 regimen, were recruited. The diagnostic methods included a complete physical examination, blood routine test and general biochemistry. The DPD levels were assayed. The patients’ plasma free-radical scavenging properties and extent of molecular oxidative damage were determined by spectrophotometry and enhanced chemiluminescence. The clinico-pathological and demographics characteristics of the patients were in agreement with the reports from retrospective cohort studies. The FOLFOX-4 regimen induced a decrease in plasma free-radical scavenging properties and increased extent of lipid peroxidation. White blood cells, granulocytes and lymphocytes decreased significantly after the first cycle of the therapy. The patients’ DPD level decreased statistically significantly in the case of severe reduction (more than 25%) of white blood cells and granulocyte counts. The obtained data are in agreement with already known facts concerning the side effects of the FOLFOX-4 regimen and associated changes in redox homeostasis. Genetic predisposition to effectively metabolize and tolerate the applied therapy, i.e. DPD levels, could modulate some aspects of the observed changes in the aforementioned parameters.