boron and Parkinson-Disease

Parkinson's disease (PD) is one of the most common forms of neurodegenerative diseases and research on potential therapeutic agents for PD continues. Rotenone is a neurotoxin that can pass the blood-brain barrier and is used to generate PD models in experimental animals. Boron is a microelement necessary for neural activity in the brain. Antioxidant, non-cytotoxic, anti-genotoxic, anti-carcinogenic effects of boric acid, the salt compound of boron has been reported before. Boronic acids have been approved for treatment by FDA and are included in drug discovery studies and pyridine boronic acids are a subclass of heterocyclic boronic acids used in drug design and discovery as substituted pyridines based on crystal engineering principles. The aim of our study was to determine the effect of 3-pyridinylboronic acid in rotenone-exposed zebrafish embryos, focusing on oxidant-antioxidant parameters and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes gclm, gclc, hmox1a, nqo1, and PD related genes, brain-derived neurotrophic factor, dj1, and tnfα. Zebrafish embryos were exposed to Rotenone (10 μg/l); Low Dose 3-Pyridinylboronic acid (100 μM); High Dose 3-Pyridinylboronic acid (200 μM); Rotenone + Low Dose-3-Pyridinylboronic acid (10 μg/l + 100 μM); Rotenone + High Dose-3-Pyridinylboronic acid (10 μg/l + 200 μM) in well plates for 96 h post-fertilization (hpf). Our study showed for the first time that 3-pyridinylboronic acid, as a novel sub-class of the heterocyclic boronic acid compound, improved locomotor activities, ameliorated oxidant-antioxidant status by decreasing LPO and NO levels, and normalized the expressions of bdnf, dj1, tnf⍺ and Nrf2 target genes hmox1a and nqo1 in rotenone exposed zebrafish embryos. On the other hand, it caused the deterioration of the oxidant-antioxidant balance in the control group through increased lipid peroxidation, nitric oxide levels, and decreased antioxidant enzymes. We believe that these results should be interpreted in the context of the dose-toxicity and benefit-harm relationship of the effects of 3-pyridinylboronic.

Topics: Animals; Antioxidants; Boron; Boronic Acids; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidants; Oxidative Stress; Parkinson Disease; Pyridines; Rotenone; Zebrafish

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the central nervous system. In different studies, it has been investigated that boric acid has positive effects on different mechanisms that are important in PD. The aim of our study was to investigate the pharmacological, behavioral and biochemical effects of boric acid on rats with experimental PD with Rotenone. For this purpose, Wistar-albino rats were divided into 6 groups. Only normal saline was applied subcutaneously (s.c) to the first control and sunflower oil to the second control group. Rotenone was administered (s.c) to 4 groups (groups 3-6) at a dose of 2 mg/kg for 21 days. Only rotenone (2mg/kg, s.c) was administered to the third group. Boric acid was administered intraperitoneally (i.p.) at 5 mg/kg, 10 mg/kg, and 20 mg/kg to groups 4, 5, and 6, respectively. During the study, behavioral tests were applied to the rats, and then histopathological and biochemical analyzes were performed from the sacrificed tissues. According to the data obtained, a statistically significant difference (p<0.05) was observed between the Parkinson's group and the other groups in motor behavior tests, excluding the catalepsy test. Boric acid exhibited dose-dependent antioxidant activity. As a result of the histopathological and immunohistochemical (IHC) examination, a decrease in neuronal degeneration was observed at the increasing doses of boric acid, while gliosis and focal encephalomalacia were rarely encountered. There was a significant increase in tyrosine hydroxylase (TH) immunoreactivity, especially in group 6, with a dose of 20 mg/kg of boric acid. From these results, we conclude that the dose-dependent effect of boric acid may protect the dopaminergic system with antioxidant activity in the pathogenesis of PD. However, the effectiveness of boric acid on PD needs further investigation in a larger, more detailed study using different methods.

Topics: Animals; Antioxidants; Boron; Disease Models, Animal; Neuroprotective Agents; Parkinson Disease; Rats; Rats, Wistar; Rotenone