Diethylhexyl phthalate exposure amplifies oxidant and inflammatory response in fetal hyperglycemia model predisposing insulin resistance in zebrafish embryos.

Exposure of zebrafish embryos to glucose is a suitable model for the fetal hyperglycemia seen in gestational diabetes. Diethylhexyl phthalate (DEHP), which is considered an endocrine-disrupting chemical, is one of the most common phthalate derivatives used in stretching plastic and is encountered in every area where plastic is used in daily life. In the present study, the effects of DEHP on pathways related to insulin resistance and obesity were examined in zebrafish embryos exposed to glucose as a fetal hyperglycemia model. Zebrafish embryos were exposed to DEHP, glucose, and glucose + DEHP for 72 h post-fertilization (hpf), and developmental parameters and locomotor activities were monitored. At 72 hpf ins, lepa, pparγ, atf4a, and il-6 expressions were determined by RT-PCR. Glucose, lipid peroxidation (LPO), nitric oxide (NO) levels, glutathione S-transferase (GST), superoxide dismutase (SOD), and acetylcholine esterase (AChE) activities were measured spectrophotometrically. Compared with the control group, glucose, LPO, GST activity, il6, and atf4a expressions increased in all exposure groups, while body length, locomotor, and SOD activities decreased. While AChE activity decreased in the DEHP and glucose groups, it increased in the glucose + DEHP group. Although glucose exposure increased pparγ and lepa expressions, DEHP significantly decreased the expressions of pparγ and lepa both in the DEHP and glucose + DEHP groups. Our findings showed that DEHP amplified oxidant and inflammatory responses in this fetal hyperglycemia model, predisposing insulin resistance in zebrafish embryos.

Panoramic dental X-ray exposure leads to oxidative stress, inflammation and apoptosis-mediated developmental defects in zebrafish embryos.

Panoramic x-ray units are widely used in dental radiodiagnostics. Patients are exposed to relatively low radiation doses with panoramic imaging, but considering lifetime frequency of exposure, even a small risk can have serious health consequences. Our aim was to assess the effects of panoramic x-rays at two different exposure times on developing zebrafish embryos, focusing on oxidative stress, inflammation, apoptotic pathways, and development. Zebrafish embryos were divided into three groups: control, standard panoramic (SPE, 5.5 s exposure time) and pedodontic panoramic x-ray group (PPE, 4.8 s exposure time). Optically stimulated luminescence dosimeters were used to measure absorbed doses. Mean radiation doses for SPE and PPE were 7.83 mSv and 5.83 mSv respectively. At the end of 96 h post-fertilization, lipid peroxidation (LPO), nitric oxide (NO), reduced glutathione (GSH), glutathione S-transferase and superoxide dismutase were measured in the embryos. Expressions of genes related with inflammation (tnfα, il6, ill15, il21), immunoregulation (ifng) and apoptosis (p53, bax, casp2, casp3, casp8) were determined by RT-PCR. Even at reduced doses at high-speed mode, developmental toxicity was observed in both groups as evidenced by decreased pigmentation, yolk sac oedema, and spinal curvature. While deterioration of oxidant-antioxidant balance, suppression of immune response, induction of inflammation and apoptosis were observed through increased LPO, NO, decreased GSH, ifng, and increased expressions of genes related with inflammation and apoptosis, these effects were more pronounced in the SPE group. These results demonstrate the influence of exposure time and indicate the need for further consideration of optimal panoramic modes from a radiation-induced damage perspective.

3-Pyridinylboronic Acid Ameliorates Rotenone-Induced Oxidative Stress Through Nrf2 Target Genes in Zebrafish Embryos.

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.