Ulexite modulates the neurotoxicological outcomes of acetylferrocene-exposed rainbow trout.

In this study, the neuroprotective action potential by ulexite (UX) (18.75 mg/L) against acetylferrocene (AFC) (3.82 mg/L) induced neurotoxicity was aimed to investigate in brain tissues of Oncorhynchus mykiss. For this purpose, the effects on neurotoxicity markers, proinflammatory cytokines, antioxidant immune system, DNA, and apoptosis mechanisms were assessed on brain tissues in the 48-96  h of the 96- trial period. In this research, it was determined that brain-derived nerve cell growth factor (BDNF) level and acetylcholinesterase (AChE) activity were inhibited in the brain tissue compared to the control group by AFC. In addition, inhibition in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) values (which are antioxidant system biomarkers), and inductions in malondialdehyde (MDA) and myeloperoxidase (MPO) amounts (which are indicators of lipid peroxidation) were determined (p < 0.05) after exposure to AFC. And, while tumor necrosis factor-α (TNF-α) and IL-6 levels were increased in the AFC-exposed group, Nrf-2 levels were found to be remarkably decreased. Upregulation was also detected in 8-hydroxydeoxyguanosine (8-OHdG) and caspase-3 levels, which are related to DNA damage and apoptosis mechanism. On the contrary, UX (single/with AFC) suppressed the AChE and BDNF inhibition by AFC. Moreover, UX mitigated AFC-induced oxidative, inflammatory, and DNA damage and attenuated AFC-mediated neurotoxicity via activating Nrf2 signaling in fish. Collectively, our findings revealed that UX supplementation might exert beneficial effects and may be considered as a natural and promising neuroprotective agent against AFC-induced toxicity.

Borax exerts protective effect against ferrocene-induced neurotoxicity in Oncorhynchus mykiss.

BACKGROUND: In recent years, therapeutic targets and the development of new drugs have shifted research towards inflammatory and oxidative stress pathways. Ferrocene (FcH) is a stable, small molecule that exhibits immunostimulatory and anti-tumor properties by a different mechanism and is effective at low doses in oral administration. However, it was surprising that there has been no performed investigation using FcH on aquaculture. On the other hand, recent papers reveal the key biological functions and health benefits due to daily boron intake in animals and humans. Therefore, we investigated the neurotoxic damage potential of FcH and its related neurotoxicity action mechanism in aquatic environments. In addition, the protective potential of borax (BX, or sodium borate) were evaluated againt in vivo neurotoxicity by FcH. METHODS: Neurotoxicity assessment was performed in rainbow trout brain tissue, acutely under semi-static conditions via determining a vide range of parameters including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities as well as glutathione (GSH), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA levels), DNA damage (8-OHdG), apoptosis (caspase 3), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), nuclear factor erythroid-2 (Nrf-2), acetylcholinesterase (AChE) and brain-derived neurotrophic factor (BDNF) levels. In addition, the LC50 96 h level of FcH was determined for the first time in rainbow trout in this study. RESULTS: In the obtained results, while FcH caused inhibition in enzyme activities, it showed an inducing effect on MDA, MPO, BDNF, Nrf2, TNF-α and IL-6 levels. It was determined that this oxidative damage related alterations were significantly different (p < 0.05) in comparison between FcH treated and controls. Again, the LC50 96 h value in rainbow trout was determined as 11.73 mg/L, which is approximately 5% less than the value given for freshwater fish (12.3 mg/L). On the contrary, it was observed that BX has a mitigating effect on FcH-induced neurotoxicity. CONCLUSION: The present study suggests that borax may be useful for preventing or alleviating neurotoxicity induced by environmental contaminants or toxic chemicals.

The effect of N-acetylcysteine supplementation on the oxidative stress levels, apoptosis, DNA damage, and hematopoietic effect in pesticide-exposed fish blood.

Cysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N-acetylcysteine (NAC) were applied for a 4-day treatment period and compared with the group of the self-healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein-cholesterol [LDL-C], sodium, and potassium), were found to be importantly different among all groups at the P < 0.05 level, while 8-hydroxydeoxyguanosine and caspase-3 levels were determined to be high in the pesticide group but decreased significantly in NAC-treated groups ( P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0 mM NAC. NAC has an important therapeutic effect on pesticide-induced hematoxicity for fish in terms of all the data.

Borax Alleviates Copper-Induced Renal Injury via Inhibiting the DNA Damage and Apoptosis in Rainbow Trout.

The aim of this study was to determine the therapeutic potential of borax against copper in the kidney tissue of the rainbow trout fed with added borax (BX) (1.25, 2.5, and 5 mg/kg) and/or copper (Cu) (500,1000 mg/kg) contents. For this purpose, two treatment groups had designed, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzyme activities were determined. Besides, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine, 8-OHdG), caspase-3, and malondialdehyde (MDA) levels were assessed in kidneys of all treatment groups. In molecular pathway, hsp70, CYP1A, and antioxidant gene expression levels were determined. In the results of the analysis, antioxidant enzyme activity and gene expression were increased; 8-OHdG, caspase-3, and MDA levels were decreased in groups fed with borax supplemented feeds compared to the copper-treated group. The alterations among the groups were found as significant (p < 0.05). CYP1A and hsp70 gene expressions were upregulated in copper and copper combined groups (p < 0.05). The findings of present research showed that borax had alleviative effect on copper-induced toxicity and could be used as an antidote in fish nutrition.

Neuroprotective effects of dietary borax in the brain tissue of rainbow trout (Oncorhynchus mykiss) exposed to copper-induced toxicity.

We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein 70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide dismutase (sod), and catalase (cat)) parameters and immunohistochemically staining of 8-OHdG. Special fish feed diets were prepared for the trial. These diets contained different concentrations of borax (1.25, 2.5, and 5 mg/kg) and/or copper (500 and 1000 mg/kg) at the period of pre- and co-treatment strategies for 21 days. At the end of the treatment periods, brain tissue was sampled for each experimental group. As a result, the biochemical parameters were increased and AChE activity decreased in the copper and copper-combined groups in comparison with the control group and also with only borax applications (p < 0.05). We observed an increase or decrease in particular biochemical parameters for the borax group in every application and we established that borax had protective effect against copper toxicity by decreasing and/or increasing the relevant biochemical parameters in brain tissue of fish. The biochemical results of borax and its combinations corresponded to the observations of gene expression data, which similarly concluded that HSP70 and CYP1A genes were strongly induced by copper (p < 0.05). In addition, the expression levels of the sod, cat, and gpx genes in the fish brains exposed to borax and the borax combination groups were significantly higher than the only copper-treated groups. In conclusion, borax supplementation provided significant protection against copper-induced neurotoxicity in trout.