Experimental study for in vitro prostate cancer treatment with microwave ablation and pulsed electromagnetic field.

This paper presents the findings of a comprehensive study exploring the synergistic effects arising from the combination of microwave ablation and pulsed electromagnetic field (PEMF) therapy on prostate cancer cells. The research encompassed five distinct experimental groups, with continuous electric field measurements conducted during the entire treatment process. Group 1 and Group 2, subjected to microwave power below 350 W, exhibited specific electric field values of 72,800 V/m and 56,600 V/m, respectively. In contrast, Group 3 and Group 4, exposed to 80 W microwave power, displayed electric field levels of approximately 1450 V/m, while remaining free from any observable electrical discharges. The migratory and invasive capacities of PC3 cells were assessed through a scratch test in all groups. Notably, cells in Group 3 and Group 4, subjected to the combined treatment of microwave ablation and PEMF, demonstrated significantly accelerated migration in comparison to those in Groups 1 and 2. Additionally, Group 5 cells, receiving PEMF treatment in isolation, exhibited decreased migratory ability. These results strongly suggest that the combined approach of microwave ablation and PEMF holds promise as a potential therapeutic intervention for prostate cancer, as it effectively reduced cell viability, induced apoptosis, and impeded migration ability in PC3 cells. Moreover, the isolated use of PEMF demonstrated potential in limiting migratory capacity, which could hold critical implications in the fight against cancer metastasis.

In this study, a new approach to treat prostate cancer by combining microwave ablation (MWA) and pulsed electromagnetic field (PEMF) therapy is explored. We used specific devices like rectangular waveguides for MWA and circular coils for PEMF. The energy sources utilized in the study comprised a magnetron tube system, similar to the microwave source found in a microwave oven, for generating microwaves, and a signal generator for producing PEMF. We used specialized equipment for MWA and PEMF to maintain controlled conditions, ensuring precise and reliable results. The research included testing various groups of prostate cancer cells exposed to different intensities of microwave power and magnetic flux density. The movement of cancer cells in different groups was examined through a wound healing assay, where cancer cells were placed on a flat surface, and we observed whether they filled the gap created by their movement. Interestingly, cells treated with both MWA and PEMF demonstrated faster movement compared to cells treated with MWA alone or PEMF alone. This combined treatment not only effectively decreased cell movement but also showed the potential cell death. The results showed that the combination of MWA and PEMF suggest a promising therapeutic strategy. The findings contribute to the development of precise and effective therapies that could enhance patient outcomes and quality of life. However, further research and validation are essential before translating these findings into clinical applications.

Choline chloride shows gender-dependent positive effects on social deficits, learning/memory impairments, neuronal loss and neuroinflammation in the lipopolysaccharide-induced rat model of autism.

The neuroprotective effects of choline chloride, an essential nutrient, a precursor for the acetylcholine and synthesis of membrane phospholipids, have been associated with neurological and neurodegenerative diseases. Its contribution to autism spectrum disorder, a neurodevelopmental disorder, remains unknown. Thus, we aimed to evaluate the effects of choline chloride on social behaviours, and histopathological and biochemical changes in a rat autism model. The autism model was induced by administration of 100 µg/kg lipopolysaccharide (LPS) on the 10th day of gestation. Choline chloride treatment (100 mg/kg/day) was commenced on PN5 and maintained until PN50. Social deficits were assessed by three-chamber sociability, open field, and passive avoidance learning tests. Tumour necrosis factor alpha (TNF-α), interleukin-2 (IL) and IL-17, nerve growth factor (NGF), and glutamate decarboxylase 67 (GAD67) levels were measured to assess neuroinflammatory responses. In addition, the number of hippocampal and cerebellar neurons and glial fibrillary acidic protein (GFAP) expression were evaluated. Social novelty and passive avoidance learning tests revealed significant differences in choline chloride-treated male rats compared with saline-treated groups. TNF-α, IL-2, and IL-17 were significantly decreased after choline chloride treatment in both males and females. NGF and GAD67 levels were unchanged in females, while there were significant differences in males. Histologically, significant changes in terms of gliosis were detected in hippocampal CA1 and CA3 regions and cerebellum in choline chloride-treated groups. The presence of ameliorative effects of choline chloride treatment on social behaviour and neuroinflammation through neuroinflammatory, neurotrophic, and neurotransmission pathways in a sex-dependent rat model of LPS-induced autism was demonstrated.

Novel multifunctional tacrine-donepezil hybrids against Alzheimer's disease: Design synthesis and bioactivity studies.

A series of tacrine-donepezil hybrids were synthesized as potential multifunctional anti-Alzheimer's disease (AD) compounds. For this purpose, tacrine and the benzylpiperidine moiety of donepezil were fused with a hydrazone group to achieve a small library of tacrine-donepezil hybrids. In agreement with the design, all compounds showed inhibitory activity toward both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values in the low micromolar range. Kinetic studies on the most potent cholinesterase (ChE) inhibitors within the series showed a mixed-type inhibition mechanism on both enzymes. Also, the docking studies indicated that the compounds inhibit ChEs by dual binding site (DBS) interactions. Notably, tacrine-donepezil hybrids also exhibited significant neuroprotection against H2O2-induced cell death in a differentiated human neuroblastoma (SH-SY5Y) cell line at concentrations close to their IC50 values on ChEs and showed high to medium blood-brain barrier (BBB) permeability on human cerebral microvascular endothelial cells (HBEC-5i). Besides, the compounds do not cause remarkable toxicity in a human hepatocellular carcinoma cell line (HepG2) and SH-SY5Y cells. Additionally, the compounds were predicted to also have good bioavailability. Among the tested compounds, H4, H16, H17, and H24 stand out with their biological profile. Taken together, the proposed novel tacrine-donepezil scaffold represents a promising starting point for the development of novel anti-ChE multifunctional agents against AD.

Prenatal Exposure to COVID-19 mRNA Vaccine BNT162b2 Induces Autism-Like Behaviors in Male Neonatal Rats: Insights into WNT and BDNF Signaling Perturbations.

The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential.

Heteronemin promotes iron-dependent cell death in pancreatic cancer.

The marine environment has been recognized as a prolific source of potent bioactive compounds with significant anticancer properties. Among these, heteronemin, a sesterterpenoid-type natural product, has shown promise. This study delves into the potential of heteronemin as a ferroptotic agent against pancreatic cancer, using the Panc-1 cell line as a model. The cytotoxic potential of heteronemin was assessed using cell viability assays. Furthermore, its effect on lipid peroxidation was determined spectrophotometrically, while the changes it induced in autophagy- and ferritin-related protein expressions were evaluated using immunoblotting techniques. Various cell-based tests were employed to scrutinize its anticancer efficacy. Heteronemin displayed a notable cytotoxic effect, reducing cell viability by 50% at a concentration of 55 nM. This cytotoxicity was discernibly linked to ferroptosis, as evidenced by the reversal of cell death upon treatment with the ferroptosis inhibitor, ferrostatin-1. Heteronemin treatment led to a marked increase in ferroptosis markers and malondialdehyde (MDA) levels. Conversely, the expression of glutathione peroxidase-4 (GPX4), a key anti-ferroptotic protein, was suppressed. Furthermore, significant modulations in the expression of ferritinophagy- and iron-related proteins such as Atg5, Atg7, FTL, STEAP3, and DMT-1 were evident post-treatment (p < 0.05). This study underscores the potential of heteronemin as a ferroptosis inducer in pancreatic cancer cells. Given its robust cytotoxicity, heteronemin emerges as a promising lead compound for further exploration in cancer therapeutics.

Regulation of tight junction proteins and cell death by peroxisome proliferator-activated receptor γ agonist in brainstem of hypertensive rats.

The decrease in tight junction proteins and their adapter proteins in the hypertensive brain is remarkable. Here, we aimed to investigate tight junction proteins and peroxisome proliferator-activated receptor (PPARγ) activation as well as inflammation factors and cell death proteins in the brainstem of hypertension models, namely spontaneously hypertensive rats (SHR) and borderline hypertensive rats (BHR). At first, SHR and BHR groups were treated with PPARγ agonist, pioglitazone. Then, occludin, claudin-1, claudin-2, claudin-12, ZO-1, and NF-κB p65 gene expression levels; pIKKß, NF-κB p65, TNF, IL-1ß, caspase-3, caspase-9 levels, and PARP-1 cleavage were evaluated. Significantly lower pIKKß, NF-κB p65, TNF, and IL-1ß levels were measured in pioglitazone-treated SHR. Results from this study confirm higher occludin (1.35-fold), claudin-2 (7.45-fold), claudin-12 (1.12-fold), and NF-κB p65 subunit (4.76-fold) expressions in the BHR group when compared to the SHR group. Pioglitazone was found effective in terms of regulating gene expression in SHR. Pioglitazone significantly increased occludin (8.17-fold), claudin-2 (2.41-fold), and claudin-12 (1.85-fold) mRNA levels, which were accompanied by decreased cleaved caspase-3, caspase-9 levels, PARP-1 activation, and proinflammatory factor levels in SHR (p ˂ 0.05). Our work has led us to conclude that alterations in tight junction proteins, particularly occludin, and cell death parameters in the brainstem following PPARγ activation may contribute to neuroprotection in essential hypertension.

Neuroprotective effect of dexpanthenol on rotenone-induced Parkinson's disease model in rats.

Parkinson's disease (PD) is the second most common and progressive neurodegenerative disease. This experimental study was designed to investigate the neuroprotective effects of dexpanthenol on antioxidant and anti-inflammatory processes in a rotenone-induced Parkinson's disease model in rats. Twenty-one male rats were randomly divided into 2 groups. The rotenone group (n = 14) was administered rotenone by intrastriatal injection, and the vehicle group (n = 7) was administered DMSO with the same application route. All animals underwent rotational movement testing with apomorphine injection 10 days later. Those with Parkinson's disease model were randomly divided into 2 groups. While 1 ml/kg of saline was applied to the saline group (n = 7), 500 mg/kg was administered to the dexpanthenol group intraperitoneally for 28 days. After 28 days, all rats were euthanized and brain tissue was removed. While striatal areas were evaluated immunohistochemically, brain MDA, TNF-α, and HVA levels were measured to evaluate their anti-oxidative and anti-inflammatory effects. In the dexpanthenol group, the total count (p < 0.001) and intensity (p < 0.001) of dopaminergic neurons in the striatal areas increased compared to the saline group. It was revealed that MDA (nmol/g) (p < 0.001) and TNF-α (pg/g) (p < 0.001) levels decreased in the dexpanthenol group, while HVA (ng/mg) levels increased (p < 0.01). This study suggests that dexpanthenol may have a neuroprotective effect by reducing neuronal loss, oxidative damage, and neuroinflammation in the striatum in rats.

The role of ion channels in the relationship between the immune system and cancer.

The immune system is capable of identifying and eliminating cancer, a complicated illness marked by unchecked cellular proliferation. The significance of ion channels in the complex interaction between the immune system and cancer has been clarified by recent studies. Ion channels, which are proteins that control ion flow across cell membranes, have variety of physiological purposes, such as regulating immune cell activity and tumor development. Immune cell surfaces contain ion channels, which have been identified to control immune cell activation, motility, and effector activities. The regulation of immune responses against cancer cells has been linked to a number of ion channels, including potassium, calcium, and chloride channels. As an example, potassium channels are essential for regulating T cell activation and proliferation, which are vital for anti-tumor immunity. Calcium channels play a crucial role when immune cells produce cytotoxic chemicals in order to eliminate cancer cells. Chloride channels also affect immune cell infiltration and invasion into malignancies. Additionally, tumor cells' own expressed ion channels have an impact on their behavior and in the interaction with the immune system. The proliferation, resistance to apoptosis, and immune evasion of cancer cells may all be impacted by changes in ion channel expression and function. Ion channels may also affect the tumor microenvironment by controlling angiogenesis, inflammatory responses, and immune cell infiltration. Ion channel function in the interaction between the immune system and cancer has important implications for cancer treatment. A possible method to improve anti-tumor immune responses and stop tumor development is to target certain ion channels. Small compounds and antibodies are among the ion channel modulators under investigation as possible immunotherapeutics. The complex interaction between ion channels, the immune system, and cancer highlights the significance of these channels for tumor immunity. The development of novel therapeutic strategies for the treatment of cancer will be made possible by unraveling the processes by which ion channels control immune responses and tumor activity. Hence, the main driving idea of the present chapter is trying to understand the possible function of ion channels in the complex crosstalk between cancer and immunoresponse. To this aim, after giving a brief journey of ion channels throughout the history, a classification of the main ion channels involved in cancer disease will be discussed. Finally, the last paragraph will focus on more recently advancements in the use of biomaterials as therapeutic strategy for cancer treatment. The hope is that future research will take advantage of the promising combination of ion channels, immunomodulation and biomaterials filed to provide better solutions in the treatment of cancer disease.

The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model.

Peripheral nerve damage is a significant clinical problem with limited therapeutic options. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic approach due to their regenerative potential. However, the underlying mechanisms by which ADSCs promote peripheral nerve regeneration remain unclear. In this study, we investigated the role of syndecan-1 and heat shock protein 70 (HSP-70) in mediating the regenerative effects of ADSCs on peripheral nerves. ADSCs were characterized and isolated from the adipose tissue of rats. In vitro experiments were conducted to evaluate the ability of ADSCs to secrete syndecan-1 and HSP-70 in response to stress conditions. To evaluate the therapeutic potential of ADSCs, rats with sciatic nerve injuries were treated with ADSCs and assessed for functional recovery, nerve regeneration, and changes in syndecan-1 and HSP-70 levels. Regeneration was evaluated with Electromyography (EMG) histology. The results showed that ADSCs could secrete syndecan-1 and HSP-70 in response to stress conditions. Furthermore, ADSC treatment significantly improved functional recovery and nerve regeneration and increased syndecan-1 and HSP-70 levels in the injured nerve. On the other hand, ADSCs make improvements histologically through the influence of Nerve growth factor (NGF), Malondialdehyde (MDA), and EMG.

Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral Changes in Male Neonatal Rats.

Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 µg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 µg/kg spike protein + 150 µg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment.

Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD. METHODS: Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively. RESULTS: In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function. CONCLUSION: In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model.

OBJECTIVE: This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. METHODS: This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. RESULTS: G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. CONCLUSION: In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

Rottlerin and genistein inhibit neuroblastoma cell proliferation and invasion through EF2K suppression and related protein pathways.

Neuroblastoma is one of the most common solid tumors in children younger than 1 year of age, with poor prognosis and survival rates. Therefore, novel molecular targets and therapeutic strategies are needed to prolong patient survival. For this purpose, we investigated the effects of rottlerin and genistein separately and in combination on neuroblastoma cells (SH-SY5Y, Kelly). First, the effects of rottlerin and genistein were investigated on cell proliferation. Different rottlerin (1-50 µM) and genistein (5-150 µM) doses were used as experimental groups compared to the control (DMSO/vehicle). The IC50 dose was found to be 5 µM for rottlerin and 30 µM for genistein (P < 0.0001). Other analyses, such as colony formation assays, annexin V/propidium iodide staining, matrigel invasion assays, and Western blot analysis, were performed with these doses and their combinations. To assess statistical significance, statistical analysis was conducted using the one-way ANOVA with the post hoc Tukey test. Our results showed that IC50 doses of rottlerin and genistein induced a significant reduction in cell proliferation, colony formation, and invasion in neuroblastoma cells (P < 0.0001). The combination of these doses increased the levels of inhibition of cell proliferation and invasion while decreasing the level of apoptosis (P 0.0001). Furthermore, these agents caused G1-cell cycle arrest in these cells. Our western blot data showed that rottlerin and genistein treatments markedly inhibit elongation factor 2 kinase (EF2K) and other pro-tumorigenic, metastatic proteins in neuroblastoma cells. These agents probably showed their anti-proliferative, anti-metastatic, and pro-apoptotic effects through EF2K downregulation. Our results suggested that rottlerin and genistein have inhibitory effects on cancer cell proliferation, invasion, and cell cycle and induce apoptosis in both cell lines. Combined treatment with rottlerin and genistein may be a viable approach and beneficial to neuroblastoma patients as the combined effect significantly suppresses the above-mentioned pathways.

N-acetyl cysteine: A new look at its effect on PTZ-induced convulsions.

INTRODUCTION/AIM: Epilepsy is widely investigated as a common neurological disease requiring pharmacologically effective agents. N-acetyl cysteine (NAC), has become a remarkable molecule with its role in both antioxidant and glutaminergic modulation. There are many points and processes waiting to be revealed regarding the role of NAC in epilepsy. MATERIALS AND METHODS: Pentylenetetrazole (PTZ) was administered to induce seizures in a total number of 48 Sprague-Dawley rats. 35 mg/kg PTZ dose as a sub-convulsive dose was administered to 24 animals to monitor EEG changes, while 70 mg/kg PTZ dose which was a convulsive dose was administered to 24 animals to determine seizure-related behavioral changes with the Racine's scale. 30 min before the seizure-induced procedure, NAC was administered at doses of 300 and 600 mg/kg as pretreatment to investigate anti-seizure and anti-oxidative effects. The spike percentage, the stage of convulsion, and the onset time of the first myoclonic jerk were evaluated to determine the anti-seizure effect. Furthermore, its effect on oxidative stress was determined by measuring both malondialdehyde (MDA) level and superoxide dismutase (SOD) enzyme activity. RESULTS: There was a dose-dependent reduction in the seizure stage and prolonged onset time of the first myoclonic jerk in rats with NAC pretreatment. EEG recordings resulted in a dose-dependent decrease in spike percentages. Moreover, the same dose-dependent changes were observed in oxidative stress biomarkers, both 300 mg/kg NAC and 600 mg/kg decreased MDA levels and ameliorated SOD activity. CONCLUSION: We can report that 300 mg/kg and 600 mg/kg doses of NAC are promising with their reducing effect on convulsions and have a beneficial effect by preventing oxidative stress. In addition, NAC has been also determined that this effect is dose-dependent. Detailed and comparative studies are needed on the convulsion-reducing effect of NAC in epilepsy.

Immunosuppressant Tacrolimus Treatment Delays Acute Seizure Occurrence, Reduces Elevated Oxidative Stress, and Reverses PGF2α Burst in the Brain of PTZ-Treated Rats.

It is still an urgent need to find alternative and effective therapies to combat epileptic seizures. Tacrolimus as a potent immunosuppressant and calcineurin inhibitor is emerging as promising drug to suppress seizures. However, there are few reports applying tacrolimus to epilepsy and providing data for its antiseizure properties. In this study, we investigated the antiseizure effects of 5 and 10 mg/kg doses of tacrolimus treatment priorly to pentylenetetrazol (PTZ) induction of seizures in rats. As an experimental design, we establish two independent rat groups where we observe convulsive seizures following 70 mg/kg PTZ and sub-convulsive seizures detected by electroencephalography (EEG) following 35 mg/kg PTZ. Thereafter, we proceed with biochemical analyses of the brain including assessment of malondialdehyde level as an indicator of lipid peroxidation and detection of superoxide dismutase (SOD) enzyme activity and PGF2α. Tacrolimus pre-treatment dose-dependently resulted in lesser seizure severity according to Racine's scale, delayed start-up latency of the first myoclonic jerk and attenuated the spike percentages detected by EEG in seizure-induced rats. However, only the higher dose of tacrolimus was effective to restore lipid peroxidation. An increase in SOD activity was observed in the PTZ group, mediated by seizure activity per se, however, it was greater in the groups that received treatment with 5 and 10 mg/kg of Tacrolimus. PGF2α bursts following PTZ induction of seizures were reversed by tacrolimus pre-treatment in a dose-dependent manner as well. We report that the well-known immunosuppressant tacrolimus is a promising agent to suppress seizures. Comparative studies are necessary to determine the possible utilization of tacrolimus in clinical cases.

Epigallocatechin-3-gallate and resveratrol attenuate hydrogen peroxide induced damage in neuronal cells.

PURPOSE: The purpose of this study is to investigate how the antioxidants resveratrol and epigallocatechin-3-gallate (EGCG) protect SH-SY5Y cells against damage caused by hydrogen peroxide (H2O2). METHODS: SH-SY5Y cells were pretreated with EGCG and resveratrol at concentrations of 0.1 µM, 1 µM, and 10 µM, individually and in various combinations. Cells were exposed to 250 µM H2O2 for 1-hour following a 24-hour pretreatment. The effects of EGCG and resveratrol on cellular survival against hydrogen peroxide toxicity were evaluated with the MTS. Caspase 3 levels were measured with caspase 3 ELISA test for evaluating survival. The clonogenic test was utilized to assess the colony forming capacity. RESULTS: The MTS test revealed that pretreatment of SH-SY5Y cells for 24 hours with EGCG and Resveratrol enhanced cellular survival against hydrogen peroxide damage at all dosages (p < 0.005). The caspase 3 ELISA test revealed that EGCG and resveratrol statistically substantially decreased caspase 3 levels and improved cellular survival via the caspase 3 pathway (p < 0.005). The clonogenic test findings show that resveratrol and EGCG statistically boost SH-SY5Y cells' potential to form colonies (p<0.005). CONCLUSIONS: By reducing caspase 3 levels in exposure to hydrogen peroxide damage, EGCG and resveratrol promote cellular viability (Tab. 1, Fig. 3, Ref. 37). Text in PDF www.elis.sk Keywords: epigallocatechin-3-gallate, resveratrol, hydrogen peroxide, neurodegeneration.

The Healing Effect of Digoxin on Peripheral Nerve Damage and Its Relation to IL-17/IL-10.

AIM: To demonstrate the curative effect of digoxin on peripheral nerve damage with its anti-inflammatory role on interleukin (IL)-17. MATERIAL AND METHODS: The study was conducted with 30 male Sprague Dawley albino mature rats, of which 10 formed the control group, 10 were surgically treated and administered saline (group S), and another 10 were surgically treated and administered digoxin (group D). Motor functions and immunohistochemical and biochemical variables of the rats were assessed after therapy. RESULTS: The amplitude of the inclined plane test scores and the compound muscle action potential levels were greater in group D than in group S. Likewise, there were higher nerve growth factor percentages, higher axon counts, and lower fibrosis score percentages in group D than is group S. Lastly, lower tissue malondialdehyde and plasma IL-17 levels were determined in group D, while the IL-10 level was higher. CONCLUSION: Digoxin contributes to nerve healing and neuroprotective effect by demonstrating its anti-inflammatory effect on IL-17. It can be considered an adjunctive therapy for peripheral nerve injury.

Demonstration of the protective effect of propofol in rat model of cisplatin-induced neuropathy.

Cisplatin is commonly used in the treatment of lung, genitourinary, and gastrointestinal cancers. Peripheral neuropathy is the most important side effect, leading to a decrease in the dose of cisplatin or its complete cessation in the early period. 16 rats were given cisplatin at a dose of 2.5 mg/ kg/day twice a week for 4 weeks to induce neuropathy model. The rats taking Cisplatin were divided into 2 groups. Group 1 rats (n = 8) were given 1 ml/kg/day 0.9 % NaCl intraperitoneally, and Group 2 rats were given 10 mg/kg/day Propofol intraperitoneally daily for 4 weeks. The remaining 8 rats served as the control group. At the end of the study, all animals were tested for motor functions. Blood samples were collected for the measurement of plasma lipid peroxidation (malondialdehyde; MDA), tumor necrosis factor (TNF-α), glutathione (GSH), IL-6 and HSP-70 levels. Electromyography findings revealed that compound muscle action potential (CMAP) amplitude was significantly higher in the cisplatin-Propofol group than in the cisplatin-saline group. Also, cisplatin-Propofol treated group showed significantly lower TNF-α, MDA and IL-6 levels and higher GSH and HSP-70 levels than cispalatin-Saline group (p < 0.01, p < 0.001). In addition, while the CMAP latency was decreased in the propofol group, the CMAP amplitude was increased, and a significant improvement was observed in the Inclined test scores. Besides, histological examinations showed an increase in axon diameter and NGF expression with Propofol treatment. This study demonstrated that Propofol exerts protective activity against cisplatin-induced neurotoxicity by increasing endogenous antioxidants and reducing lipid peroxidation and inflammation (Tab. 3, Fig. 4, Ref. 30). Text in PDF www.elis.sk Keywords: cisplatin, neuropathy, propofol, oxidative damage, inflammation.

Effects of prenatal testosterone exposure on the development of autism-like behaviours in offspring of Wistar rats.

BACKGROUND: A neurodevelopmental disease, autism spectrum disorder (ASD) occurs in males three times more commonly than girls. Higher prenatal testosterone exposure may result in autistic-like behaviour in boys, according to earlier research. It is unclear how fetal testosterone affects the development of autism. In this study, we tested the hypothesis that prenatal testosterone exposure in an animal model may result in autistic behaviours by modifying serotonin, dopamine, IGF-1 and oxytocin levels. MATERIALS AND METHODS: Group 1 (control, n = 6) and Group 2 (testosterone undecanoate, n = 6) of female rats were randomly assigned. For 2-3 days during the oestrus cycle, female rats were housed with a reproductive male (three females/one male). On the 10th day of gestation, rats in Group 1 received 1 ml/kg% 0.9 NaCl saline, whereas rats in Group 2 received 250 mg/kg testosterone undecanoate. Until weaning on postnatal day 21 (P21), the mothers were permitted to care for their pups. On P21, 40 littermates-10 male and female for control and 10 male and female from mothers that exposed to testosterone-were arbitrarily split up and housed. On P50, these mature rats were tested for their behaviour. The rats were then sacrificed. The brain tissue was subjected to histological examinations as well as biochemical tests for homovanillic acid (HVA), 5-Hydroxyindoleacetic acid (5-HIAA), oxytocin and insulin-like growth factor-1 (IGF-1). RESULTS: The groups differed significantly in the behavioural examinations (three-chamber social test, passive avoidance learning analysis, open field test), with the testosterone-exposed groups exhibiting autistic symptoms to a higher extent. When compared with the control groups, testosterone exposure caused significant histological changes in the hippocampus CA1 and CA3 areas, including gliosis and cell death of neurons. In the testosterone-exposed groups, HVA, 5-HIAA and IGF-1 tissue expressions in the brain elevated, whereas oxytocin levels reduced. These findings point to a potential connection between neurodevelopmental disorders like ASD and exposure to testosterone during gestation. CONCLUSION: Overall, we revealed that prenatal testosterone exposure led to autistic traits by elevating serotonin, dopamine and IGF-1 levels while lowering oxytocin levels.