Anticonvulsant effect of glycitin in pentylenetetrazol induced male Wistar rat model by targeting oxidative stress and Nrf2/HO-1 signaling.

Epilepsy, characterized by recurrent seizures, poses a significant health challenge globally. Despite the availability of anti-seizure medications, their adverse effects and inadequate efficacy in controlling seizures propel the exploration of alternative therapeutic measures. In hypothesis, glycitin is a phytoestrogenic compound found in soybeans and due to its estrogenic properties may have anti-epileptic and neuroprotective effects. This study investigates the potential anti-epileptic properties of glycitin in the context of pentylenetetrazol (PTZ) induced seizures in male Wistar rats. The rats were pretreated with varying doses of glycitin (5, 10, and 20 mg/kg) before PTZ (35 mg/kg) administration, and assessments included behavioral observations and histological evaluation via hematoxylin and eosin (H&E) staining. Additionally, oxidative stress markers, such as malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels, were quantified to examine glycitin's impact on oxidative stress. Molecular analysis was conducted to assess the activation of the Nuclear factor erythroid 2-related factor (Nrf2)/Heme oxygenase 1 (HO-1) signaling pathway. Results indicated that glycitin pretreatment effectively mitigated PTZ-induced convulsive behaviors, supported by histological findings from H&E staining. Furthermore, glycitin administration led to significant alterations in MDA, GPx, and SOD levels, suggestive of its ability to modulate oxidative stress. Notably, glycitin treatment induced activation of the Nrf2/HO-1 signaling pathway. These findings underscore the potential of glycitin as an anticonvulsant agent, elucidating its mechanism of action through histological protection, modulation of oxidative stress markers, and activation of the Nrf2/HO-1 signaling pathway.

Selegiline Improves Cognitive Impairment in the Rat Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurological disorder characterized by cognitive decline. This study was undertaken to evaluate the effects of selegiline (SEL) against AD-induced cognitive deficits and explore the possible involved mechanisms. AD was induced by unilateral intracerebroventricular (U-ICV) injection of 5 µg of amyloid beta1-42 (Aß1-42), and oral administration of SEL (0.5 mg/kg/day) was performed for 30 consecutive days. Aß injection resulted in spatial cognitive decline, as demonstrated by a decrease in the time spent in the target zone on the probe day (P < 0.01) in the Barnes maze test (BMT). This spatial cognitive decline was associated with disrupted synaptic plasticity, as indicated by reductions in both components of hippocampal long-term potentiation (LTP), namely population spike amplitude (P < 0.001) and field excitatory postsynaptic potential (P < 0.001). On the other hand, the injection of Aß resulted in oxidative stress by decreasing total thiol group (TTG) content and increasing malondialdehyde (MDA) levels in the rat plasma (P < 0.001). Additionally, the number of healthy cells in the hippocampal dentate gyrus (DG) and CA1 regions was reduced in AD rats (P < 0.001). However, oral administration of SEL improved spatial cognitive decline in the Aß-induced AD rats. The results suggest that improvement of neuroplasticity deficiency, regulation of oxidant/antioxidant status, and suppression of neuronal loss by SEL may be the mechanisms underlying its beneficial effect against AD-related spatial cognitive impairment.

Protective effects of selegiline against amyloid beta-induced anxiety-like behavior and memory impairment.

BACKGROUND: Alzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1-42 (Aß1-42). METHODS: Oral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open-field, elevated plus-maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety-like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively. RESULTS: The results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative-antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative-antioxidant status in AD rats. CONCLUSIONS: These findings provide evidence that SEL may alleviate anxiety-like behavior and cognitive deficits induced by Aß through modulation of oxidative-antioxidant status.

Cacao consumption improves passive avoidance memory impairment in a rat model of Alzheimer's disease: the role of hippocampal synaptic plasticity and oxidative stress.

Introduction: Alzheimer's disease (AD) causes progressive loss of cognitive function and synaptic plasticity, which is the most common form of dementia. The present study was designed to scrutinize the effects of cacao on passive avoidance memory function and to identify the roles of hippocampal synaptic plasticity and oxidative stress in an AD rat model induced by unilateral intracerebroventricular (UICV) injection of amyloid-beta (Aß). Methods: Oral administration of cacao (500 mg/kg/ day) was given for 2 consecutive months. A memory retention test was conducted 24 h after passive avoidance training was completed. Subsequently, the amplitude of population spike (PS) and slope of field excitatory postsynaptic potentials (fEPSPs) were assessed at hippocampal long-term potentiation (LTP) in perforant pathway-dentate gyrus (PP-DG) synapses. Moreover, total thiol group (TTG) and malondialdehyde (MDA) concentrations were evaluated in the plasma. Furthermore, compact Aß plaques were detected in the hippocampal DG by performing Congo red staining. Results: As a result of AD induction, passive avoidance memory was impaired; also, reduced fEPSP slopes, PS amplitudes, and content of TTG, and increase in MDA levels in the rats were observed. In contrast, cacao treatment ameliorated passive avoidance memory impairment, improved hippocampal LTP impairment, modulated oxidative-antioxidative status, and delayed Aß plaques production in AD rats. Disscussion: Conclusively, cacao alleviates Aß-induced cognitive deficit, probably by the amelioration of hippocampal LTP impairment, modulation of oxidative-antioxidative status, and inhibition of Aß plaque accumulation.

Effect of Duvelisib, a Selective PI3K Inhibitor on Seizure Activity in Pentylenetetrazole-Induced Convulsions Animal Model.

Epilepsy is one of the most common neurological diseases, which is caused by abnormal brain activity. A wide variety of studies have shown the importance of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in epilepsy pathogenesis. Duvelisib (DUV) is a selective inhibitor of PI3K. The present study investigated the anticonvulsant potential of DUV in a rat model of pentylenetetrazole (PTZ)-induced convulsions. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with DUV at different doses of 5 and 10 mg/kg, or vehicle 30 minutes prior to PTZ (70 mg/kg, IP) treatment. Based on Racine's scale, behavioral seizures were assessed. The results showed that pretreatment with DUV prolonged the seizure stages according to the Racine scale, significantly decreased the duration of general tonic-clonic seizure and reduced the number of myoclonic jerks (P < .05). In conclusion, we found that PI3K antagonist DUV significantly reduced PTZ-induced seizures, indicating that DUV exerts an anticonvulsant effect by inhibiting PI3K signaling pathway.

Effect of Elettaria cardamomum L. on hormonal changes and spermatogenesis in the propylthiouracil-induced hypothyroidism male BALB/c mice.

INTRODUCTION: Spermatogenesis is significantly influenced by the thyroid gland. Thyroid disorders can be caused by a variety of factors. Traditionally, Ellettaria cardamomum has been used to treat a variety of ailments. The effects of E. cardamomum extract (ECE) on spermatogenesis in hypothyroid mice were investigated in this study. METHODS: In this study 42 male mice, weighing (25-35 g) were randomly divided in six groups: control group (taking normal saline, 0.5 mL/day, by oral gavage [P.O.]), hypothyroid group (taking 0.1% propylthiouracil in drinking water for 2 weeks), hypothyroid groups treated by levothyroxine (15 mg/kg/day, P.O.) and hypothyroid groups treated by ECE (100, 200 and 400 mg/kg/day, P.O.). After the end of experiments the mice were anaesthetised and blood samples were collected for hormonal analysis. RESULTS: The sperm count and microscopic studies of testes were done also. Our results showed that the T3 , T4 , testosterone levels and spermatogenesis in hypothyroid animals decreased and thyroid-stimulating hormone, follicle-stimulating hormone and luteinizing hormone increased compared with control group. Treatment by ECE reverse these effects in comparison with hypothyroid group. CONCLUSIONS: According to our findings, the ECE may stimulates thyroid gland function and increases testosterone and spermatogenesis.

Maternal long-term inhalation exposure to perchloroethylene and prenatal teratogenicity: morphometric, hormonal, and histological study.

Some commonly used chemicals have teratogenic effects. Perchloroethylene (PCE) is a liquid that is widely used in various industries and drying clothes. In this study, the teratogenic effects of PCE in rat embryos were investigated. In this experimental study, 32 adult Wistar female rats in the weight range of 230-250 g were used. Female rats were randomly divided into 4 groups (n = 8). Control group (without PCE inhalation), experimental group G(I) (exposed to PCE 18 days prior to mating), experimental group G(II) (exposed to PCE 18 days after mating) and experimental group G(III) (exposed to PCE 18 days before and 18 days after mating). Pregnant rats were anesthetized on the 18th day of gestation and then serum and embryos were removed for the required studies. Embryos were examined for number, weight, sex, morphometric parameters of organs, and tissue samples were prepared for histological studies. Serum isolated from dams were evaluated for sexual and gonadal hormones. The results of this study showed that PCE has teratogenic effects on rat embryos. Infertility and reduced birth rate were other effects of PCE in rats. PCE has teratogenic effects and impairs the reproductive system of rats.

Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Protective efficacy of dark chocolate in letrozole-induced ovary toxicity model rats: hormonal, biochemical, and histopathological investigation.

OBJECTIVE: To assess the protective effect of dark chocolate (DC) on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODS: In this experimental study, 32 female Wistar rats, weighing (200 ± 20) g, were randomly categorized into 4 groups including control, letrozole (1 mg·kg·d), metformin (500 mg·kg·d) along with letrozole, and DC (500 mg·kg·d) along with letrozole for 28 d by oral gavage. Twenty-four hours after the last supplementation, direct blood sampling was taken from the heart to obtain blood serum for evaluation of sex hormones and gonadotropins, oxidative parameters, inflammatory cytokines, and ovarian tissue was examined for histology. RESULTS: The DC treatment significantly improved PCOS signs, as demonstrated by the significant restoration of ovarian morphology and physiological functions as compared with the letrozole group. DC treatment also decreased ovarian interleukin-1ß and tumor necrosis factor-α levels and improved total oxidative/antioxidative status as compared with the letrozole group. CONCLUSIONS: Treating the animals with DC could alleviate the PCOS symptoms and reduced the toxic effects of letrozole in the ovary. This effect may mediate through antioxidant and antiinflammatory properties.

Interplay between polycystic ovary syndrome and hypothyroidism on serum testosterone, oxidative stress and StAR gene expression in female rats.

INTRODUCTION: Endocrine disorders such as polycystic ovary syndrome (PCOS) and hypothyroidism can cause infertility. There are evidence that they happen jointly in some circumstances. It still remains unknown, how these two illnesses interact and influence the body. METHODS: Accordingly, a five-group was designed, first is the control group, followed by the PCOS group. Estradiol valerate (EV) induced PCOS, the second group had only PCOS and the third, fourth and fifth groups were given varied dosages of propylthiouracil (PTU) to cause hypothyroidism after induction of PCOS. Steroidogenic acute regulatory protein (StAR) expression was measured in the ovaries, and serum was obtained to determine testosterone levels, as well as superoxide dismutase (SOD) as an antioxidant and malondialdehyde (MDA) as an oxidant. RESULTS: Based on radioimmunoassay data, testosterone levels were significantly higher in the PCOS group than the control group, and significantly lower (p Ë‚ .05) in PTU groups comparing with the PCOS group. According to the quantitative real-time polymerase chain reaction (qRT-PCR) data, the same results were obtained for the StAR gene as well. The data also indicated a positive correlation between these two. Although both oxidant and antioxidant level increased in PCOS group compared than control group, after hypothyroidism, oxidant level increased significantly (p Ë‚ .05), meanwhile antioxidant level decreased significantly (p Ë‚ .05). CONCLUSIONS: The results of this study illustrate that the presence of both PCOS and hypothyroidism alters the situation more than just PCOS. They also indicate that this situation is associated with imbalanced oxidative/antioxidative status.

Melatonin as a complementary and prophylactic agent against COVID-19 in high-risk populations: A narrative review of recent findings from clinical and preclinical studies.

The coronavirus disease 2019 (COVID-19) pandemic has been going on around the world for more than a year and has cost a lot, as well as affected the quality of life of many. The psychological stress like delirium and sleep disturbances caused by the COVID-19 has affected many people in direct or indirect way by the disease. Insomnia and sleep deprivation have a negative effect on the immune system as well as disorders of the hormonal system, including the production and secretion of melatonin, known as the sleep hormone. Melatonin is a known anti-inflammatory and antioxidant agent in addition to its role in regulating circadian rhythms. In this review, we investigated the relationship between the effect of psychological stress caused by COVID-19 on patients, their families, health care workers, and occupations as well as how melatonin might act as a prophylactic agent with sedative effects and sleep enhancement potential. Search terms "melatonin" and "COVID-19" were manually searched on PubMed or other electronic database and relevant articles were included. Based on the review of scholarly articles, it can be inferred that melatonin, as an endogenous hormone controlling and regulating sleep and wakefulness in various researches, has a good potential due to its antioxidant and anti-inflammatory with minimal side effects. These beneficial effects highlight the impact of melatonin as an adjuvant and a potential alternative for the better management of SARS-CoV-2 infection in high-risk populations.

Preventive Effects of Sinigrin Against the Memory Deterioration in the Pentylenetetrazole-Kindled Male Wistar Rats: Possible Modulation of NLRP3 Pathway.

Mainly found in brussels sprouts, broccoli, and black mustard seeds, sinigrin (2-propenyl glucosinolate) has enjoyed some attention currently for its effects on health and disease prevention. The present research design is aimed at investigating the effects of sinigrin on inflammation, oxidative stress (OS) and memory. Randomly, six groups of male Wistar rats were categorized into the control and experimental groups. The experimental groups were treated with sinigrin (10 and 20 mg/kg, orally). The control positive group was given the pentylenetetrazole (PTZ) treatment and the control negative one was given normal saline. All groups were kindled by the sub-threshold dose (35 mg/kg, i.p.) of PTZ for 12 times in one month. When the kindling procedure was done, the seizure behaviors and the behavioral function were evaluated. For cognitive parameters, the shuttle box test was employed. When the experiment was terminated, the rats were euthanized and their blood serum as well as brain samples were isolated for respective measuring of OS and gene expression parameters. The treatment with sinigrin significantly delayed the appearance of the seizure symptoms in comparison to that of the PTZ group. It also significantly increased the memory parameters like retention latency and the total time having been spent in the light compartment in the epileptic rats. In addition, sinigrin increased the superoxide dismutase and catalase levels. Treatment with sinigrin suppressed the Il1b and Nlrp3 gene expression at hippocampal level. In sum, sinigrin prevents inflammation, OS and memory impairment against the PTZ-kindling epilepsy in rats.

Treatment with human umbilical cord blood serum in a gentamicin-induced nephrotoxicity model in rats.

Sold under the brand name of Garamycin, gentamicin (GM) is an antibiotic in the category of aminoglycoside, that although does have many antibacterial properties, owing to several side effects, its consumption is confined. The current study is aimed at gauging the protective influences of human umbilical cord blood serum (hUCBS) on nephrotoxicity which is induced by GM. In this regard, in the present experimental design, twenty-eight male Wistar rats with the weights of 220 ± 20 g were categorized randomly into 4 groups of seven. The groups included GM (100 mg/kg), control as well as hUCBS at doses of one and two percent together with GM (100 mg/kg) for ten days in an intraperitoneal manner. Blood sampling was collected from the heart directly 24 h after the final injection for obtaining blood serum; the parameters of C-reactive protein (CRP), total oxidant status (TOS), interleukin (IL)-6, lactate dehydrogenase (LDH), total antioxidant capacity (TAC), creatinine (Cr), blood urea nitrogen (BUN), blood serum glutathione (GSH) were gauged in blood serum samples to evaluate renal function. Moreover, for histology, an examination of kidney tissue was performed. In comparison to those of the GM group, in the treatment group, hUCBS significantly decreased the levels of BUN, Cr, LDH, TOS, IL-6, and the CRP levels, and significantly increased the TAC and GSH levels. It was revealed that the treatment of the animals with hUCBS culminates in the reduction of GM' toxic impacts on the kidney.

NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement.

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1ß in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1ß, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1ß cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

Rapamycin alleviates memory deficit against pentylenetetrazole-induced neural toxicity in Wistar male rats.

Numerous studies have reported that epilepsy causes memory deficits. The present study was aimed at studying the effect of rapamycin against the memory deficiency of the pentylenetetrazole (PTZ)-kindled animal model of epilepsy. In the present experiment, we randomly chose thirty male rats from the species of Wistar and categorized them in groups of control and experiment (6 for each group). The groups of experiment received the injection of rapamycin (0.5, 1 and 2 mg/kg) intraperitoneally (i.p.) and the group of control received normal saline (0.9%) treatment. Through the PTZ's sub-threshold dose (35 mg kg-1, i.p.), all groups were kindled 12 times. Passive avoidance test (PAT) was used for gauging the memory function and the seizure behaviors after the kindling procedure. The rodents were sacrificed at the end of the trial and their brains were scooped for measuring the expression of Gabra1 and Pras40 genes. Statistical analysis unveiled that rapamycin delayed the kindling development and the onset of seizures which are tonic-clonic. Moreover, the administration of rapamycin significantly prevented memory dysfunction in epileptic rats. Finally, it was shown that rapamycin resulted in an increase in the expression levels of Gabra1 and Pras40 genes at the brain tissues. The current research design indicated that rapamycin has beneficial effects for the prevention of memory impairment against PTZ-kindling epilepsy in rats. Such promising outcomes could be attributed to its impact on the Gabra1 and Pras40 genes.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Rapamycin attenuates depression and anxiety-like behaviors through modulation of the NLRP3 pathway in pentylenetetrazole-kindled male Wistar rats.

BACKGROUND: There is cumulative evidence that shows the effect of epilepsy on behavioral conditions like anxiety and depression. OBJECTIVES: The effects of rapamycin on anxiety and depression caused by pentylenetetrazole (PTZ) in the rat and possible underlying mechanisms were evaluated. METHODS: Male Wistar rats were divided into experimental and control groups. The experimental groups were treated with intraperitoneal (i.p.) injection of 0.5, 1, and 2 mg/kg of rapamycin, while the control group received normal saline only. Kindling was induced by sub-threshold dose (35 mg/kg, i.p.) of PTZ for one month. When the kindling procedure was done, the seizure behaviors and the behavioral function were evaluated. For anxiety parameters, the elevated plus maze (EPM) was used. The forced swim test was employed to assess the antidepressant potential. At the end of the experiment, rats were euthanized and the blood serum and brain samples were isolated for respective measurement of oxidative stress and gene expression parameters. RESULTS: Rapamycin delayed the development of kindling and the onset time of seizures. Rapamycin administration reduced immobility time in the FST, exerting antidepressant-like activity. In the EPM test, rapamycin produced an anxiolytic-like effect. In addition, rapamycin increased the catalase and superoxide dismutase levels in the serum and significantly decreased the gene expression of I11b and Nlrp3 compared to the PTZ group. CONCLUSION: Our results showed that the inhibitory effect of mTOR inhibitor (rapamycin) on reactive oxygen species production during NLRP3 inflammasome activation could bring about behavioral alterations in anxiety and depression.

Vanillic acid attenuates amyloid ß1-40-induced long-term potentiation deficit in male rats: an in vivo investigation.

Objectives: Alzheimer disease (AD) is a neurodegenerative disorderliness that involves deductible progressive cognition function caused by amyloid-beta (Aß) peptide accumulation in the interstitial space. The increase of Aß stimulates all kinds of active oxygen and causes oxidative stress and apoptosis. In this investigation, we researched the neuroprotective impacts of vanillic acid (VA) on the Aß-induced (Aß1-40) long-term potentiation (LTP) of the hippocampus - a commonly probed synaptic plasticity model that happens at the same time as memory and learning - in the AD rats.Methods: Forty-five male Wistar rats were categorized into five groups (n = 8 rats/group, 200-220 g), and studied as control (standard diet), sham (vehicle), VA (50 mg/kg), Aß and Aß + VA (50 mg/kg) groups. In vivo electrophysiological recordings were implemented after the stereotaxic surgery to gauge the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the dentate gyrus of the hippocampus. By the stimulation at high-frequency of the perforate pathway, long-term potentiation (LTP) was induced. To assess the plasma levels of malondialdehyde (MDA) and total thiol group (TTG), blood samples were garnered.Results: In the Aß-injected rats, EPSP slope, and PS amplitude were significantly reduced after the induction of LTP. Thus, the findings demonstrate that VA decreases the impacts of Aß on LTP; also, the treatments through VA neuroprotective against the negative effects of Aß on the synaptic plasticity of the hippocampus can decrease the MDA levels and also increase the TTG levels significantly.Discussion: Therefore, based on this experiment on male rats, VA has neuroprotective effects and antioxidants benefits against the Aß-mediated inhibition of long-term potentiation.

Human umbilical cord blood serum attenuates gentamicin-induced liver toxicity by restoring peripheral oxidative damage and inflammation in rats.

Gentamicin (GM) is an aminoglycoside antibiotic that despite its antibacterial effects, its use is restricted due to numerous side effects. The umbilical cord serum contains various biomolecules that have protective impacts on the damaged tissues. The aim of this study was to gauge the protective effect of human umbilical cord blood serum (hUCBS) on GM-induced hepatotoxicity. In this experimental study, 28 male Wistar rats, weighing 220 ± 20 g, were randomly categorized into 4 groups including control, GM (100 mg/kg), hUCBS at doses of 1 and 2% along with GM (100 mg/kg) for 10 days, intraperitoneally. Twenty-four hours after the last injection, direct blood sampling was taken from the heart to obtain blood serum and liver enzymes, inflammatory cytokines and liver tissue were examined for histology. GM causes necrosis and inflammation in liver tissue. Liver enzyme and inflammatory cytokine levels were significantly increased in the GM group. Human umbilical cord blood serum significantly decreased liver enzyme and inflammatory cytokines levels in the experimental groups compared to the GM group. GM causes liver damage such as the inflammation and necrosis in liver tissue. Treating the animals with hUCBS reduced the toxic effects of GM in the liver.

Central injection of neuropeptide Y modulates sexual behavior in male rats: interaction with GnRH and kisspeptin/neurokinin B/dynorphin.

AIMS: A number of studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of hypothalamic-pituitary-gonadal (HPG) axis in the mammals. In addition, kisspeptin (encode by Kiss1 gene), neurokinin B (encode by Tac3 gene) and dynorphin (encode by Pdyn gene) (commonly known as KNDy secreting neurons) are a powerful upstream regulators of GnRH neuron in hypothalamus. MATERIALS AND METHODS: The present study aims to investigate the effects of the intracerebroventricular (icv) injection of NPY and BIBP3226 (NPY receptor antagonist (NPYRA)) on the male sexual behavioral. Additionally, in order to see whether NPY signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin, the gene expression of these peptides along with Gnrh1 gene in the hypothalamus were measured. RESULTS: The icv injection of NPY decreased the latencies and increase the frequencies of sexual parameters of the male rats in a significant way. In this line, NPYRA antagonized the stimulative effects of NPY. Moreover, data from real-time quantitative PCR indicated that injection of NPY significantly increased the gene expression of Gnrh1, Kiss1 and Tac3 and decrease the Pdyn while treatment with NPYRA controlled the modulative effects of NPY on these gene expression. CONCLUSIONS: In conclusion based on the results of this study, NPY can exert its impacts on the sexual behavior of male rats via modulation of the KNDy secreting neurons as an interneural pathway to GnRH neurons.