Methane-rich saline ameliorates depressive-like behaviors during chronic unpredictable mild stress (CUMS).

Depression, considered the most prevalent neuropsychiatric disorder, is multifactorial and complex. Oxidative stress and inflammation significantly contribute to its etiology. Conversely, methane, a novel therapeutic gas, has demonstrated efficacy in enhancing tissue resilience against ischemic injuries and inflammation. In this study, we investigated the effect of methane-rich saline (MRS) on depression using the chronic unpredictable mild stress (CUMS) model. Depressed rats received MRS treatment, and depression-like behaviors and cognitive function were assessed through sucrose preference, open field, forced swimming, and Morris water maze tests. Additionally, we measured serum corticosterone levels, antioxidant enzyme activity, hippocampal malondialdehyde (MDA), and TNFα levels, and investigated histological changes in the hippocampus. Our findings revealed that MRS significantly ameliorated Depressive-like behaviors and cognitive impairment. Furthermore, MRS administration regulated serum corticosterone levels and also MRS reduced hippocampal lipid peroxidation, TNFα, and hippocampus tissue damage. MRS likely exerts its effects by reducing oxidative stress and inflammatory factors and modulating the function of the hypothalamus-pituitary-adrenal (HPA) axis. These results demonstrate the protective effects of MRS on the hippocampus in CUMS animals.

Improved ovarian adiponectin system expression in polycystic ovary syndrome treated with exenatide.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility. This experimental study was conducted to elucidate the role of adiponectin signaling in rats with PCOS treated with exenatide. Twenty-eight adult female Wistar rats were divided into four groups of seven. The normal group did not receive any drug. The PCOS+vehicle (Veh) group received estradiol valerate to induce PCOS, then was divided into PCOS +E50 and PCOS+E100 groups and treated with 50 or 100 mg/kg doses of exenatide, respectively. The mRNA expression of adiponectin and adiponectin receptor 1 (Adipo-R1) was evaluated using a semi-quantitative real-time polymerase chain reaction. The results indicated that the level of adiponectin diminished in the PCOS rats while exenatide increased adiponectin expression at both doses. Adiponectin receptor mRNA levels were higher in the PCOS rats than in the normal rats (p<0.05). In addition, exenatide decreased the levels of Adipo-R1 expression. Taken together, our results showed that exenatide may improve PCOS characteristics in rats through the molecular regulation of adiponectin and its receptor.

Possible Impact of Human ß-defensin 1 on sperm motility in infertile men with abnormal sperm parameters.

Human ß-defensins and interleukins may be auxiliary in sperm maturation. This cross-sectional study aimed to evaluate the expression of Human ß-defensins 1 and 2, interleukins (ILs)- 10 and -18 genes in sperm, as well as seminal plasma levels of these two cytokines in subfertile men with different types of sperm abnormalities compared to those with normozoospermic men. Participants were separated into two experimental groups: the control group (n = 25) and the group with sperm abnormalities (SA) (n = 45). SA participants were further subdivided into the following groups with n = 15 individuals each: Teratozoospermia (T), Asthenoteratozoospermia (AT), and Oligoasthenoteratozoospermia (OAT) groups. The quantitative real-time polymerase chain reaction was used to quantify the mRNA levels of hBDs 1 and 2, IL-10, and IL-18 in sperm. The seminal plasma concentrations of IL-10 and IL-18 were measured by using the enzyme-linked immunosorbent assay technique. The mRNA expression of hBD-1 and IL-10 showed a significant decrease in the OAT compared to the controls (P < 0.0001 and P = 0.02, respectively). The lowest seminal plasma concentration of IL-10 belonged to the OAT (P = 0.04). ROC curve analysis showed a sensitivity, specificity, and cutoff value of 82.35%, 86.67%, and 0.63 for hBD-1 levels, respectively. A positive and significant correlation was found between hBD-1 expression and sperm motility and IL-10 expression rate and normal sperm morphology.Therefore, hBD-1 could be considered as the alternative biomaterial to pre-treatments of infertile men with abnormal sperm parameters, specifically OAT men, which led to improving the assisted reproduction success rate.

Sperm Selection Using Zona Pellucida-Binding Enhanced Embryo Morphokinetic and Clinical Outcomes in ICSI: A Sibling Oocytes Study.

The objective was to investigate the embryo morphokinitics using a time-lapse monitoring (TLM) system and assessment of clinical outcomes following intracytoplasmic sperm injection (ICSI) with zona pellucida (ZP)-bound sperm selection and conventional methods. A total of 371 metaphase II (MII) oocytes from 50 ICSI cycles were studied. Sibling oocytes were randomly divided into control (n = 199) and ZP-bound group (n = 172). All resulting zygotes were cultured and monitored in the TLM system up to Day 3 after ICSI. Fertilization rate, early embryo development, and clinical outcomes were evaluated. No significant differences were found in fertilization rate, time-lapse qualitative and quantitative measures, pronuclear fading time (PNF) t2, t3, t4, t5, t6, and t7 (times of cleavage to 2, 3, 4, 5, 6, and 7 cells), respectively. However, the t8 (time of cleavage to eight cells) and cc3 (duration of third cell cycle) revealed a significant difference between control and ZP-bound groups (p < .05). A significant difference between the two groups (p < .05) in the rates of Grade A embryos (according to Basile algorithm), chemical pregnancy, clinical pregnancy, and implantation was observed. Sperm selection using biological materials, such as ZP, improved both embryo quality and pregnancy outcomes, despite not affecting the early embryo development and morphokinetic parameters up to t8. This prospective randomized sibling oocyte trial was registered in October 2020 to January 2022 (IRCT20200705048021N1).

Effect of vitamin C on histomorphometric changes of testis, epididymis, prostate, and seminal vesicle induced by acrylamide in rat.

Acrylamide (ACR) has adverse effects on the rat testis. This study aimed to assess the impact of ACR and vit C exposure on reproductive organs in rats. In this experimental study, 32 adult male rats were used. The animals were divided into 4 groups (n = 8): (1) control group, (2) ACR (10 mg/kg) group, (3) vit C (200 mg/kg), (4) ACR (10 mg/kg) + vit C (200 mg/kg) daily for 5 weeks by gavage. After the administration period, testis, prostate, seminal vesicle, and epididymis of animals are removed; after preparing tissue sections, the structural changes of the tissues are examined by stereology. Data were analyzed using one-way ANOVA followed by the Tukey test in SPSS software. A value of p ≤ 0.05 was considered significant. The testis weight, volume (mm3), and the mean Johnsen score showed a significant decrease in comparison with the control group and vit C-treated group. These parameters were increased in ACR + vit C group. The number of spermatogonia, spermatocyte, spermatid, and Sertoli and Leydig cells in ACR-treated group showed a significant decrease in comparison with the control and vit C-treated groups. The number of these cells was increased in the ACR + vit C group. Epithelium height and folding of prostate and seminal vesicle in the ACR-treated group were decreased. Epithelium lost its integrity. In the ACR + vit C group, histopathological changes were decreased. Seminal vesicle of ACR + vit C-treated group showed mild degeneration and rupture in epithelium integrity. The epididymis of ACR + vit C group also showed mild degeneration and rupture in epithelium integrity.

Antidepressant-like effect of endogenous SO2 on depression caused by chronic unpredictable mild stress.

Sulfur dioxide (SO2) is a toxic gas with harmful effects on various organs. However, recent studies have confirmed the protective effect of SO2 on ischemic heart disease, atherosclerosis, and lung infections. Therefore, the present study was designed to investigate the effect of endogenous SO2 on depression. The chronic unpredictable mild stress (CUMS) model was performed to cause depression. Depression-like behaviors in animals were determined using an open-field test, forced swimming test, and sucrose consumption. Animal spatial learning and memory were also assessed using the Morris water maze. Besides, the oxidative status of the hippocampus and serum corticosterone level were evaluated. A reduction in the tendency to consume sucrose, mobility, and curiosity, as well as learning and memory disorders were observed in CUMS animals. Depressed animals treated with SO2 revealed a significant improvement in behavioral and cognitive functions. SO2 also reduced neuronal damage and lipid peroxidation of the hippocampus and serum corticosterone level in the CUMS group. Various shreds of evidence support a mutual relationship between inflammation and depression; also, growing studies show the role of oxidative stress in the pathogenesis of mood-related disorders such as depression. This study indicated that increased hippocampal malondialdehyde (MDA) and serum corticosterone levels can be due to the existence of oxidative stress and possible activation of inflammatory processes. SO2 donors diminished MDA and corticosterone levels in depressed animals. According to the study results, SO2 may be able to reduce tissue damage and eventually behavioral disorders caused by depression by lowering oxidative stress and inflammation.

Ferulic Acid Ameliorates Cell Injuries, Cognitive and Motor Impairments in Cuprizone-Induced Demyelination Model of Multiple Sclerosis.

OBJECTIVE: Ferulic acid (FA) is a phenolic compound that exhibits neuroprotective effects in the central nervous system (CNS). This study was conducted to evaluate the potential effects of FA on the cognitive and motor impairments in the cuprizone-induced demyelination model of multiple sclerosis (MS). MATERIALS AND METHODS: In this experimental study, demyelination was induced in mice by feeding them with chow containing cuprizone (CPZ) 0.2% for 6 weeks. Mice in the control group received normal chow. Mice in the CPZ+Veh, CPZ+FA10, and CPZ+FA100 groups received saline, and FA at a dose of 0, 10, or 100 mg/kg (intraperitoneal, I.P., daily) respectively. After cognitive and motor assessments, under anaesthesia, animal brains were removed for evaluating the histological, apoptosis, and molecular changes. RESULTS: The results showed that FA increased freezing behaviour in contextual (P<0.05) and cued freezing tests (P<0.05). FA also reduced the random arm entrance (P<0.01) and increased spontaneous alternations into the arms of Y-maze compared to the CPZ+Veh group (P<0.05). Time on the rotarod was improved in rats that received both doses of FA (P<0.01). Demyelination, apoptosis, and relative mRNA expression of p53 were lower in the FA-treated groups relative to the CPZ+Veh group (P<0.01). In addition, FA increased mRNA expression of brain-derived neurotrophic factor (Bdnf), Olig2, and Mbp (P<0.05) but decreased GFAP mRNA expression compared to the CPZ+Veh group (P<0.01). CONCLUSION: The results of this study showed that FA plays a significant neuroprotective role in CPZ models of demyelination by reducing neuronal apoptosis and improving oligodendrocytes (OLs) growth and differentiation.

The G-Protein-Coupled Estrogen Receptor Agonist Prevents Cardiac Lipid Accumulation by Stimulating Cardiac Peroxisome Proliferator-Activated Receptor α: A Preclinical Study in Ovariectomized-Diabetic Rat Model.

Background: Type 2 diabetes mellitus (T2DM) is associated with cardiometabolic changes, and menopause exacerbates these conditions, leading to a greater risk of cardiovascular diseases (CVDs). The G protein-coupled estrogen receptor (GPER), which mediates the rapid effects of estrogen, has beneficial cardiac effects in both T2DM and menopause, but its mechanism of action is not well understood. Objectives: This study aimed to determine whether G1 as a selective GPER-agonist has beneficial effects on cardiac lipid metabolism in ovariectomized rats with T2DM. Methods: Female Wistar rats were divided into 5 groups (n = 7 in each group): Sham-control (Sh-Ctl), T2DM, ovariectomized-T2DM (OVX-T2DM), OVX-T2DM-G1 (GPER-agonist), and OVX-T2DM-vehicle (OVX-T2DM-Veh). After stabilization of T2DM, G1 (200 µg/Kg) was administrated for 6 weeks. Then, the levels of free fatty acids (FFAs), CD36, peroxisome proliferator-activated receptor α (PPARα), and lipid accumulation in the cardiac tissue were determined. Results: Compared with the Sh-Ctl group, cardiac FFAs (P < 0.001), CD36 (P < 0.05), and lipid accumulation (P < 0.001) increased, and cardiac PPARα (P < 0.01) decreased in T2DM animals; ovariectomy intensified these changes. Also, cardiac FFAs, PPARα, and lipid accumulation (P < 0.05) significantly decreased in the OVX-T2DM-G1 group compared to the OVX-T2DM-Veh group. However, cardiac CD36 levels did not change. Conclusions: G1 as a selective GPER-agonist affects lipid metabolism in T2DM animals. It also plays a vital role in improving cardiac metabolism during postmenopausal diabetic conditions.

Mesenchymal stem cells-derived exosomes as a promising new approach for the treatment of infertility caused by polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic and most common endocrine disorder that its prevalence, depending on different methods of evaluating PCOS traits, varies from 4% to 21%. Chronic low-grade inflammation and irregular apoptosis of granulosa cells play a crucial role in the pathogenesis of PCOS infertility. Mesenchymal stem cells (MSCs)-derived exosomes and extracellular vesicles (EVs) are lipid bilayer complexes that act as a means of intercellular transferring of proteins, lipids, DNA and different types of RNAs. It seems that this nanoparticles have therapeutic effects on the PCOS ovary such as regulating immunity response, anti-inflammatory (local and systemic) and suppress of granulosa cells (GCs) apoptosis. Although there are few studies demonstrating the effects of exosomes on PCOS and their exact mechanisms is still unknown, in the present study we reviewed the available studies of the functions of MSC-derived exosome, EVs and secretome on apoptosis of granulosa cells and inflammation in the ovary. Therefore, the novel cell-free therapeutic approaches for PCOS were suggested in this study.

Use of zona pellucida-bound spermatozoa as a natural selection in improvement of ICSI outcomes: A systematic review and meta-analysis.

Zona pellucida (ZP)-bound spermatozoa have normal morphology and motility and can enhance the ICSI outcomes. Selection of zona pellucida-bound spermatozoa is recently considered to find functional spermatozoa for ICSI. This study reviewed the efficacy of ZP-bound sperm selection on the ICSI outcomes includes fertilisation rate, embryo quality, embryo transfer rate and clinical pregnancy rate. The databases searched include PubMed, Scopus and Cochrane databases up to January 2019. All research reports with full text and in English language that addressing the relation between ZP-sperm selection and ICSI outcomes were included. Fifty studies were suitable after screening of the 845 identified articles. After exclusions, five of these studies were included. Meta-analytic pooling of data indicated no association between the ICSI outcomes and ZP-bound sperm selection except a marginal effect on implantation rate. Eliminating one study indicated that ZP-bound sperm selection technique improves embryo quality, implantation rate and clinical pregnancy rate. This study revealed that ZP-bound sperm selection produces only a slight improvement in implantation rate. However, further studies with a large number of couples must be done to clarify the potential beneficial effect of ZP-bound spermatozoa on ICSI outcomes.

Chronic niacin administration ameliorates ovulation, histological changes in the ovary and adiponectin concentrations in a rat model of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common ovarian diseases among women of reproductive age. The reproductive and metabolic traits of PCOS are underpinned by adipocyte dysfunction, especially diminished adiponectin secretion. Based on evidence that niacin stimulates adiponectin secretion, this study evaluated the effects of niacin on adiponectin concentrations and reproductive traits in a rat model of PCOS. PCOS was induced by single injection of 4mg kg-1 oestradiol valerate (i.m.), and PCOS groups were administered orally with saline or niacin (10 or 25mg kg-1) daily for 30 days after PCOS induction. The control group received 0.2mL sesame oil (i.m.) only. At the end of the experimental period, serum samples and ovaries were collected for adiponectin, histological and molecular analyses. Niacin reduced the bodyweight gain and increased ovary weights in PCOS rats. Niacin also increased the number of normal antral follicles and corpora lutea while reducing the number of cystic follicles and the thickness of theca interna. Moreover, niacin significantly increased serum adiponectin concentration and the gene expression of adiponectin and its type 1 receptor. In conclusion, this study indicates that niacin reduces cystic follicles and improves ovulation in PCOS rats. Adiponectin signalling may have contributed, in part, to the beneficial effects.

Safety assessment of genetically modified rice expressing Cry1Ab protein in Sprague-Dawley rats.

Rice is considered one of the most important staple food crops. Genetically modified (GM) Bt rice, harbored cry1Ab gene expressing the insect-resistance protein has been developed to resistance to the insects. In this study, we assessed the safety of the GM Bt rice on Sprague-Dawley rats for 90 days. Totally, 120 rats in both sexes were used for three different diets, including 50% GM Bt rice, feeding with 50% rice, and standard feeding. Each 40 SD rats including 20 males and 20 females were considered as each diet. The clinical variables such as body weight and food consumption were measured and a range of clinical tests was examined, including hematology, serum chemistry parameters, urinalysis profile, thyroid, and sex hormone levels. Pathological assessments were also done. The results showed that the mean weekly feed utilization (%) had no significant difference among the studied groups. Also, blood biochemistry, hematological parameters, urine analysis, and hormonal levels had no significant differences among the groups. However, alanine aminotransferase was less in males versus female feeding with GM Bt rice. No histopathological changes were observed among the groups. In conclusion, this study demonstrated that GM Bt rice had no obvious adverse effects on rats' health.

Mesenchymal Stem-Cell Derived Exosome Therapy as a Potential Future Approach for Treatment of Male Infertility Caused by Chlamydia Infection.

Some microbial sexually transmitted infections (STIs) have adverse effects on the reproductive tract, sperm function, and male fertility. Given that STIs are often asymptomatic and cause major complications such as urogenital inflammation, fibrosis, and scarring, optimal treatments should be performed to prevent the noxious effect of STIs on male fertility. Among STIs, Chlamydia trachomatis is the most common asymptomatic preventable bacterial STI. C. trachomatis can affect both sperm and the male reproductive tract. Recently, mesenchymal stem cells (MSCs) derived exosomes have been considered as a new therapeutic medicine due to their immunomodulatory, anti-inflammatory, anti-oxidant, and regenerative effects without consequences through the stem cell transplantation based therapies. Inflammation of the genital tract and sperm dysfunction are the consequences of the microbial infections, especially Chlamydia trachomatis. Exosome therapy as a noninvasive approach has shown promising results on the ability to regenerate the damaged sperm and treating asthenozoospermia. Recent experimental methods may be helpful in the novel treatments of male infertility. Thus, it is demonstrated that exosomes play an important role in preventing the consequences of infection, and thereby preventing inflammation, reducing cell damage, inhibiting fibrogenesis, and reducing scar formation. This review aimed to overview the studies about the potential therapeutic roles of MSCs-derived exosomes on sperm abnormalities and male infertility caused by STIs.

Effect of myricetin on the gene expressions of NOX3, TGF-ß1, prestin, and HSP-70 and anti-oxidant activity in the cochlea of noise-exposed rats.

OBJECTIVES: Noise-induced hearing loss is one of the most common occupational diseases in industrialized countries and can be affected by various environmental and genetic factors. This study was designed to examine the effect of myricetin in preventing this disorder. MATERIALS AND METHODS: Twenty-one Wistar rats were randomly divided into five groups: Non-exposed, noise exposure only, noise exposure with vehicle, noise exposure with myricetin 5 mg/Kg, and noise exposure with myricetin 10 mg/kg. All animals were sacrificed after last noise exposure. The left cochlea was dissected from each rat. It was used for mRNA expression analysis (NOX3, TGF-ß1, prestin, and HSP-70). Blood samples were collected to assess superoxide dismutase (SOD) activity, 1, 1 diphenyl picrylhydrazyl (DPPH), and malondialdehyde (MDA) measurements. RESULTS: Real time-PCR assay revealed that noise decreased NOX3 and increased TGF-ß1, prestin, and HSP-70 gene expressions. Administration of myricetin at the dose of 5 mg/kg, but not at 10 mg/kg, significantly reversed these changes. Noise also increased MDA levels and decreased SOD and DPPH scavenging activities. Myricetin at the doses of 5 and 10 mg/kg also reversed these changes. CONCLUSION: The findings of this study showed that myricetin at the dose of 5 mg/Kg was able to reverse noise-induced abnormalities in gene expression and oxidant/anti-oxidant balance. It is a possibility that myricetin via enhancement of anti-oxidant activity induced these effects.

17ß-Estradiol improves insulin signalling and insulin resistance in the aged female hearts: Role of inflammatory and anti-inflammatory cytokines.

Aging effects in energy balance in all tissues and organs, including the cardiovascular. The risk of cardiovascular disease is drastically higher in postmenopausal women than in premenopausal women. Estrogen plays an important role in the cardiac function and body's metabolism. The aim of this study was to determine whether 17ß-estradiol (E2) has beneficial effects on insulin resistance and some key stages of the insulin signalling pathway in the aged hearts. Young and aged female Wistar rats were ovariectomized and were randomly divided into three groups: young (YS) and aged (AS) sham, young (YV) and aged (AV) vehicle, and young (YE2) and aged (AE2) E2 treatment groups. E2 (1 mg/kg) was administrated every four days for four weeks. Results showed that ovariectomy increased fasting blood glucose, insulin, and HOMAIR in young, while none of these parameters was affected in aged animals. On the other hand, aging itself increased these variables. Furthermore, E2 therapy alleviated these changes in both young and aged animals. Moreover, aging also decreased the p-IRS1, p-Akt level, and translocation of GLUT4 to the plasma membrane. E2 reduced the negative impact of menopause and aging on insulin sensitivity by favoring increase in the level of IL-10 and decrease in the levels of TNF-α and IL-1ß. Our results indicated that the heart response to E2 depended on age, and E2 increased insulin sensitivity in the heart of both young and aged animals by altering inflammatory conditions. Determining the exact mechanism of this action is suggested in future studies.

Resveratrol suppresses interleukin-6 expression through activation of sirtuin 1 in hypertrophied H9c2 cardiomyoblasts.

Inflammatory cytokine, interleukin-6 (IL-6), plays an important role in the pathogenesis of cardiac hypertrophy. Recent studies have documented that resveratrol exhibits cardioprotective effects. The present study attempts to explore whether resveratrol suppreses IL-6 in hypertrophied H9c2 cardiomyoblasts through histone deacetylase, sirtuin 1 (SIRT1). To induce hypertrophy, the cells were incubated with angiotensin II (Ang II). Treatment groups were treated with different doses (1, 10, 25, 50, 75, and 100 µM) of resveratrol (R). Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell size was determined using crystal violet staining. Gene expression was assessed by real-time polymerase chain reaction technique. Enzyme-linked immunosorbent assay was used to measure IL-6 concentration. The results showed that cell area and ANP messenger RNA (mRNA) levels decreased significantly in R25+Ang, R50+Ang, and R100+Ang groups, as compared with Ang group. Therefore, 10, 20, 30, 40, and 50 µM of resveratrol were used to to evaluate its anti-inflammatory effects. The results revealed that Ang II upregulated IL-6 at both mRNA and protein levels (p < .001 vs. normal) and resveratrol (50 µM) decreased IL-6 mRNA (p < .01) and protein (p < .05) significantly in comparison to Ang group. However, in groups in which the cells were pretreated with SIRT1 inhibitor, EX-527, the response of resveratrol was partially reversed. Transcription levels of IL-6 receptor components (gp130 and gp80) did not change significantly among the experimental groups. The current data suggests that resveratrol protects H9c2 cells against Ang II-induced hypertrophy by suppression of IL-6 through SIRT1 activation.

Effect of endogenous sulfur dioxide on spatial learning and memory and hippocampal damages in the experimental model of chronic cerebral hypoperfusion.

Background The vascular changes due to cerebrovascular damage, especially on the capillaries, play a vital role in causing vascular dementia. Increasing oxidative stress can lead to tissue damage while reducing brain blood flow. The use of factors reducing the oxidative stress level can decrease the brain damages. Sulfur dioxide (SO2) is one of the most important air pollutants that lead to the development of severe brain damage in large quantities. However, studies have recently confirmed the protective effect of SO2 in cardiac ischemic injury, atherosclerosis and pulmonary infections. Methods The permanent bilateral common carotid artery occlusion (BCAO) method was used to induce chronic cerebral hypoperfusion (CCH). Two treatment groups of SO2 were studied. The animal cognitive performance was evaluated using the Morris water maze. Hippocampal tissue damage was examined after 2 months of BCAO. In the biochemical analysis, the activity of catalase and lipid peroxidation of the hippocampus was studied. Results Neuronal damage in hippocampus, as well as cognitive impairment in ischemia groups treated with SO2 showed a significant improvement. Catalase activity was also significantly increased in the hippocampus of treated groups. Conclusions According to the results, SO2 is likely to be effective in reducing the CCH-caused damages by increasing the antioxidant capacity of the hippocampus.

Carvacrol suppresses learning and memory dysfunction and hippocampal damages caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a common phenomenon in many neurological diseases such as vascular dementia and Alzheimer's disease. Several drugs have been investigated to prevent and treat the CCH. The carvacrol (CAR) has been shown to have beneficial effects on various neurodegenerative and neuropsychiatric disorders. Accordingly, the present study was designed to evaluate the effect of CAR on neuronal damages in hippocampus in a well-defined model for CCH. Forty-eight male Wistar rats were equally divided into four groups of sham (A), CCH (B), CCH+ CAR 25, and 50 mg/kg/daily (C and D). The animals were subjected to permanent bilateral occlusion of the carotid arteries (2-vessel occlusion, 2VO) to induce CCH model. Cognitive function was evaluated by Morris water maze test. Morphological changes of hippocampus were assessed using Nissl staining. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, catalase (CAT) and superoxide dismutase (SOD) activities and lipid peroxidation levels were measured using biochemical analysis. CAR significantly improved the spatial learning and memory deficits assessed using the Morris water maze test. CAR also significantly attenuated neuronal necrosis as well as malondialdehyde (MDA) and elevated the levels of SOD and CAT activity in the hippocampus. The results indicate that CAR produces significant neuroprotective effects on neuronal damages induced by CCH. Protective effect of CAR may be mediated by antioxidative effect of this drug.

Effect of Myricetin on the Prevention of Noise-Induced Hearing Loss-An Animal Model.

INTRODUCTION: Exposure to hazardous noise induces one of the forms of acquired and preventable hearing loss that is noise-induced hearing loss (NIHL). Considering oxidative stress as the main mechanism of NIHL, it is possible that myricetin can protect NIHL by its antioxidant effect. Therefore, the present study aimed to investigate the preventive effect of myricetin on NIHL. MATERIALS AND METHODS: A total of 21 Wistar rats were randomly divided into five groups, namely (1) noise exposure only as control group, (2) noise exposure with the vehicle of myricetin as solvent group, (3) noise exposure with myricetin 5 mg/kg as myricetin 5 mg group, (4) noise exposure with myricetin 10 mg/kg as myricetin 10 mg group, (5) and non-exposed as sham group. The hearing status of each animal was assessed by Distortion Product Otoacoustic Emissions. RESULTS: The levels of response amplitude decreased after the exposure to noise in all groups and returned to a higher level after 14 days of noise abstinence at most frequencies; however, the difference was not significant in the myricetin-receiving or control groups. CONCLUSION: The results of this study showed that two doses of myricetin (5 and 10 mg/kg) administered intraperitoneally could not significantly decrease transient or permanent threshold shifts in rats exposed to loud noise.

The effect of intermittent fasting diet on the hippocampus of adult male mouse after inducing demyelination by ethidium bromide injection / Efecto de la dieta de ayuno intermitente en el hipocampo de ratón macho adulto después de inducir la desmielinización por inyección de bromuro de etidio

Intermittent fasting diet (IF) as a restrictive regimen prevents neural degeneration and stimulates overexpression of various neurotropic factors in the hippocampus of animal models. This study evaluates the potential effect of the IF in the prevention of learning and memory dysfunction and improving the alterations in the number and volume of neurons in an ethidium bromide (EB) induced mouse model of demyelination.Mice were randomly assigned into N group (Normal Diet and normal saline injection), F group (IF and normal saline injection), EBN group (Normal Diet and EB injection), EBF group (IF and EB injection). The hidden platform test was carried out based on path length, escape latency and swim speeds of mice. Stereological studies were determined by the Cavalieri and the Optical Dissector technique. Maintenance of mice on the IF results in significantly decreased the body weight and biochemical parameters, increased total number of neurons and volume of the hippocampus, and improved learning and memory parameters of adult male mice. However, IF in EBF group did not show as excellently as F group. The EBF group displayed significantly spatial memory improvement than that in EBN group. There were no statistically significant differences between EBF and EBN groups in stereological and learning parameters, though the EBF group displayed faster escape latencies, and swam faster and shorter path lengths than the EBN group in these parameters. Therefore as a conclusion, The IF fairly improved some adverse effects of EB in experimental demyelination models.

La dieta de ayuno intermitente (AI) como régimen restrictivo, previene la degeneración neural y la estimación de la presencia de diversos factores neurotrópicos en el hipocampo de modelos animales. Este estudio evalúa el efecto potencial de la AI en la prevención del aprendizaje y la disfunción de la memoria y mejora las alteraciones en el número y el volumen de las neuronas en un modelo de desmielinización, en ratón, inducido con bromuro de etidio (BE). Los ratones se asignaron al azar en el grupo N (dieta normal e inyección salina normal), Grupo A (AI e inyección salina normal), Grupo BEN (dieta normal e inyección BE), Grupo EBF (inyección AI y BE). La prueba de la plataforma oculta se llevó a cabo en función de la longitud del trayecto, la latencia de escape y la velocidad de nado de los ratones. Los estudios estereológicos fueron determinados por la técnica de Cavalieri y la técnica del disector óptico. En el grupo AI disminuyeron significativamente el peso corporal de los ratones, los parámetros bioquímicos, el número total de neuronas y el volumen del hipocampo, y los parámetros de aprendizaje y la memoria de los ratones machos adultos. Sin embargo, el grupo AI en BEF no se mostró tan bien como el grupo A. El grupo EBF mostró una mejora en la memoria espacial significativamente mayor que la del grupo BEN. No hubo diferencias estadísticamente significativas entre los grupos A, BE y BEN en los parámetros estereológicos y de aprendizaje, aunque el grupo EBF mostró latencias de escape más rápidas, y nado en las rutas más rápidas y más cortas que el grupo BEN en estos parámetros. Por lo tanto, como conclusión, el grupo AI mejoró bastante algunos efectos adversos de la BE en los modelos de desmielinización experimental.