Effect of berberine on the hippocampal structure, biochemical factors, memory, and blood-brain barrier in rat model of transient global cerebral ischemia.

Global cerebral ischemia (GCI) results in damage to the neurons and leads to cognitive impairments. Berberine (BBR) is known for its neuroprotective qualities. This study aimed to investigate the effects of BBR on memory, Blood-brain barrier (BBB) permeability, biochemical factors, and neuronal structure. Sixty-three adult male Wistar rats were divided randomly into Sham (21), GCI (21), and GCI + BBR (21) groups. The GCI + BBR group received 50 mg/kg of BBR for 7 days before and 6 h after 20 min of GCI induction. After 24 h, assessments included hippocampal neuronal structure, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPX) levels, memory performance, and BBB permeability. The GCI + BBR group reduced volume loss in the CA1 and its sublayers (oriens, pyramidal, and radiatum) compared to the GCI group (p < 0.0001, p < 0.001, p < 0.01 and p < 0.001, respectively). Additionally, the GCI + BBR group showed higher pyramidal neuron density (p < 0.0001) and number (p < 0.0001) compared to the GCI group. BBR also decreased MDA levels (p < 0.0001) and increased CAT activity (p < 0.0001) in the GCI + BBR group compared to the GCI group, with GPX and SOD activity approaching Sham levels (p < 0.0001, both). BBR demonstrated significant improvements in short and long-term memory compared to the GCI group (p < 0.01, p < 0.0001, respectively). Furthermore, BBB permeability in the GCI + BBR group was significantly reduced compared to the GCI group (p < 0.0001). These findings demonstrated BBR's potential to protect the neurons in the CA1 and BBB structures, enhance antioxidant activity, and alleviate GCI-induced memory impairments.

Resveratrol Confers Protection Against Ischemia/Reperfusion Injury by Increase of Angiotensin (1-7) Expression in a Rat Model of Myocardial Hypertrophy.

ABSTRACT: Left ventricular hypertrophy (LVH) makes the heart vulnerable to ischemia/reperfusion (IR) injury. Angiotensin (Ang) (1-7) is recognized as a cardioprotective peptide. We investigated the effect of polyphenol resveratrol on myocardial IR injury after hypertrophy and examined cardiac content of Ang (1-7) and transcription of its receptor (MasR). Rats were divided into sham-operated, LVH, IR, LVH + IR, and resveratrol + LVH + IR groups. Myocardial hypertrophy and IR models were created by abdominal aortic banding and left coronary artery occlusion, respectively. To evaluate the electrocardiogram parameters and incidence of arrhythmias, electrocardiogram was recorded by subcutaneous leads (lead II). Blood pressure was measured through the left carotid artery. Infarct size was determined by the triphenyl tetrazolium chloride staining. The Ang (1-7) level was evaluated by immunohistochemistry. The Mas receptor mRNA level was assessed by the real-time real time reverse transcription polymerase chain reaction technique. QT-interval duration, infarct size, and incidence of ischemia-induced arrhythmia were significantly higher in the LVH + IR group. However, in the resveratrol-treated group, these parameters were decreased significantly. The cardiac level of Ang (1-7) was decreased in untreated hypertrophied hearts (LVH and LVH + IR groups). Pretreatment with resveratrol normalized the cardiac level of Ang (1-7). The mRNA level of Mas receptor was increased in all of hypertrophied hearts in the presence or absence of resveratrol. Resveratrol can decrease IR injury in rats with LVH. The anti-ischemic effect of resveratrol may be related to the enhancement of Ang (1-7)/MasR axis.

Altered expression patterns of complement factor H and miR-146a genes in acute-chronic phases in experimental autoimmune encephalomyelitis mouse.

Considerable advances have been made in identification of the involvement of immune modulators in diseases. There is growing evidence on the role of complement pathway in pathogenesis and course of multiple sclerosis (MS). Moreover, it has been recognized that microRNAs (miRNAs) play an essential role in modulation and development of immune response in the central nervous system. We aimed to investigate the expression profile of complement factor H (CFH) and miR-146a genes in experimental autoimmune encephalomyelitis (EAE) mouse model of MS to detect the possible roles of CFH and miR-146a as biomarkers of MS disease stats. Expression of CFH and miR-146a genes in liver and brain tissues of EAE mice was measured in acute and chronic phases of disease compared to matched controls using real-time polymerase chain reaction. In the liver, increased expression of CFH gene was observed in the chronic phase compared to the acute phase. However, no significant difference was observed between acute and chronic phase mice with normal mice, while miR-146a expression was significantly decreased in livers of EAE mice in chronic group compared to acute and control groups. The expression of CFH gene in brain had a significant decrease in acute and chronic phases compared to healthy mice. Taken together, these observations indicate probable implication of complement system and miR-146a in course of immune-related diseases and reveal more facts about the pathogenesis of MS. However, further work is needed to determine protein levels of CFH and other possible targets of miR-146a in serum and cerebrospinal fluid of MS patients.

Evaluation of Toxicity Effects of Asafetida on Biochemical, Hematological, and Histological Parameters in Male Wistar Rats.

OBJECTIVES: Asafetida is traditionally used in folklore medicine for the treatment of various ailments. To validate its use in traditional medicine, it is important to evaluate its toxicity in the animal system. Therefore, this study aimed to evaluate the toxicological effects of asafetida in Wistar albino rats. MATERIALS AND METHODS: Acute toxicity tests were conducted by the oral administration of 250, 500, and 1,000 mg/kg body weight of the animal. In chronic study, animals were administered with various doses of asafetida (25, 50, 100, and 200 mg/kg body weight) for a period of 6 weeks. At end of experiment, the effects of asafetida on hematological, renal, and hepatic markers and histological parameters were analyzed. RESULTS: In acute toxicity study, no mortality was seen up to 72 h of the administration of asafetida. No signs of neurological and behavioral changes were noticed within 24 h. In the chronic study, the asafetida intake has changed the hematological parameters such as red blood cell (RBC), white blood cell (WBC), hematocrit (HCT), and platelets. Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased in treated animals. The plasma level of urea and creatinine were not altered by the administration of asafetida throughout the study. Histopathology study indicates hepatotoxicity, but no signs of prominent pathological changes in kidney. CONCLUSIONS: Asafetida did not show any acute toxicity, but chronic administration could have undesirable effects on hepatocytes and hematological factors.

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.

Dysregulation of miR-223, miR-146a, and miR-193a Expression Profile in Acute and Chronic Phases of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice.

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers.

Review of potential spermatogenic and aphrodisiac effects of the Ferula genus.

OBJECTIVE: Men's sexual health plays an important role in male fertility and childbearing, as it is associated with factors such as sexual desire, healthy spermatogenesis, and erectile function. In various cultures, medicinal plants have been utilized to address male sexual issues, including infertility and erectile dysfunction. Despite recent advancements in medical science for treating male impotence, some men opt for herbal supplements as an alternative, given that numerous herbs have the potential to enhance male sexual performance. The Apiaceae family is one of the oldest plant families used for medicinal purposes. Ferula, a genus within this family, comprises approximately 170 different species worldwide. Members of this genus possess numerous therapeutic properties due to the presence of various compounds. This article aims to explore the potential impacts of Ferula plants on the male reproductive system. METHODS: This review article was prepared by searching for terms including Ferula and "aphrodisiac," Ferula and "spermatogenesis," and Ferula and "male reproductive system." Relevant information was gathered through electronic databases, including ISI Web of Knowledge, PubMed, and Google Scholar. RESULTS: The findings indicated that relatively comprehensive studies have been conducted in this area, revealing that certain Ferula species have been employed in folk medicine to boost fertility and libido. Recent research has corroborated these effects. CONCLUSION: It is hoped that new aphrodisiac compounds with fewer side effects can be isolated from Ferula plants in the future.

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.

Therapeutic effect of Ferula assa-foetida oleo-gum resin in rats with letrozole-induced polycystic ovary syndrome.

OBJECTIVE: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. METHODS: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. RESULTS: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. CONCLUSION: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

Therapeutic applications and characteristics of Falcaria vulgaris in traditional medicine and experimental studies.

Objective: Falcaria vulgaris is a herb with various applications in traditional medicine, including treatment of skin and gastric ulcers, liver diseases and gastrointestinal problems. It contains many valuable and important compounds with antioxidants and anti-ulcer properties, including carvacrol, spathulenol, limonene, tannins and saponins. In recent years, besides confirming many of its conventional uses, new beneficial properties of this plant have been identified. The purpose of this review is to investigate the therapeutic applications and botanical characteristics of F. vulgaris in traditional medicine and experimental studies. Materials and Methods: This study was a systematic review using the keywords "Falcaria vulgaris," "Therapeutic properties" and "Animal studies", 100 articles were extracted from various databases, including PubMed, SinceDirect, SID (scientific information database) and google search engines without time limit; after several stages of title monitoring and abstracts review, finally, 70 articles were selected for this study. Results: In traditional medicine of different countries, several therapeutic properties have been reported for F. vulgaris, most of which are attributed to its antioxidant content and the presence of tannins and saponins. In recent decades, many studies have been done to identify and confirm the medicinal properties of F. vulgaris, including antioxidant, antimicrobial and anti-diabetic effects, healing properties of skin and stomach ulcers, and protection of the liver and kidney. Conclusion: F. vulgaris has a variety of biological properties and is used as a valuable plant in medical research that helps to improve health and prevent some diseases.

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.

Evaluating effect of acrylamide and ascorbic acid on oxidative stress and apoptosis in ovarian tissue of wistar rat.

Acrylamide is one of the undesirable compounds created in food, which leads to oxidative stress. Under normal conditions of the body, there is a balance between the production and elimination of free radicals. Imbalance in this process causes oxidative stress. Ascorbic acid has antioxidant properties and can be used to prevent oxidative stress damage. In this study, we considered the effect of acrylamide as a substance that causes oxidative stress and ascorbic acid as an antioxidant. In this experiment, 28 rats were separated into 4 groups (n = 7). Mice were fed orally with acrylamide (10 mg/kg), ascorbic acid (200 mg/kg), both acrylamide and ascorbic acid, and water as AR, AA, AR&AA, and control groups, respectively. Blood and ovarian tissue samples were collected after the final feeding and anesthesia for hematological tests. Blood cells, anti-oxidation status and relative expression of BAX (Bcl-2 Associated X-protein), BCL-2 (B-cell lymphoma-2), Folliculogenesis Specific BHLH Transcription Factor (FIGLA), Follicle Stimulating Hormone Receptor (FSHR), and Klotho (KL) genes were assessed and compared between the study groups. Despite no change in the levels of other factors, white blood cells were significantly different between all groups. The total oxidant and antioxidant index had significant changes in the AR group compared to controls. Glutathione Peroxidase showed the least concentration in the AR group than others although this change was not significant. Gene expression of BAX, BCL-2, FIGLA, FSHR, and KL genes was not significant between the study groups (P > 0.05). The most ratio of BAX to BCL-2 belonged to the AR group compared to other groups. In conclusion, AR probably induces ovarian dysfunction by increasing the proportions of apoptosis-related genes, and the usage of antioxidants like AA can minimize its hazardous effects. However, more research is needed to uncover effective ways to limit AR exposure.

Preventive Effect of Ferula asafoetida Oleo Gum Resin on Histopathology in Cuprizone-Induced Demyelination Mice.

BACKGROUND: Ferula asafoetida is introduced as a valuable remedy for hysteria and some other nervous disorders in Iranian traditional medicine. Asafoetida is an oleo-gum-resin obtained from the exudates of the roots of the Ferula asafoetida. Previous studies have shown that this oleo gum resin has antioxidant, anti-apoptosis, and differentiation properties in the nervous system. The aim of this study was to evaluate the effect of asafoetida on the death of oligodendrocytes and demyelination in male C57BL/6 mice in cuprizone (CPZ)-induced animal model of multiple sclerosis. METHODS: Demyelination was induced by oral administration of rats with the 0.2% CPZ that was added to the usual diet for 8 weeks. Animals intraperitoneally received daily asafoetida at doses of 25 or 50 mg/kg of bodyweight simultaneously. At the end of the weeks, animal brains were removed and fixed to histological studies using Luxol fast blue staining. Asafoetida was screened for its antioxidant activity using 2, 2-diphenyl-1-picylhydrazyl free radical scavenging assay and for its inhibitory activity against lipid peroxidation catalyzed by soybean lipoxygenase. RESULTS: The results of this study showed that asafoetida significantly decreased infiltration rate in both groups of asafoetida 25 and 50 mg/kg, respectively (P < 0.01). Histological evaluations showed the lower demyelination in LFB in the group treated with asafoetida. CONCLUSIONS: The results of this study showed that asafoetida plays a neuro protective role in CPZ models of multiple sclerosis by reducing neuronal demyelination and oligodendrocytes death.

Carvacrol reduces hippocampal cell death and improves learning and memory deficits following lead-induced neurotoxicity via antioxidant activity.

Carvacrol is a monoterpene with neuroprotective effects in several animal models of neurodegeneration, including epilepsy, ischemia, and traumatic neuronal events. In this study, we aimed to examine the effects of carvacrol on neurodegeneration induced by lead acetate in rats. A total of 50 male Wistar rats were divided into five equal groups. The control group received drinking water, while the neurotoxic group was exposed to 500 ppm of lead acetate in drinking water for 40 days. The three remaining groups, which were also exposed to 500 ppm of lead acetate, received carvacrol at doses of 25, 50, and 100 mg/kg orally for 40 days. The Morris water maze test was employed to examine spatial learning and memory. Pathological damage to the hippocampus was determined by Nissl staining. The level of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected using biochemical analysis and the free radical scavenging activity as evaluated by the DPPH test. Administration of carvacrol significantly restored learning and memory impairment induced by lead acetate. Moreover, carvacrol ameliorated neurodegeneration, antioxidative capacity, and lipid peroxidation in the hippocampus of rats exposed to lead. The present results provide a rationale for the inhibitory role of carvacrol in the attenuation of lead-induced neurotoxicity.

Stereological Method for Assessing the Effect of Vitamin C Administration on the Reduction of Acrylamide-induced Neurotoxicity.

INTRODUCTION: Acrylamide (ACR) consumption is increasing all over the world. There are some evidence on the literature about its neurotoxic effect on mature animals, but the effects of ACR on postnatal development have been less studied. The purpose of this study was to evaluate the effects of ACR on development of cortical layer, white matter, and number of Purkinje cells of the cerebellum in rat newborns. METHODS: This study was carried out on 20 female Wistar rats (average weight: 180 g, aged: two months). The rats were divided into four groups. Pregnant rats were orally fed with ACR 10 mg/kg and vitamin C 200 mg/kg. In this study, 6 infants of each group (weighting 32-35 g) were randomly selected at day 21 after birth and placed under deep anesthesia and transcardial perfusion. Their cerebellums were fixed and histopathological changes were evaluated with Hematoxylin and Eosin (H&E) staining and cresyl violet method. The volume of cerebellar cortical layers and number of Purkinje cells were investigated by Cavalieri's principle and physical dissector methods. The obtained data were analyzed by 1-way ANOVA and LSD test using SPSS. P<0.05 considered as statistically significant. RESULTS: The results showed that newborns of ACR-treated female rats have decreased cerebellar weight (P≤0.05) and lower than average number of Purkinje cells (P≤0.001). ACR also decreased the volume of granular and molecular layer and increased the volume of white matter. While the results showed decreased in white matter volume in vitamin C group (P≤0.001). CONCLUSION: ACR induces structural changes in the development of the cerebellar cortical layers in rat newborns, but these changes may be prevented by vitamin C as an antioxidant.

Antiulcer and hepatoprotective effects of aqueous extract of Plantago ovata seed on indomethacin-ulcerated rats.

BACKGROUND: The objective of the study was to investigate the protective effects of aqueous extract of Plantago ovata seed (AEPOS) on peptic ulcer induced by indomethacin (IND) in rats. METHODS: Rats (250-300 g) were divided into three groups (5 rats in each group). Gastric ulcer was induced by a single oral gavage of 48 mg/kg IND. The first group received only 5% sodium bicarbonate orally (5 ml/kg) whereas the control (IND) group received only single oral dose of 48 mg/kg IND. The third group was pretreated with an extract (100 mg/kg) for 4 days. At the end of the 4th day, rats were kept fasted for 24 h before administration of IND 48 mg/kg. The rats were sacrificed 4 h after oral administration of IND and their stomach and liver were fixed in formalin (10%) and sections of 5 mm in diameter were prepared. Histological and morphological characteristics of stomach and liver were assessed using hematoxylin and eosin (H&E) staining. RESULTS: AEPOS (100 mg/kg) showed a significant (p < 0.05) reduction in microscopic and macroscopic ulcer index as compared to the IND group. Histological analysis indicated that AEPOS has hepatoprotective effect and can prevent mucosa damage in stomach. CONCLUSION: Results revealed that AEPOS has anti-ulcer and hepatoprotective effects.

Antitumor effect of Ferula assa foetida oleo gum resin against breast cancer induced by 4T1 cells in BALB/c mice.

BACKGROUND: Ferula assa foetida commonly consumed as a healthy beverage has been demonstrated to have various biological activities, including antioxidation, anti-obesity and anti-cancer. OBJECTIVE: Our study aims to investigate the antitumor effect of asafoetida in vivo using mouse mammary carcinoma 4T1 cells. MATERIALS AND METHODS: In the study, female BALB/c mice were divided into two groups (n = 6), which were control (untreated) and other group of mice with breast cancer treated with 100 mg/kg of asafoetida, respectively, by oral gavage. All mice were injected into the mammary fat pad with 4T1 cells (1 × 105 4T1 cells/0.1 ml of phosphate buffer solution). Asafoetida was administered on day 15 after the tumor had developed for 3 weeks. At end of experiment, tumor weight, tumor volume and tumor burden were measured and lung, liver, kidney and tumor were harvested and sections were prepared for histopathological analysis. Lipoxygenase inhibitory and antioxidant activity of asafoetida was also determined. RESULTS: Our results showed that treatment with asafoetida was effective in decreasing the tumor weight and tumor volume in treated mice. Body weight significantly increased in female BALB/c mice against control. Apart from the antitumor effect, asafoetida decreased lung, liver and kidney metastasis and also increased areas of necrosis in the tumor tissue respectively. CONCLUSIONS: The present study demonstrated that asafoetida has potent antitumor and antimetastasis effects on breast cancer and is a potential source of natural antitumor products.

Prenatal Caffeine Exposure Impairs Pregnancy in Rats.

BACKGROUND: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world's population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL) and abnormality in pregnant rats. MATERIALS AND METHODS: In this experimental study, 40 female albino rats (170-190 g) were randomly divided into two experimental and two control groups (n=10/each group). In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day) on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. RESULTS: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05). There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. CONCLUSION: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

Effect of titanium dioxide nanoparticles on the stereological parameters of the dentate gyrus and the morphology of granular hippocampal neurons in mice / Efecto de las nanopartículas de dióxido de titanio sobre los parámetros estereológicos del giro dentado y morfología de las neuronas granulares del hipocampo en ratones

SUMMARY: This study aims to investigate the Effects of Titanium dioxide nanoparticles (TiO2 NPs) on the stereological parameters in the dentate gyrus and the morphology of granular hippocampal neurons in adult mice. Adult male mice (n=20, weight average: 45 g) were randomly divided into four groups including: group receiving saline (controls), low-dose (LD) 2.5 mg/kg TiO TiO2 NPs, medium-dose (MD) 5 mg/kg TiO2 NPs and high-dose (HD) 10 mg/kg TiO2 NPs, daily using gavage for 35 days. To estimate the volume of the hippocampus, dentate gyrus, and sub-layers of dentate gyrus the Cavalieri principle was used. The physical dissector was used to determine the numerical density of dentate gyrus granular cells. For analyzing the morphology of dentate gyrus granular cells the qualitative Golgi staining was used. Our data showed that the total volume of the hippocampus, dentate gyrus and its sublayers including molecular, granular and polymorph in TiO2 treated mice decreased significantly compared to the control group. Moreover, the total number and numerical density of dentate gyrus granular sub layer cells showed a significant reduction in all three experimental groups compared to the control group. The granular cells of the dentate gyrus had shorter dendritic length and decreased dendritic branches in the TiO2-treated in comparison with the control mice. These data can justify the disorders related to memory, learning and hippocampus neurons damages due to using of TiO2 NPs.

RESUMEN: En este estudio se analizaron los efectos de las nanopartículas de dióxido de titanio (TiO2 NP) sobre los parámetros estereológicos en el giro dentado y la morfología de las neuronas granulares del hipocampo en ratones adultos. Se dividieron aleatoriamente ratones machos adultos (n = 20, promedio de peso: 45 g) en cuatro grupos: grupo que recibió solución salina (controles), dosis baja (LD) 2,5 mg/kg NP de TiO2, dosis media (MD) 5 mg/kg de NP de TiO2 y dosis altas (HD) de 10 mg/kg de NP de TiO2, por vía utilizando sonda durante 35 días. Para estimar el volumen del hipocampo, el giro dentado y las subcapas del giro dentado se utilizó el principio de Cavalieri. Se utilizó el disector físico para determinar la densidad numérica de las células granulares del giro dentado. Para analizar la morfología de las células granulares del giro dentado se usó la tinción cualitativa de Golgi. Nuestros datos mostraron que el volumen total del hipocampo, el giro dentado y sus subcapas, incluyendo la molecular, granular y polimorfos, en ratones tratados con TiO2, disminuyó significativamente en comparación con el grupo de control. Además, el número total y la densidad numérica de las células de la subcapa granular del giro dentado mostró una reducción significativa en los tres grupos experimentales en comparación con el grupo control. Las células granulares del giro dentado tenían una longitud dendrítica menor y ramas dendríticas disminuidas en los ratones tratados con TiO2 en comparación con los ratones del grupo control. Estos datos pueden justificar los trastornos relacionados con la memoria, el aprendizaje y los daños en las neuronas del hipocampo debido al uso de NP de TiO2.

Effect of Ferula assa-foetida oleo gum resin on spermatic parameters and testicular histopathology in male wistar rats.

BACKGROUND: In Ayurveda and traditional medicines of different countries such as Iran, America and Brazil, asafoetida has been used as an aphrodisiac agent. OBJECTIVE: The present study was aimed to evaluate the effectiveness of asafoetida on spermatic and testicular parameters in treated rats. MATERIALS AND METHODS: A total of 30 male Wistar rats divided equally to five groups (one control and four test groups receiving 25, 50,100 and 200 mg/kg asafoetida respectively). After 6 weeks, a small part of the cauda epididymis of each rat was dissected, and the spermatic parameters were evaluated for at least 200 spermatozoa of each animal. Testis of all rats was harvested for pathologic examination. The testosterone concentration of serum was also determined. Data were statistically assessed by one-way ANOVA and value of P < 0.05 was considered as the level of significance. RESULTS: This study indicated that the asafoetida significantly increased the number and viability of sperms (P < 0.05). Histological study showed that spermatogenesis process and numbers of Leydig cells were increased with increasing the dose, but the Leydig cells become vacuolated. Johnsen score in experimental groups was increased compared to control although this difference was not significant (P > 0.05). CONCLUSION: Asafoetida showed a positive effect on spermatic parameters although the histopathological effects on the testis were observed, particularly at high doses.