Estrogenic Effect of Bambusa arundinacea, Trichosanthes dioica and Punica granatum on Rats

Background: Phytoestrogens have recently become a hot topic among scientists. Phytoestrogens’ estrogen-like properties have led to their widespread use in the reproductive system. The aim of this research was to see whether the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum had any estrogenic activity in female wistar rats. Methods: In female wistar rats, the estrogenic effect was studied using a uterotropic assay, vaginal cytology and vaginal opening. In ovariectomized immature and mature female wistar rats, a 400 mg/kg body weight (b.w.) dose of ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum was given. Result: When compared to ovariectomized control rats, the uterine wet weight increased significantly. The estrogen-treated rats had only cornified epithelial cells, indicating the existence of oestrogen, as well as 100% vaginal opening. At 400 mg/kg b.w., the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum demonstrated promising estrogenic activity, as evidenced by uterotropic assays, vaginal opening measurements and histopathological changes. As a result of this research, it’s possible to infer that the ethanolic extract of Bambusa arundinaceae, Trichosanthes dioica and Punica granatum play an important role in estrogenic activity in female rats.

Combination of nanosomal form of doxorubicin, interferon alpha, and nitroglycerin in the threatment of 101.8 glioblastoma in Wistar rats

The search for effective approaches to the treatment of patients with glioblastoma is one of the difficult tasks of neurooncology; standard methods of therapy show limited results. Combined therapy, which includes different antitumor mechanisms, can increase its effectiveness. The combination of PLGA nanoform of doxorubicin (Dox-PLGA), antitumor cytokine — interferon alfa (IFN-α), and nitrogen oxide (NO) donor nitroglycerin (NG) was investigated in this work both in vitro (rat C6 glioma) and in vivo (rat 101.8 glioblastoma). MTT assay in the C6 cell line showed great cytotoxicity and antiproliferative effect of the combination of IFN-α with Dox-PLGA and NG. The lowest tumour cell survival was observed when using a high dose of IFN-α (10 ng/ml) in mono-mode. In the in vivo experiment, 32 female Wistar rats with 101.8 glioblastoma received therapy in the following modes: Dox-PLGA + NG; Dox-PLGA + IFN-α; Dox- PLGA + IFN-α + NG. There was a significant increase in median survival and life expectancy (ILE) in all groups receiving therapy compared to the group that did not undergo treatment. The longest median lifespan (27 days), survival up to 100 days (1 animal), ILE (131%) were observed in animals that received the combination Dox-PLGA + IFN-α+ NG, compared to the group without treatment, in which the median lifespan was 15 days. Thus, the therapy of experimental glioblastoma both in vivo and in vitro with the combination of Dox-PLGA + IFN-α + NG has the most pronounced therapeutic and antitumor effect, which must be taken into account when developing new more effective methods of treating human glioblastomas.

nxiolytic Effect of the Hydro-alcoholic Extract of Anethum Graveolens Seed in Adult Female Wistar Rats: Modulation of GABA Receptors

Background: Along with industrial development and the increasing social complexity of societies, anxiety is one of the most prevalent psychological disorders. Medicinal plants are considered as an enrichment source of ingredients with biological activity. Objectives: The aim of this study was to evaluate the anxiolytic effect of Anethum Graveolens seed (AGS) and the possible involvement of Gamma-Aminobutyric Acid (GABA)-ergic system in the AGS effect. Materials & Methods: In the present experimental study, 64 female Wistar rats were divided into eight groups and received various concentrations of hydroalcoholic extract of AGS. To measure the level of anxiety, an elevated plus maze was used in a way that the animal’s head turned to an open arm. Prior to the injections of AGS extract, the GABA receptor antagonist was used. The results were analyzed by one-way analysis of variance using IBM SPSS v. 16. Results: Dose-response experiments showed that the AGS extract significantly decreased the anxiety indices compared to the control group (P<0.05). To analyze locomotor activity, our data showed that AGS extract at 0.1, 1, and 10 mg/kg could significantly increase locomotor activity compared to the control group (P<0.001). Pentylenetetrazol (PTZ (+extract significantly decreased the anxiolytic effect of AGS extract (P<0.01). Conclusion: Considering the anti-anxiety effects of AGS extract and a reduction in this effect caused by PTZ, part of the anti-anxiety effect of extract might be assumed via its interaction with GABA-ergic receptors. Further experimental trials; however, are required for the establishment of the anti-anxiety impact of AGS.

Toxicological safety of VOHO Hemp Oil; a supercritical fluid extract from the aerial parts of hemp

VOHO Hemp Oil (Verdant Nature LLC (in collaboration with HempFusion)) is an extract of the aerial parts of hemp (Cannabis sativa L) manufactured using a supercritical CO2 extraction process. The results of four safety studies are reported here including a bacterial reverse mutation assay, an in vivo mammalian micronucleus study, a maximum tolerated dose study in rats and a 90-day repeat dose subchronic toxicity study in rats. VOHO Hemp oil can contain up to 30% phytocannabinoids and less than 0.2% is tetrahydrocannabinol (THC). VOHO Hemp Oil was found to be non-mutagenic in the bacterial reverse mutation assay and was negative for inducing micronuclei in the rat bone marrow micronucleus assay. The maximum tolerated dose in male and female Wistar rats was 2250 mg/kg bw/day. A 90-day repeat dose study was conducted in male and female Wistar rats according to OECD Guideline 408 and included a 21-day recovery period. The doses used in the study were 0, 25, 90 and 324 mg/kg bw per day in the main study, and in the recovery phase a control and 324 mg/kg bw/day group were included. One mortality was reported during the study, a high dose female, and test substance-related adverse clinical signs were reported in the high dose group. Other test substance-related changes noted in the high dose group included changes in body weights, activated partial thromboplastin time (APTT) values, and in absolute and relative organ weights. Based on the results of the study, the no observed adverse effect level (NOAEL) for VOHO Hemp Oil was determined to be 90 mg/kg bw/day in both male and female Wistar rats.

Cortical Neurons and Astrocytes in Intrauterine Ethanol Exposure: The Role of Exposure Time and Postnatal Timeline

Background: The state of cortical neurons and astrocytes are pointers to the health of the brain. These cells are morphologically distorted by alcohol exposure. Intrauterine alcohol exposure remains a challenge with perinatal consequences. The role of exposure time and postnatal timeline on the degree of cortical cell derangement remains a subject of controversy till date. This study therefore examines alcohol exposure and postnatal changes on brain weight, cortical neurons and astrocytes at different developmental periods. Methods: Twenty mature female Wistar rats were time-mated and grouped into 4 groups. Group 1 (control) received distilled water (2 mL/kg), Groups 2, 3 and 4 were administered 2.5 mL/kg of 20% ethanol orally on the 4th, 11th and 18th days of gestation respectively. Rats produced litters and pups' brains were harvested and processed for H&E and Golgi Cox stains at the 3rd and 6th postnatal week. Neuronal and astrocytic densities in the cerebral cortex were evaluated. Results and Conclusion: There was statistically significant increase (p<0.05) in the density of degenerating neurons at the third postnatal week and sixth postnatal weeks in the experimental groups when compared with the control. There was also statistically significant increase (p<0.05) in astrocytic density in groups 2 and 4 at the 3rd postnatal week. There was no statistically significant difference (p>0.05) in the astrocytic densities across groups at the sixth postnatal week. It was concluded that intrauterine alcohol exposure in any of the developmental periods resulted in postnatal neuronal degeneration which persisted till the 6th week. However, increased astrocytic densities is a feature of 1st and 3rd trimester alcohol exposure noted in the 3rd but absent in the 6th postnatal week.

Kefir as a Prevention of Arsenic-mediated Toxicity in Uterine Female Rats

Background: kefir is a fermented milk product that demonstrates numerous health benefits including antioxidant and immunomodulatory. Aim: to study the protective effect kefir on the expression of estrogen receptor alpha (ERα) in endometrial stromal cells and endometrial thickness on female rats that were exposed to arsenic. Methods: twenty-five female Wistar rats (Rattus norvegicus) were divided into five groups (CRL, As, T1, T2, T3). Control group (given a normal diet), As group (given the normal diet and exposed to arsenic trioxide 2 mg/kgBW/day). The T1; T2; T3 were exposed to arsenic trioxide 2 mg/kgBW/day and treated with different doses of kefir (1.25; 2.5; and 5 mL/kgBW/day, respectively) for 35 days. The rats of group As treated with arsenic trioxide only and group CRL served as control with normal feed in water. Cytological samples were taken after 35 days of treatment and examined every day to see the rat oestrus phase, and the proestrus phase of the oestrous cycle was chosen for termination. Uterine tissue fixed in 10% neutral buffered formalin for tissue preparation. ERα expression in endometrial stromal cells was analized using immunohistochemistry method, endometrial thickness was observed using histopathological methods. Results: significant reduction of ERα expression in endometrial stromal cells and endometrial thickness in female rats exposed to arsenic were observed in groups on treated rats (p ≤ 0.000; 0.009, respectively). Conclusion: the administration of kefir in female Wistar rats exposed to arsenic had shown significantly differences on ERα expressions and endometrial thickness. The smallest dose of kefir (1.25 mL/kgBW/day) could increase ERα expression and endometrial thickness in female Wistar rats with arsenic exposure. Therefore kefir has protective effect related to female reproductive system.

Change of Embryotoxic Effects of Metal Citrates Depending on the Duration of Their Introduction

Given the increase in cadmium in the environment (air, soil, water) through modern industrial processes, the absorption of significant amounts from cigarette smoke is relevant to studying the effect of cadmium compounds on embryogenesis. The purpose of the study: experimental study and comparison of embryolethality and embryotoxicity of metal citrates depending on the duration of their intragastric administration (during 13 and 20 days of gestation). Materials and methods. The study was performed on 120 white adult female Wistar rats that weigh 170-200 g. They were divided into 6 groups due to the intragastric administration of solutions of the studied metals – rats treated with citrates: cadmium at a dose of 1.0 mg/kg – 1st group (nfemale = 20, nemb = 166); cadmium at a dose of 1.0 mg/kg and cerium (1.3 mg/kg) – 2nd group (nfemale = 20, nemb = 185); cadmium in a dose of 1.0 mg/kg and germanium (0.1 mg/kg) – 3rd group (nfemale = 20, nemb = 184); cadmium at a dose of 1.0 mg/kg and zinc (1.5 mg/kg) – 4th group (nfemale = 20, nemb = 179); cadmium at a dose of 1.0 mg/kg and nanocomposite (iodine + sulfur + selenium) at a dose of 2.0 mg/kg – 5th group (nfemale = 20, nemb = 180), 6th group – control (nfemale = 20, nemb = 212) – proportional volume of sterile saline in the same way. Females were divided into 2 subgroups of 10 animals each, depending on the duration of administration of test substances. The embryotoxic and embryolethal effects of the test substances were evaluated according to generally accepted criteria, which were calculated according to well-known formulas. Results and discussion. Cadmium compounds harm the embryogenesis of rats in the experimental groups and increase the rates of embryolethality. The most pronounced differences in these parameters concerning the control were found in animals with isolated exposure to cadmium citrate: the rates of total embryonic mortality increased by 4.0 times in both study periods of embryogenesis and 20% from the 13th to the 20th day; increased pre-implantation mortality by 6.0 times with an increase in post-implantation mortality by 3 times on the 13th day and by 15.0 times and 2.8 times on the 20th day of embryogenesis, respectively. Depending on the duration of introduction, the indicators of pre-implantation mortality increased by 25.0% with an increase in post-implantation mortality by 22.2% in the same period. The experimental group of exposure to cadmium citrate at a dose of 1.0 mg/kg recorded the lowest indicators of the number of live fetuses and intrauterine survival with the highest resorption rate studied of embryonic development. At the same time, in the groups of combined exposure to cadmium citrate with metal citrates, a decrease in the indicators of total embryonic mortality was 50.0% - 30.0%, pre-implantation mortality – 50.0% - 25.0%, post-implantation mortality – 60.0% - 44.4 % and increase in the number of fetuses per female – 12.7% - 25.3%. Conclusion. Analysis of the results shows a pronounced embryotoxic effect of cadmium citrate at a dose of 1.0 mg/kg on the processes of embryogenesis, which is a significant increase in overall embryonic mortality, preimplantation, and postimplantation mortality compared with the control group in all studied terms. In the groups of combined action of cadmium citrate with metal citrates, the data obtained indicate a decrease in the accumulation of cadmium under the influence of the studied citrates, which allows them to be considered as potential bioantagonists of cadmium citrate

Resistance-exercise training attenuates LPS-induced astrocyte remodeling and neuroinflammatory cytokine expression in female Wistar rats

Neuroinflammation is an early detectable marker of mild cognitive impairment, the transition state between normal cognition and dementia. Resistance-exercise training can attenuate the cognitive decline observed in patients with mild cognitive impairment. However, the underlying mechanisms of resistance training effects are largely unknown. To further elucidate mechanisms of the known cognitive health benefits from resistance-exercise training, we tested if three weeks of resistance-exercise training could ameliorate lipopolysaccharide-induced neuroinflammation. Five-week-old female Wistar rats received intracerebroventricular injections of lipopolysaccharides to induce neuroinflammation and cognitive impairment. Rats then underwent three weeks of progressive ladder climbing to recapitulate resistance-exercise training in humans. Cognition was assessed towards the end of the training period by novelty object recognition testing. Neuroinflammation was measured one and 24-hours after the last resistance-exercise training workout. Resistance-exercise training ameliorated cognitive impairment, diminished lipopolysaccharide-induced neuroinflammatory cytokine expression, and attenuated astrocyte remodeling in the dentate gyrus 24-hours post exercise. Here, we provide evidence that the ladder-climbing model of resistance-exercise training in rats can improve cognition as early as three weeks. Additionally, these data support the hypothesis that resistance exercise can reduce lipopolysaccharide-induced neuroinflammation in the dentate gyrus.

Effect of Penicillin on Reproductive Function in Female Wistar Rats

This study was designed to investigate the effect of penicillin on reproductive function in female Wistar rats. Fifteen female rats (120 – 160 g) were used for the estrous cycle and histopathological studies. Penicillin (17.14 mg/kg) was administered orally on daily basis for 21 and 50 days respectively for the estrous cycle and histological studies. Estrous cycle was carried out using the technique of Marcondes et al., histologies of the ovaries and uteri were also carried out. Data were analysed using descriptive statistics and student’s t-test at p=0.05. Treatment of rats for 21 days with penicillin (17.14 mg/kg) produced significant (p<0.05) increments in the estrous and metestrous phases as well as a significant (p<0.05) reduction in the proestrous phase of the estrous cycle relative to their respective controls. The histopathological study presented with a moderate endometrial congestion. It can therefore be concluded that penicillin probably has a pro-fertility effect with a moderate deleterious effect on the uteri at histological level in female Wistar rats.