Female Swiss Mice Research Articles

Antimanic-like effect of dipyridamole in the methylphenidate-induced hyperlocomotion.

Adenosinergic system has been implicated in the pathophysiology of bipolar disorder and drugs that affect adenosine neurotransmission have shown some efficacy as add-on therapy in manic patients. Thus, the aim of the present study was to screen adenosinergic drugs for antimanic-like effect in methylphenidate (MPH)-induced hyperlocomotion in mice. Male and female Swiss mice received a single allopurinol (50 and 200 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) administration before an acute MPH challenge (5mg/kg, sc). In experiments with repeated treatment, male mice received a daily administration of allopurinol (25 and 50 mg/kg, ip), dipyridamole (20 mg/kg, ip), or inosine (50 mg/kg, ip) for 14 days. Finally, pretreatment with aminophylline (2mg/kg, sc), an unspecific adenosine receptor antagonist, was used to evaluate a putative adenosinergic mediation. Locomotor activity was measured in the automated activity chamber for 20 min. Acute and repeated dipyridamole reduced the increase in locomotor activity induced by MPH, while allopurinol and inosine had no effect. Aminophylline blocked the effect of dipyridamole in MPH-induced hyperlocomotion. The present results suggest that dipyridamole may have an antimanic-like effect through adenosine receptors and reinforce the proposal that the adenosine system may be an interesting target for new antimanic drugs.

Does Fried Street Food (Kokor) affect Lipid Profiles and bodyweight? The Finding from Swiss Albino Mice

Background: Foods fried in palm oil on the streets change the oil composition and produce toxic byproducts. Even though the health implications of fried street food are not fully understood, Ethiopians frequently consume these items. Therefore, this study evaluated the impact of street kokor fried in palm oil on mice's lipid profiles and body weight. Methods: The experiment involved 32 Swiss Albino male and female mice, which were randomly separated into four groups with equal male and female subgroups. The experimental groups, Group II, Group III, and Group IV, got 10%, 20%, and 30% of the daily food intake, respectively. In contrast, the control group (Group-I) received only pellets and a vehicle (water). The mice were killed at the end of the sixth weeks after recieving a diethyl ether anesthetic. Once their blood was drawn through a heart puncture, lipid profile tests were performed on it. Results: In this experiment, the amount of street kokor cooked in palm oil had a significant impact on the mice' body weight [F (3, 24) = 13.841, p = 0.001] and all of the mice in the experimental groups had significantly lower body weights than the mice in Group I (the control group) (P 0.05). Similarly, the dose of palm oil fried street kokor had a significant effect on serum triglyceride (TG) [F (3, 24) = 17.72, p = 0.001], serum low-density lipoprotein (LDL) [F (3, 24) = 90.344, p = 0.001], serum high-density lipoprotein (HDL) [F (3, 24) = 25.38, p = 0.001] and serum total cholesterol (TC) level of the mice [F (3, 24) = 257.480, p = 0.001]. The experimental group mice's lipid profiles, except serum HDL level, were increased significantly compared with the control group mice (P < 0.05). Conclusion: Mice's body weight fell and serum lipid profiles were affected by palm oil-fried street kokor. This study found that palm oil-fried street kokor dramatically decreased mice's body weight. Furthermore, ingesting kokor cooked in palm oil significantly and proportionally elevated mice's serum lipid profiles (TG, LDL, and TC), but it also dramatically and inversely decreased HDL levels.

Carrageenan-Induced Acute Inflammation on Back-Skin of Mice: Histopathological Features, Number of Inflammatory Cells, and Expression of COX-2, COX-1, and IL-6

Carrageenan is a sulfated polysaccharide obtained from red seaweed (Rhodophyceae) and can trigger inflammatory activation in both humans and laboratory animals. This study aimed to investigate the expression of cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and interleukin-6 (IL-6) and the number of inflammatory cells (neutrophil) involved in a carrageenan-induced acute inflammatory model in the back skin of mice. Paraffin blocks from the back skin of female Swiss mice aged 8 weeks were used in this study. The back-skins of 4 groups of 5 mice in each group were subcutaneously injected with 1%, 2%, and 4% carrageenan powder in 0.9% buffer saline and 0.9% buffer saline as control. Skin samples on paraffin blocks were taken 6 hours after carrageenan injection. Furthermore, paraffin blocks were stained with hematoxylin-eosin (HE) to count the number of inflammatory cells. Immunohistochemistry staining using anti-COX-2, COX-1, and IL-6 antibodies was performed to determine the role of inflammatory mediators. The results showed that the number of inflammatory cells (neutrophils) increased significantly following an increase in carrageenan concentrations. The COX-2, COX-1, and IL-6 expressed by inflammatory cells increased significantly at carrageenan concentrations of 1% to 4%. Histopathological features supported the results obtained from the calculation of the number of inflammatory cells and the expression of COX-2, COX-1, and IL-6. The inflammatory markers consisting of COX-2, COX-1, and IL-6 were expressed on the back skin of mice at 6 hours post-injection with 1% to 4% carrageenan. It can be concluded that carrageenan can be used for an acute inflammatory model of the back skin of a mouse. This inflammation model is intended to facilitate the evaluation or measurement of therapeutic and inflammatory responses when test substances are administered topically or transdermal.

Development and Evaluation of Curcumin-based Transferosomal Gel for Wound Healing

Background: Recently, transferosomes have been discovered to have the potential for transdermal delivery. Curcumin is a bioactive molecule with anti-inflammatory and antioxidant properties, but it has low water solubility and poor skin absorption. The biological response to damage caused by diverse stimuli is known as the inflammatory process. Cyclodextrins are cyclic (-1, 4)-linked oligosaccharides of -D-glucopyranose with a hydrophilic outer surface and a hydrophobic center cavity. Aim: The aim of the study was to develop a curcumin-loaded transferosomal gel to improve the wound healing process. The study has focused on advancing the area of traditional medicine in the field of pharmaceutics by using curcumin in the form of transferosomes to enhance wound healing. Method: Firstly, curcumin was used to synthesize the transferosomes. Secondly, the transferosomes were converted into a transferosomal gel as an alternative for wound healing. Characterization and in vivo investigation were carried out on female Swiss mice. Results: Unpaired Student’s t-test was used to determine the statistical significance at p < 0.5 using UV exposure schedules. All values have been expressed as mean ± SEM calculated by ANOVA with a significant difference among means at P < 0.05. Conclusion: The study has indicated curcumin to be successfully entrapped in transferosomes in order to formulate the gel with powerful wound healing properties.

Evaluation of antioxidant, anti-inflammatory, anticancer activities and molecular docking of Moringa oleifera seed oil extract against experimental model of Ehrlich ascites carcinoma in Swiss female albino mice

The current research intended to evaluate the antitumor properties of Moringa oleifera oil extract (MOE). Fifty-six female Swiss albino mice were employed in this study. Animals were assigned into four groups: control (C) group, moringa oil extract (MOE) group administered (500 mg/kg b. wt) MOE daily via gavage, Ehrlich ascites carcinoma (EAC) group and EAC group administered daily with (500 mg/kg b.wt) MOE for two weeks (EAC/MOE). The results showed that MOE significantly ameliorated the EAC increase in body weight and reduced the EAC cell viability. In addition, they upgraded the levels of hepatic and renal functions, inflammatory cytokines, oxidative stress markers and EAC-induced hepatic and renal histopathological changes. Treatment of EAC with MOE induced antitumor, anti-inflammatory and antioxidant effects and normalized most of the tested parameters besides the histopathological alterations in both renal and hepatic tissues. HPLC for the MOE identified Cinnamic acid, Ellagic acid, Quercetin, Gallic acid, Vanillin and Hesperidin as major compounds. The molecular docking study highlighted the virtual binding of the identified compounds inside the GSH and SOD proteins, especially for Quercetin which exhibited promising binding affinity with good interactive binding mode with the key amino acids. These results demonstrate that the antitumor constituents of MOE against EAC induced oxidative stress and inflammation by preventing oxidative damage and controlling EAC increase.

Maternal exercise during pregnancy modulates genotoxicity caused by high fructose consumption in mice offspring.

Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.

Minimal effective dose of bedaquiline administered orally and activity of a long acting formulation of bedaquiline in the murine model of leprosy.

Bedaquiline (BDQ), by targeting the electron transport chain and having a long half-life, is a good candidate to simplify leprosy treatment. Our objectives were to (i) determine the minimal effective dose (MED) of BDQ administered orally, (ii) evaluate the benefit of combining two inhibitors of the respiratory chain, BDQ administered orally and clofazimine (CFZ)) and (iii) evaluate the benefit of an intramuscular injectable long-acting formulation of BDQ (intramuscular BDQ, BDQ-LA IM), in a murine model of leprosy. To determine the MED of BDQ administered orally and the benefit of adding CFZ, 100 four-week-old female nude mice were inoculated in the footpads with 5x103 bacilli of M. leprae strain THAI53. Mice were randomly allocated into: 1 untreated group, 5 groups treated with BDQ administered orally (0.10 to 25 mg/kg), 3 groups treated with CFZ 20 mg/kg alone or combined with BDQ administered orally 0.10 or 0.33 mg/kg, and 1 group treated with rifampicin (RIF) 10 mg/kg. Mice were treated 5 days a week during 24 weeks. To evaluate the benefit of the BDQ-LA IM, 340 four-week-old female swiss mice were inoculated in the footpads with 5x103 to 5x101 bacilli (or 5x100 for the untreated control group) of M. leprae strain THAI53. Mice were randomly allocated into the following 11 groups treated with a single dose (SD) or 3 doses (3D) 24h after the inoculation: 1 untreated group, 2 treated with RIF 10 mg/kg SD or 3D, 8 treated with BDQ administered orally or BDQ-LA IM 2 or 20 mg/kg, SD or 3D. Twelve months later, mice were sacrificed and M. leprae bacilli enumerated in the footpad. All the footpads became negative with BDQ at 3.3 mg/kg. The MED of BDQ administered orally against M. leprae in this model is therefore 3.3 mg/kg. The combination of CFZ and BDQ 10-fold lower than this MED did not significantly increase the bactericidal activity of CFZ. The BDQ-LA IM displayed similar or lower bactericidal activity than the BDQ administered orally. We demonstrated that the MED of BDQ administered orally against M. leprae was 3.3 mg/kg in mice and BDQ did not add significantly to the efficacy of CFZ at the doses tested. BDQ-LA IM was similar or less active than BDQ administered orally at equivalent dosing and frequency but should be tested at higher dosing in order to reach equivalent exposure in further experiments.

Transgenerational epigenetic effects imposed by neonicotinoid thiacloprid exposure.

Neonicotinoids are a widely used class of insecticides that are being applied in agricultural fields. We examined the capacity of a neonicotinoid, thiacloprid (thia), to induce transgenerational effects in male mice. Pregnant outbred Swiss female mice were exposed to thia at embryonic days E6.5-E15.5 using different doses. Testis sections were used for morphology analysis, ELISAs for testosterone level analysis, RT-qPCR and RNA-seq for gene expression analysis, MEDIP-seq and MEDIP-qPCR techniques for DNA methylation analysis, and Western blot for a protein analysis. The number of meiotic double-strand breaks and the number of incomplete synapsed chromosomes were higher in the thia 6-treated group of F3 males. Genome-wide analysis of DNA methylation in spermatozoa revealed that differentially methylated regions were found in all three generations at the promoters of germ cell reprogramming responsive genes and many superenhancers that are normally active in embryonic stem cells, testis, and brain. DNA methylation changes induced by thia exposure during embryonic period are preserved through several generations at important master regulator regions.

Carbetocin Inhibits Behavioral Sensitization to Ethanol in Male and Female Mice, Independent of Corticosterone Levels.

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT's properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT's impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice.

Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Development And Evaluation of topical liposomal preparation of Walnut oil and tamarind seed oil against ageing

BackgroundRevamp of liposomal preparation inimical ageing by using a splendid treasure of herbal drugs includes non-prescription and prescription upshot. Liposomal therapy stands at the forefront of cutting-edge cosmeceutical innovation. It involves a sophisticated, bi-layered delivery system designed for the precise infusion of walnut oil and tamarind seed oil into the skin. This innovative approach effectively combats the signs of ageing, whether they are the result of a sedentary lifestyle or genetic factors within one's family history. PurposeThe current study focuses on exploring the area of traditional systems of medicine in the field of pharmaceuticals to achieve the combined effect of walnut oil [F1] and tamarind seed oil [F2] in the form of liposomal preparation against ageing. MethodsLiposomes of walnut oil and tamarind seed oil were developed by using a rotary vacuum evaporator, and microscopy of the formulated liposomes was done using a Digicam microscope, which provided a microscopic view that both formulated liposomes are spherical, but F1 liposomes are more dense and tactile than F2, and the F2 liposomal formulation has more vesicles than F1. In-vitro drug release studies of F1 and F2 were done by diffusion cells while using a dialysis membrane with buffer medium 6.8. Further characterization techniques like SEM and FTIR were used to investigate the size range with the clear shape of the particles and to obtain a clear peak that matched the pure drug, which shows that it has retained its pharmacological properties. The final step was directed towards the preparation of topical anti-ageing cream by combining F1 and F2 to obtain the synergistic effect, and the formulation cream was successfully visualised under a projection microscope at a magnification of 10x, which reveals that spherically droplet vacuoles are present with a soft texture and a creamy, whitish colour. Last but not least, a 14-day animal study was conducted on female Swiss mice from the authorised animal laboratory departmental animal house at Integral University. The studies were conducted in 3 groups: G1 was given saline as a control, G2 was given Olay as a topical application, and G3 was given the test cream. The anti-ageing potential of the formulated cream was evaluated by skin compliance studies using UV exposure. ResultsWalnut oil and tamarind seed oil-based liposomes were formulated after placebo selection, i.e., F1 and F2, and the microscopic view of F1 sphere-shaped vesicles is larger, brighter, and more dense than F2, and the sphere-shaped vesicles of F1 and F2 contain phospholipid bilayers composed of soyalecthin, which helps to deliver drugs at a specific site. The pH of two formulations, F1 and F2, was determined by storing them at different temperatures, 350°C and 450°C. The pH resultant values were in the range of 5.8 to 6.9, which means that the formulated liposomes are ideal for skin function. ​In-vitro ​drug release studies of F1 and F2 data revealed that F1 shows less drug release than F2 at 35 min, which is less than 100%. This specified study was done to identify the time that was taken to release the drug. The structural analysis of liposomes F1 and F2 was done by the highly characterised technique of SEM, and the result revealed that F1 and F2 were in a spherical shape. F1 liposome was 5 ​μm in diameter, while F2 liposome was 1 ​μm in diameter, which means that they lie in the bilayer liposomal range. FTIR is an important parameter to analyse the functional group and also to identify the peak of the pure drug that is similar to the excipient for retaining the pharmacological action, so here F1 and F2 liposomes are similar to the pure drug. The topical preparation of liposomes F1 and F2 was decided to formulate cream that is easy to use and store. The combining anti-ageing creams of F1 and F2 were visualised under a projection microscope, and the view of the liposomal cream revealed sphere-shaped vesicles. As a result of skin compliance studies, ∗∗G3 is significantly more significant than G1 and ∗G2 is significantly more significant than G1. The anti-ageing evaluation study stated that ∗∗G3 is much more significant than G2, and ∗G2 is much more significant than G1. ConclusionThe present study indicates that walnut oil and tamarind seed oil were successfully entrapped in a liposomal formulation in the form of cream. The characterization studies reveal that they are potent against ageing.

Modulation of Gut Microbiome Community Mitigates Multiple Sclerosis in a Mouse Model: The Promising Role of Palmaria palmata Alga as a Prebiotic.

Red marine algae have shown the potential to reduce inflammation, influence microbiota, and provide neuroprotection. To examine the prebiotic properties of Palmaria palmata aqueous extract (Palmaria p.) and its potential as a neuroprotective agent in multiple sclerosis (MS). eighty-eight adult Swiss mice were divided into four male and four female groups, including a control group (distilled water), Palmaria p.-treated group (600 mg/kg b.w.), cuprizone (CPZ)-treated group (mixed chow 0.2%), and a group treated with both CPZ and Palmaria p. The experiment continued for seven weeks. CPZ treatment terminated at the end of the 5th week, with half of the mice sacrificed to assess the demyelination stage. To examine the spontaneous recovery, the rest of the mice continued until the end of week seven. Behavioral (grip strength (GS) and open field tests (OFT)), microbiome, and histological assessments for general morphology of corpus callous (CC) were all conducted at the end of week five and week 7. Palmaria p. can potentially protect against CPZ-induced MS with variable degrees in male and female Swiss mice. This protection was demonstrated through three key findings: (1) increased F/B ratio and expansion of the beneficial Lactobacillus, Proteobacteria, and Bactriodia communities. (2) Protection against the decline in GS induced by CPZ and prevented CPZ-induced anxiety in OFT. (3) Preservation of structural integrity. Because of its propensity to promote microbiota alterations, its antioxidant activity, and its content of -3 fatty acids, Palmaria p. could be a promising option for MS patients and could be beneficial as a potential probiotic for the at-risk groups as a preventive measure against MS.

Fermented milk supplemented with water-soluble curcumin ameliorates survival rate, selected biochemical parameters and fecal microbiota of Ehrlich ascites carcinoma-bearing mice

This study assessed the impact of fermented cow and soy milk supplemented with curcumin on enhancement the health status of female Swiss mice under Ehrlich ascites carcinoma (EAC) condition. Both types of milk were fermented by Lactobacillus plantarum EMCC 1027. Ninety-five grams of basal diet mixed with five grams of either fermented cow or soy milk supplemented with curcumin. Induction of Ehrlich tumor-bearing mice synergized by intraperitoneal injection with 1 × 106 Ehrlich ascites tumor cells after one week of the adaptation period. Our results showed that levels of survival rate were increased to 117% in mice that were fed fermented cow and soy milk while supplementation of fermented soy milk with curcumin improved the survival rate to 150%. The concentration of glutathione and superoxide dismutase in Ehrlich tumor-bearing was increased after feeding with both types of fermented milk. Fermented soy milk supplemented with curcumin showed the highest reduction levels of plasma tumor necrosis factor (TNF)-α and interleukin-6. The relative gene expression TNF-α was also significantly (P < 0.05) down-regulated in mice that were fed fermented soy milk with curcumin. The viable count of lactobacilli and bifidobacteria in feces samples was increased when mice fed both types of fermented milk. Dietary feeding with fermented cow or soy milk supplemented with curcumin has an ameliorative impact on the survival rate, antioxidant capacity, inflammation, fecal microbiota in EAC mouse model. Further research is still needed to investigate the molecular mechanisms in this tumor.

Spermidine prevents the reinstatement of alcohol conditioned place preference

This study investigates whether spermidine (SPD), an endogenous polyamine, alters extinction and reinstatement of alcohol-induced conditioned place preference (CPP) in adult female Swiss mice. CPP was induced by injecting alcohol (1.8 g/kg, i.p.) and placing the animals in the drug-associated compartment for 10 min in four alternate days. During extinction, animals received vehicle or SPD (3, 10 or 30 mg/kg), and were placed in the drug-associated compartment for 10 min in 4 alternate days. Alcohol re-exposure was performed in the alcohol-paired compartment. In a second experiment, after conditioning, animals received vehicle, the N-methyl-d-aspartate (NMDA) receptor polyamine binding site antagonist arcaine (ARC, 0.1 mg/kg), SPD (10 mg/kg) or the association of both (ARC+SDP) in the drug-associated compartment. Animals were then sequentially subjected to alcohol re-exposure and a post-reexposure test. Spermidine did not alter CPP extinction, but prevented the reinstatement of CPP induced by alcohol reexposure. Arcaine prevented the effect of spermidine on alcohol-induced CPP reinstatement. The results suggest that SPD may facilitate the reconsolidation of conditioning memory, disrupting CPP. This effect seems to involve the polyamine binding site at the NMDA receptor, because it is prevented by ARC.

Maternal chronic caffeine intake impairs fertility, placental vascularization and fetal development in mice

Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake and the effects on fetal growth. Female Swiss mice received, via gavage, caffeine doses (either 60, 120 or 240 mg/kg/day) seven days before mating until gestational days-(GD) 11.5 or 17.5. Fetal biometrical parameters were assessed, and placentae were either submitted to histomorphometrical or molecular evaluation of angiogenesis (placental growth factor-1[PlGF-1]), apoptosis (Caspase-3) and proliferation (Ki-67) markers (evaluated in Swiss dams) and to intravital microscopy (evaluated in C57BL/6 dams). Caffeine exposed fetuses exhibited intrauterine growth restriction in a sex-dependent manner, with greater commitment of female fetuses (P < 0.05). In addition, placentae from dams that received 120 mg/kg/day showed less irrigation by maternal blood and greater development of fetal vasculature, characterized by higher number of larger vessels (P < 0.05). Although no effects on apoptosis (Caspase-3) and angiogenesis (PlGF-1) were observed, dams treated with 60 mg/kg/day showed greater placental cell proliferation (Ki-67 staining) at GD 11.5 (P < 0.05). The group treated with 240 mg/kg/day exhibited only one pregnant dam for each gestational age, suggesting that this high caffeine consumption may compromise fertility. Taken together, even in the doses currently ingested by many pregnant women, caffeine has detrimental effects on placental vasculature and fetal development in mice. Therefore, our results strongly suggest that caffeine consumption in human pregnancies greater than the recommended doses should be avoided.

Exploring cardiac impact of oral nicotine exposure in a transplantable Neoplasm Mice Model: Insights from biochemical analysis, morphometry, and molecular docking: Chlorella vulgaris green algae support

Nicotine-induced cardiac tissue damage is a concern for cancer patients, but the exact pathogenesis from nicotine oral exposure is unclear. This study was designed to investigate the impact of nicotine and Chlorella vulgaris (Ch. V) on cardiac glutathione homeostasis, inflammatory response, cardiac damage markers, apoptotic proteins and histopathological findings in an experimentally transplantable neoplasm mouse model (Ehrlich ascites carcinoma; EAC). In the in-vivo experiment, the female Swiss mice were divided into four groups: control, Ch.V (100 mg/kg), Nicotine (100 µg/ml/kg), and a combination group ( Nocotine+ Ch.V) for 40 days. Furthermore, in this study,the effects of C. vulgaris components on caspase-3, TNF-α, and IL-1β activity were explored using Molecular Operating Environment (MOE) docking software to ensure its ability to counteract the toxic effects of nicotine. The results indicated that nicotine has induced significant (P < 0.001) cardiopathic alterations in EAC-bearing mice with changes in cardiac tissue enzymes. C. Vulgaris attenuated the nicotine-induced cardiac glutathione inhibition, suppressed the inflammatory response, exerted antiapoptotic effects, mitigated myocardial injury biomarkers, and repaired cellular and tissue damage. Moreover, the molecular docking results revealed the ability of C. vulgaris to bind with interleukin-1 receptor type 1 (IL1R1) and tumor necrosis factor receptor superfamily member 1 A (TNFRSF1A) in the mice tissues, ameliorating apoptosis and inflammatory processes associated with nicotine-induced cardiotoxicity. This study provides a model for understanding nicotine-induced myocardial injury during experimentally transplantable neoplasm. It highlights C. vulgaris as a beneficial food supplement for cancer patients exposed to nicotine orally.

The Antinociceptive Responses of MTDZ to Paclitaxel-Induced Peripheral Neuropathy and Acute Nociception in Mice: Behavioral, Pharmacological, and Biochemical Approaches.

The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca2+-ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mice without affecting locomotion or exploration. MTDZ also modulated multiple pathways, including glutamatergic, NO/L-arginine/cGMP, serotonergic (5-HT1A/1B), opioid, and TRPV1 pathways. Additionally, MTDZ reduced NOx levels and modulated Ca2+-ATPase activity. In conclusion, MTDZ effectively alleviated PTX-induced peripheral neuropathy and demonstrated multi-targeted modulation of pain-related pathways. Its ability to modulate multiple pathways, reduce NOx levels, and modulate Ca2+-ATPase activity makes it a potential pharmacological candidate for peripheral neuropathy, acute nociceptive, and inflammatory conditions. Further research is needed to explore its therapeutic potential in these areas.

The Immunomodulatory Activity of Punica granatum L. Peel Extract Increases the Lifespan of Mice with Lethal Sepsis.

Sepsis is an organ dysfunction syndrome associated with high mortality. To date, no effective treatment is available to combat this disease. Punica granatum L. is a potential alternative treatment due to its anti-inflammatory, antimicrobial, and antioxidant properties. Thus, this study aimed to evaluate the effects of a hydroalcoholic crude extract from the peels of P. granatum (HCEPg) in mice with lethal sepsis. Lethal polymicrobial sepsis was induced in female Swiss mice via cecal ligation and puncture (CLP). Initially, the animals were divided into three groups: Sham (false-operated), CLP-control (phosphate-buffered saline), and CLP-HCEPg (single dose, 5 mg/kg, subcutaneous administration). Treatment was initiated immediately after the induction of sepsis, and survival was evaluated every 12 hr for 5 days. Those who survived were euthanized. Serum cytokine levels were measured using a cytometric bead array Mouse Inflammatory Cytokine Kit. The number of colony-forming units, as well as the number of cells in the lymphoid organs and their activation markers, were analyzed. Results showed that treatment with HCEPg increased lifespan and reduced bacterial counts in the peritoneum, bloodstream, and spleen. HCEPg also decreased hydrogen peroxide secretion by phagocytes and augmented serum IL-10 levels, indicating its systemic anti-inflammatory effects. Additionally, treatment with HCEPg attenuated infection-induced lung hemorrhage. Overall, P. granatum extract improved the lifespan of septic mice, possibly due to its antimicrobial, anti-inflammatory, and immunomodulatory effects, thereby regulating bacterial load and translocation, as well as controlling the systemic inflammation induced by sepsis.

Evaluation of 28-day repeated doses oral toxicity of essential oil from Psidium glaziovianum Kiaersk leaves on various biological parameters in Swiss mice

ABSTRACT Only a small number of the many medicinally important species in the genus Psidium L. have had their safety assessed. Psidium glaziovianum, a plant native to Brazil, is reported to exert antinociceptive and anti-inflammatory effects; however, there are no apparent reports of long-term safety following administering of repeated doses. The aim of this study was to examine the effects of 28-day oral of treatment at 250, 500 or 1,000 mg/kg Psidium glaziovianum essential oil (PgEO) on behavioral and physiological parameters in male and female Swiss mice. First, PgEO was chemically characterized by gas chromatography mass spectrometry (GC-MS). The following parameters were examined: motor activity, body temperature, blood glucose, urine, hematology, biochemistry, histology, and oxidative stress. Characterization of PgEO revealed 48 components which were dominated by sesquiterpenes 1,8-cineol (24.29%), α-pinene (19.73%) and β-pinene (17.31%). Data showed that PgEO treatment in mice increased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) without markedly affecting body weight, hematological or biochemical parameters, as well as water or food consumption. Administration of PgEO in repeated daily dosages over 28 days did not significantly alter exploratory or locomotor activities. Based upon our findings, PgEO administration daily for 28 days, exhibited low toxicity and absence of effects on the nervous system. Data demonstrated that PgEO produced hypoglycemic and antioxidant actions which need to be considered in safety assessment.

Rosuvastatin enhances alterations caused by Toxoplasma gondii in the duodenum of mice

Infection by Toxoplasma gondii may compromise the intestinal histoarchitecture through the tissue reaction triggered by the parasite. Thus, this study evaluated whether treatment with rosuvastatin modifies duodenal changes caused by the chronic infection induced by cysts of T. gondii. For this, female Swiss mice were distributed into infected and treated group (ITG), infected group (IG), group treated with 40 mg/kg rosuvastatin (TG) and control group (CG). After 72 days of infection, the animals were euthanized, the duodenum was collected and processed for histopathological analysis. We observed an increase in immune cell infiltration in the IG, TG and ITG groups, with injury to the Brunner glands. The infection led to a reduction in collagen fibers and mast cells. Infected and treated animals showed an increase in collagen fibers, acidic mucin-producing goblet cells, intraepithelial lymphocytes and mast cells, in addition to the reduction of muscle, neutral mucin-producing and Paneth cells. While treatment with rosuvastatin alone led to increased muscle layer, proportion of neutral mucin-producing goblet cells, Paneth cells, and reduction of collagen fibers. These findings indicate that the infection and treatment caused changes in the homeostasis of the intestinal wall and treatment with rosuvastatin potentiated most parameters indicative of inflammation.