Intraperitoneal Route Research Articles

Effect of cilnidipine on depression-like behaviour in male Swiss mice: A study using the tail suspension test

Objective: The objective is to evaluate cilnidipine and compare it with fluoxetine on the depression model in male Swiss mice, utilising the tail suspension test and locomotor activity test. Materials and Methods: The animals were categorised into four groups, each consisting of six individuals (n = 6 per group). The subjects were given the test drug doses of cilnidipine at 5 mg/kg and 10 mg/kg, as well as fluoxetine at 10 mg/kg, for a duration of 21 days through an intraperitoneal route. On days 1, 14 and 21, the locomotor activity was assessed using the actophotometer, while the antidepressant activity was assessed using the tail suspension test (TST). The duration of immobility was assessed using the total sleep time method for a 5-minute period, while the number of counts was monitored for 10 min using an actophotometer. Results: Cilnidipine at a dosage of 10 mg/kg demonstrates a reduction in symptoms of depression when compared to the standard control. Neither cilnidipine 5 mg/kg nor 10 mg/kg resulted in a noteworthy decrease in locomotor activity. Conclusion: The present study demonstrated a substantial antidepressant effect of cilnidipine 10 mg/kg dosage. More research is needed to validate the results reported.

Effects of Nickel Bioaccumulation on Hematological, Biochemical, Immune Responses, Neuroinflammatory, Oxidative Stress Parameters, and Neurotoxicity in Rats.

Nickel (Ni) exposure is linked to numerous health issues, including dermatitis, immunotoxicity, and cancer. Emerging evidence suggests Ni may cross the blood-brain barrier, accumulating in the brain and causing neuroinflammation, oxidative stress, and neuronal apoptosis. Herein, we investigated the effect of Ni exposure through the intraperitoneal route, studying the Ni effect in subacute and chronic toxicity, on various health parameters in Wistar rats. Rats were randomly divided into four groups (n = 10 per group): two groups received a daily intraperitoneal injection of NiCl₂ at a dose of 0.25mg/kg for subacute (21days) or chronic (60days) exposure periods, while the other two groups were treated with NaCl solution (0.9%) as a control for equivalent durations. The study assessed behavioral, biochemical, hematological, immunological, neurobiochemical, and histopathological effects over 21 and 60days. Neurobehavioral tests, blood and tissue analyses, and organ examinations were conducted. This study demonstrates that Ni bioaccumulation in subacute and chronic exposure has significant health impacts in Wistar rats, including hematological, immunological, biochemical, AchE activity, neuroinflammatory, oxidative stress, and neurobehavioral changes. Chronic exposure results in higher Ni accumulation, particularly in the brain, causing neurotoxicity, inflammation, and behavioral disorders such as anxiety, depression, and memory impairment. The findings highlight the importance of limiting Ni exposure to prevent adverse health effects.

Methyl donor ameliorates CCl4-induced liver fibrosis by inhibiting inflammation, and fibrosis through the downregulation of EGFR and DNMT-1 expression.

Methyl donors regulate the one-carbon metabolism and have significant potential to reduce oxidative stress and inflammation. Therefore, this study aims to investigate the protective effect of methyl donors against CCl4-induced liver fibrosis. Liver fibrosis was induced in male Sprague Dawley rats using CCl4 at a dose of 1ml/kg (twice a week for a 4-week, via intraperitoneal route). Subsequently, methyl donor treatments were given orally for the next six weeks while continuing CCl4 administration. After 10 weeks, biochemical, histopathology, immunohistochemistry, western blotting, and qRT-PCR were performed. Methyl donor treatment significantly ameliorated ALT, AST, ALP levels, and oxidative stress associated with CCl4-induced liver injury. The histopathological investigation also demonstrated the hepatoprotective effect of methyl donors against CCl4-induced liver fibrosis, showing reduced tissue damage, collagen deposition, and attenuating the expression of the COL1A1 gene. Further, methyl donors inhibited the CCl4-induced increase in DNMT-1 and NF-κB p65 expression with an upregulation of AMPK. Methyl donor downregulated the CCl4-induced increase in inflammatory and fibrosis related gene expression and inhibited the apoptosis with a downregulation of EGFR expression. Here, we provide the first evidence that methyl donor combinations prevent liver fibrosis by attenuating oxidative stress, inflammation, and fibrosis through DNMT-1 and EGFR downregulation.

Mechanisms of Apoptosis and Pulmonary Fibrosis Resulting From Sulfur Mustard-Induced Acute Pulmonary Injury in Rats.

Sulfur mustard (SM) is a highly toxic bifunctional alkylating agent that inflicts severe damage on the respiratory tract. Although numerous studies have examined the mechanisms underlying SM-induced pulmonary injury, the exact pathways involved remain unclear. This study aims to investigate an acute pulmonary injury model, with SM administered as a single intraperitoneal injection (8mg/kg) or single intratracheal instillation (2mg/kg) at equal toxicity doses (1LD50). The results revealed that epithelial cells in the alveolar septa of the intraperitoneal SM group exhibited a significantly higher expression of apoptotic markers, including pro-apoptotic protein Bax, caspase-3, and caspase-9 proteins, than those in the tracheal SM group. Conversely, the expression of the anti-apoptotic protein Bcl-2 was significantly lower in the intraperitoneal SM group than in the tracheal SM group, as confirmed by TUNEL staining and immunohistochemical staining. The intraperitoneal SM group exhibited markedly higher expression of fibrosis-related proteins, including MMP-2, MMP-9, TIMP-1, TIMP-2, collagen type I, collagen type III, TGF-β1, and Smad7, than the tracheal SM group. These markers, detected through immunohistochemical immunolabeling, indicate a more significant fibrotic response in the intraperitoneal group. In summary, this study demonstrates that intraperitoneal exposure to SM results in increased apoptosis, elevated expression of pro-apoptotic proteins, and fibrosis-related proteins in the alveolar epithelial cells compared with intratracheal exposure, even at equivalent toxicity levels. Our findings highlight the suitability of the intraperitoneal route for further investigation and identify apoptotic and fibrosis-related proteins as potential targets for intervention in SM-induced pulmonary injury.

Emoquine-1: A Hybrid Molecule Efficient against Multidrug-Resistant Plasmodium Parasites, Including the Artemisinin-Resistant Quiescent Stage, and Also Active In Vivo.

To challenge the multidrug resistance of Plasmodium falciparum malaria parasites, new hybrid compounds were synthesized and evaluated against laboratory strains and multidrug-resistant clinical isolates. Among these hybrids, emoquine-1 was the most active on proliferative P. falciparum, with IC50 values in the range of 20-55 nM and a high selectivity index with respect to mammalian cells. This drug retained its activity on several multiresistant field isolates from Cambodia and Guiana, exhibited no cross-resistance to artemisinin, and is also very active against the quiescent stage of the artemisinin-resistant parasites, three features that constitute the gold standard for new antimalarial drugs. In vivo, emoquine-1 is active against Plasmodium vinckei petteri at 25 mg/kg/d per os and by the intraperitoneal route at 1-5 mg/kg/d, with total cure at 10 mg/kg/d, making emoquine-1 an ideal candidate to fight Plasmodium parasites resistant to artemisinin-based combination therapies (ACTs) with a capacity to eliminate persistent parasites.

Brucella suis ΔmapB outer membrane vesicles as an acellular vaccine against systemic and mucosal B. suis infection.

Swine brucellosis, caused by Brucella suis, is a worldwide infectious zoonotic disease. Currently, there are no available human or porcine vaccines to protect against B. suis infection, which is primarily acquired through the mucosa. We recently described B. suis MapB, the homologous protein of TamB, the inner membrane component of the TAM system. Our findings indicate that MapB is involved in bacterial cell envelope homeostasis. In this study, we characterize the outer membrane vesicles (OMVs) of B. suis 1330 (wt) and those of B. suis ΔmapB (ΔmapB) mutant strain and evaluate their vaccine potential in mice. OMVs were isolated using the ultracentrifugation method and characterized through electron microscopy, Dynamic Light Scattering, SDS-PAGE and proteomics. Immunogenicity was assessed by intramuscular immunization of mice with wt OMVs or ΔmapB OMVs, followed by the measurement of antigen-specific antibody levels and functional assays to evaluate the protective capacity of the antibodies. Cellular immunity was assessed by characterizing cytokine secretion through ELISA after in vitro stimulation of spleen cells with heat-killed B. suis. To determine the level of protection conferred by immunization, mice were challenged with virulent B. suis via intraperitoneal or intratracheal routes, and the bacterial load was quantified post-challenge. Dynamic Light Scattering of the OMVs from both strains revealed the presence of spherical structures of 90-130 nm. Proteomic analysis identified 94 and 95 proteins in the wt and ΔmapB OMVs, respectively, including several known Brucella immunogens. Both OMVs showed immunoreactivity with sera from Brucella-infected pigs. Intramuscular immunization of mice with both OMVs induced antigen-specific IgG in serum, with the ΔmapB OMVs group showing higher titers compared to the wt OMVs group. Serum antibodies from both OMVs groups reduced B. suis adherence and invasion of lung epithelial cells and enhanced its phagocytosis by macrophages. Upon in vitro antigen stimulation, spleen cells from mice immunized with ΔmapB OMVs secreted higher levels of interleukin-17 and especially gamma interferon compared to cells from mice immunized with wt OMVs, suggesting the induction of a stronger T helper 1 response in the ΔmapB OMVs group. While immunization with both wt and ΔmapB OMVs achieved the same level of protection following intratracheal infection with B. suis (p<0.01), immunization with ΔmapB OMVs provided higher levels of protection against intraperitoneal infection. Overall, these results demonstrate that the B. suis ΔmapB OMVs are immunogenic and capable of inducing both cellular and humoral immune responses that protect against mucosal and systemic B. suis challenges.

Intraperitoneal versus intravenous administration of Flamma®-conjugated PEG-alendronate-coated upconversion nanoparticles in a mouse pancreatic cancer model.

Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma® fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma® as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma® nanoparticles are thus promising for new treatment avenues for pancreatic cancer.

Theoretical determination of the biological activities of some benzimidazolederivative compounds with potential as active pharmaceutical agents

The biological activities of twelve different benzimidazole derivative compounds synthesized and registered in the literature were theoretically calculated with Way2Drug PASS software. Seven different biological activities, including acute rat toxicity, adverse drug effects, antibacterial activity, antifungal activity, anti-HIV activity, antiviral activity, and cell line cytotoxicity, were calculated for each benzimidazole derivative compound examined here. Rat acute toxicity was calculated in four different ways. These are Rat IP (intraperitoneal administration route) LD50, Rat IV (intravenous administration route) LD50, Rat Oral (oral administration route) LD50, and Rat SC (subcutaneous administration route) LD50. According to the results, a classification was also made for each method. Adverse effects that the molecules may show were determined with the help of the calculated Pa (probability of activity) and Pi (probability of inactivity) values. The antibacterial effect of each molecule against which bacteria was determined and the confidence value of this effect was calculated. Likewise, it was determined whether the molecules showed antifungal properties. It was determined against which fungus the molecules showing antifungal properties showed this effect, and the confidence value was calculated. The anti-HIV properties of the molecules were studied for five different targets (protease (HIV-1), reverse transcriptase (HIV-1), integrase (HIV-1), REV (regulator of virion) (HIV-1), and TAT (trans-activator of transcription) (HIV-1)) and the p function of the IC50 (half maximal inhibitory concentration) values obtained were analyzed. Anti-viral effects of molecules examined. Here, the viruses against which they show this effect were determined, and the confidence value was calculated together with the target protein. Finally, cancer cell line and non-tumor cell line properties of the molecules were determined by Pa and Pi values as well as tissue and tumor type.

Investigation of the Effects of Fosfomycin in Kidney Damage Caused by CLP-Induced Sepsis.

Sepsis, a life-threatening condition characterized by dysregulated host responses to infection, often leads to multi-organ dysfunction, including kidney injury. Kidney damage in sepsis can have severe consequences and is associated with high mortality rates. This study aimed to investigate the potential therapeutic effects of fosfomycin (FOS), a broad-spectrum antibiotic with immunomodulatory properties, on kidney damage induced by cecal ligation and puncture (CLP)-induced sepsis in a rodent model. In total, 24 rats were randomly divided into three groups. Group 1 (n = 8), the healthy control group (C), received a single dose of 0.9% NaCl (saline) solution via an intraperitoneal (i.p.) route. To group 2 (n = 8), the CLP group, CLP-induced sepsis was applied without medication, and a single dose of 0.9% NaCl (saline) solution was applied i.p. before induction. To group 3 (n = 8), the CLP + FOS (500 mg/kg) group, a single dose of 500 mg/kg FOS was administered i.p. before sepsis induction. The effects of fosfomycin on kidney function, histopathological changes, inflammatory markers, oxidative stress, and apoptosis were assessed. In the fosfomycin-treated group, the histological analysis results demonstrated reduction in kidney tissue damage and inflammation. Additionally, fosfomycin attenuated the upregulation of pro-inflammatory cytokines and reduced oxidative stress markers in kidney tissue. Furthermore, fosfomycin treatment was associated with a decrease in apoptotic cell death in the kidney. These findings suggest that fosfomycin may have a protective effect on kidney damage caused by CLP-induced sepsis. The potential mechanisms underlying this protection include the modulation of inflammation, reduction of oxidative stress, and inhibition of apoptosis.

Metabolomic Profile Modification in the Cerebellum of Mice Repeatedly Exposed to Khat and Treated with β-Lactamase Inhibitor, Clavulanic Acid.

Catha edulis, commonly known as khat, is used for its psychoactive effects and is considered a natural amphetamine. The current study investigated the metabolomic profile in the cerebellum of mice after repeated exposure to khat and evaluated the effects of clavulanic acid on the metabolomic profile in the cerebellum in khat-treated mice. Male C67BL/6 mice that were 6-9 weeks old were recruited and divided into three groups: the control group was treated with 0.9% normal saline for 17 days; the khat group was given khat extract at a dose of 360 mg/kg via the intraperitoneal (i.p) route for 17 days; and another khat group was treated with khat for 17 days and clavulanic acid at a dose of 5 mg/kg for the last 7 days (days 11-17). At the end of the 17th day, the animals were sacrificed, and their brains were immediately collected and stored at -80 °C. The cerebellum region of the brain was isolated in each group by micropuncture using cryostat and underwent a metabolomics study via Gas Chromatography/Mass Spectroscopy (GC/MS). The total peak area ratios of the selected metabolites in the cerebellum after repeated exposure to the khat extract were significantly reduced (p < 0.05) and treatment of the khat group with clavulanic acid significantly increased (all p < 0.05) the total peak areas ratios of the selected metabolites when compared to their corresponding areas in the alternative khat group. These levels of selected metabolites were further confirmed by observing the metabolite peak area ratios and performing a heat map analysis and a principal compartment analysis of the samples in the cerebellum. A network analysis of altered metabolites in the cerebellum showed a strong correlation between the different metabolites, which showed that an increase in one metabolite can modulate the levels of others. An analysis using the MetaboAnalyst software revealed the involvement of selected altered metabolites like lactic acid in many signaling pathways, like gluconeogenesis, while enrichment analysis data showed altered pathways for pyruvate metabolism and disease pathogenesis. Finally, a network analysis showed that selected metabolites were linked with other metabolites, indicating drug-drug interactions. The present study showed that repeated exposure of mice to khat altered the levels of various metabolites in the cerebellum which are involved in the pathogenesis of different diseases, signaling pathways, and interactions with the pharmacokinetic profile of other therapeutic drugs. The treatment of khat-treated mice with clavulanic acid positively modified the metabolomics profile in the cerebellum and increased the levels of the altered metabolites.

Small Molecule Myeloperoxidase (MPO) Inhibition Prevents Delayed Cerebral Injury (DCI) After Subarachnoid Hemorrhage (SAH) in a Murine Model.

Delayed cerebral injury (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is a preventable injury that would improve patient outcomes if an effective treatment can be developed. The most common long-term disability in patients with SAH is cognitive dysfunction. Contrary to the common theory that damage from DCI originates solely from ischemia caused by cerebral vasospasm, inflammation has been shown to be an important independent mediator of DCI. Neutrophil infiltration of the meninges is a critical step in developing late spatial memory deficits in a murine model of SAH and may serve as a surrogate marker for disease progression. Importantly, myeloperoxidase (MPO) null mice do not develop meningeal neutrophilia and are protected from spatial memory deficits. In this study, wildtype mice administered a single dose of the MPO inhibitor (MPOi) AZD5904 at peak neutrophil entry day have a higher percentage of neutrophils that remain in the meningeal blood vessel 6days after the hemorrhage suggesting neutrophil extravasation into the meninges is inhibited (79 ± 20 vs. 28 ± 24, p < 0.01). Interestingly, the intraperitoneal route of administration has a larger effect than the intrathecal route suggesting that MPO inhibition is best administered systemically not in the central nervous system. Second, mice administered AZD5904 intraperitoneal for 4 consecutive days starting 2days after the hemorrhage do not develop delayed spatial memory dysfunction (two-way analysis of variance, p > 0.001 F [2, 22] = 10.11). Systemic MPOi prevents neutrophil entry into the meninges and prevents spatial memory dysfunction. MPOi is a promising strategy for translation to patients with aneurysmal SAH.

Mastoid approach for local drug delivery to the inner ear for treating hearing loss

Hearing loss is a prevalent disability worldwide. Dexamethasone (Dex) is commonly used to treat hearing loss, administered either systemically or locally. However, targeted delivery of Dex to the inner ear remains challenging, which limits its therapeutic efficacy. This study aimed to develop new methods to improve Dex delivery to the inner ear and enhance its treatment effect. Mastoid, intraperitoneal, and intratympanic delivery routes for Dex were investigated in guinea pig cochlea. Liquid chromatography-mass spectrometry and immunohistochemistry were employed to compare the distribution of Dex in the perilymph and tissue uptake. Poly (lactic-co-glycolic acid) nanoparticles loaded with Dex (PLGA-NPs-Dex) were prepared, and their transport mechanism across the round window membrane (RWM) was explored. Among the three delivery routes, mastoid administration produced the highest Dex concentration in the perilymph. Compared to the control, PLGA-NPs-Dex provided significantly enhanced protection against lipopolysaccharide- and noise-induced hearing damage following mastoid administration. Mastoid delivery provides an accessible route for drug delivery to the inner ear and nanoparticle-based systems via this route represent a viable strategy for treating inner ear diseases. This approach caused less damage to the inner ear, making it a promising option for clinical use in treating hearing loss.

Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal metastasis.

This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.

Study of the Acute Toxicity of an Aqueous Extract of the Leaves of Senna alata (L.) ROXB (Caesalpiniaceae) to Mammals

Senna alata (L.) ROXB (Caesalpiniaceae) is a plant known and appreciated by the Ivorian population. It is commonly used to treat high blood pressure and constipation. The aim of this study was to investigate the acute toxicity of the aqueous extract of leaves of Senna alata leaves (EAqSa) in mammals. To do this, a phytochemical study of this extract was carried out. Acute toxicity was assessed by the intraperitoneal and oral routes. The oral toxicity tests were carried out in accordance with directive 423 of the Organisation for Economic Co-operation and Development (OECD) using three (3) lots of three (3) rats, one control lot and two (2) test lots. The control lot received 2 ml of distilled water, one test lot received 2000 mg/ kg bw of EAqSa and the second test lot received 5000 mg/ kg bw of the extract in a single dose. Toxicity tests by intraperitoneal administration are carried out using six (6) lots of six (6) mices including a control lot receiving 0.5 ml of EAqSa. The five (5) test lots received 0.5 ml of doses ranging from 750 to 2000 mg/kg bw of the extract. The animals from the different test lots were observed for twenty-four (24) hours. Qualitative phytochemical analysis revealed the presence of polyphenols, sterols and polyterpenes, flavonoids, catechic tannins, saponosides, quinonic compounds and alkaloids. Acute toxicity tests show that this extract is only slightly toxic by the intraperitoneal route and non-toxic by the oral route. The oral route of administration would be the most recommended for the pharmacological use of this extract, but should be used in moderation.

Cyclophosphamide-induced multiple organ dysfunctions: unravelling of dose dependent toxic impact on biochemistry and histology.

Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated. This study aimed to investigate dose dependent toxic impact of cyclophosphamide on liver, kidney, brain and testis emphasizing serum and tissue biochemical and histological alterations. Experimental design consisted of five groups of albino rats. Group 1-5 were administered vehicle for five consecutive days. On 6th day, group 1 received vehicle only and termed as control; group 2-5 received cyclophosphamide through intraperitoneal route at the rate of 50, 100, 150 and 200mg/kg dose, respectively. After 24h of the last administration, rats were euthanised; serum and tissue biochemistry; histology, sperm count and its motility were performed. Serological, biochemical and histological indices exhibited dose dependent deviations from their regular status as a marker of toxicity in liver, kidney, brain and testis. Tukey's HSD post hoc test revealed maximum damage in multiple organs with 200mg/kg dose of cyclophosphamide.

Fingolimod, a sphingosine-1-phosphate receptor modulator, prevents neonatal bronchopulmonary dysplasia and subsequent airway remodeling in a murine model.

Neonatal bronchopulmonary dysplasia (BPD) is associated with alveolar simplification and airway remodeling. Airway remodeling leads to deformation of airways characterized by peribronchial collagen deposition and hypertrophy of airway smooth muscle, which contribute to the narrowing of airways. Poorly developed lungs contribute to reduced lung function that deteriorates with the passage of time. We have earlier shown that sphingosine kinase 1 (SPHK 1)/sphingosine-1-phosphate (S1P)/S1P receptor1 (S1PR1) signaling plays a role in the pathogenesis of BPD. In this study, we investigated the role of fingolimod or FTY720, a known S1PR1 modulator approved for the treatment of multiple sclerosis in the treatment of BPD. Fingolimod promotes the degradation of S1PR1 by preventing its recycling, thus serving as the equivalent of an inhibitor. Exposure of neonatal mice to hyperoxia enhanced the expression of S1PR1 in both airways and alveoli as compared with normoxia. This increased expression of S1PR1 in the airways persisted into adulthood, accompanied by airway remodeling and airway hyperreactivity (AHR) after neonatal hyperoxia. Intranasal fingolimod at a much lower dose compared with the intraperitoneal route of administration during neonatal hyperoxia improved alveolarization in neonates and reduced airway remodeling and AHR in adult mice associated with improved lung function. The intranasal route was not associated with the lymphopenia seen with the intraperitoneal route of administration of the drug. An increase in S1PR1 expression in the airways was associated with an increase in the expression of enzyme lysyl oxidase (LOX) in the airways following hyperoxia, which was suppressed by fingolimod. This association warrants further investigation.NEW & NOTEWORTHY The role of the S1P receptor1 modulator, fingolimod, as an FDA-approved drug in preventing the recurrence of multiple sclerosis is established. Fingolimod prevented bronchopulmonary dysplasia (BPD) and its sequela of airway remodeling in a neonatal murine model. This protection was associated with the downregulation of lysyl oxidase signaling pathway. Fingolimod could be repurposed for the therapy of BPD.

A Comprehensive Review of the Evaluation of in Situ Gels

In situ gels are now among the most widely used and widely available systems. These systems minimize drug administration frequency because of their special sol-to-gel transition properties, increasing patient comfort. Other benefits of these systems include easy production, improved adherence, and ease of use. 'Sol-gel' produces a colloidal suspension or solution by hydrolyzing the precursor and then polymerizing it through condensation. These in situ gelling techniques gel at the accomplishment site because they can be administered as solutions. Recently, several researchers developed liposomes, microspheres, nanoemulsions, nanospheres, and other in situ gelling systems. One of the greatest innovative drug delivery methods to date is the "in situ gel" system, which promotes better patient comfort and compliance as well as a prolonged and regulated release of the medication. With in situ gel formation, a variety of natural and synthetic polymers may find application in oral, ophthalmic, transdermal, buccal, intraperitoneal, parenteral, injectable, rectal, and vaginal routes. Research on the in-situ gel system has a lot of potential to offer cutting-edge methods for medication delivery systems.

A Review on In Vivo Research Dehydration Models and Application of Rehydration Strategies

Background: Dehydration, a common condition where the amount water lost from the body exceeds intake, disrupts metabolic processes and negatively impacts health and performance. Rehydration, the process of restoring body fluids and electrolytes to normal levels, is crucial for maintaining physiological health. In vivo dehydration models are experimental systems used to study the effects of dehydration on living organisms. However, a comprehensive summary of in vivo models and the application of human rehydration strategies is lacking. Methods: This review provides a comprehensive overview of various in vivo models and rehydration strategies. Results: In vivo models, stimulated by fluid restriction, exercise, thermal exposure, and chemicals, have been used to study dehydration. Importantly, the principles, characteristics, and limitations of the in vivo models are also discussed, along with rehydration administration methods, including oral, intestinal, intravenous, subcutaneous, and intraperitoneal routes. Additionally, rehydration strategies and the application for managing different dehydration conditions both in daily life and clinical settings have been summarized. Conclusions: Overall, this review aims to enhance the understanding of the conditions in which in vivo dehydration models and rehydration strategies are applicable, thereby advancing research into the physiological and pathological mechanisms of dehydration and supporting the development of effective rehydration therapies.

Functional observational battery (FOB) tests using caffeine and chlorpromazine hydrochloride in sprague-dawley rats.

Caffeine is believed to exert its therapeutic effects by acting as a nonselective, competitive antagonist of adenosine receptors. Chlorpromazine, a phenothiazine, is a classic psychotropic mediator extensively used in the clinical administration of psychotic disorders. This study aimed to validate the procedures used for performing Functional Observational Battery (FOB) tests, to demonstrate the proficiency and interobserver reliability during the FOB tests and also to assess effect on neurobehavioral parameters using positive controls in rats. The rats were administered with Caffeine in Milli-Q water as oral gavage at the dose of 20 mg/kg and Chlorpromazine HCl in 0.9% Saline as intraperitoneal route at the dose of 20 mg/kg. No inter-personnel variability was observed in home cage, handling, open field and sensory reactivity observations recorded in Proficiency test. In conclusion, the known effects of positive controls; caffeine and chlorpromazine HCl on neurobehavioral/Functional Observational Battery parameters including autonomic, neuromuscular and sensory reactivity tests were detected in the current study. FOB test procedures for neurobehavioral, grip strength and motor activity are adequate for the detection of neurotoxic effects of positive controls. No major inter-personnel variability was observed between study personnel in neurobehavioural observations.

A murine experimental model of the pulmonary thrombotic effect induced by the venom of the snake Bothrops lanceolatus.

The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved. The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection. An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect.