Immune response, oxidative stress, and histological changes of Wistar rats after being administered with Parascaris equorum antigen.

Worldwide, particularly in developing nations, helminth infections are the leading causes of livestock illness and mortality. Parascaris (P.) equorum, a parasitic worm from the Ascarididae family, significantly impacts the production, health, and working performance of equines. This study aimed to investigate the impact of intraperitoneal sensitization of P. equorum on the immune system, oxidative stress, and histology in Wistar rats. After acclimatization for 7 days, we divided the rats into five groups, each consisting of six rats. Group I, serving as the control, was administered distilled water, followed by groups II (day 7), III (day 14), IV (day 21), and V (day 33). The rats were euthanized every day mentioned (Days 7-33). On day 0, a dosage of 1ml/100 gm rat (containing 500 µg/ml protein content) emulsified crude antigen extract with an incomplete Freund's adjuvant (1:1 volume), followed by a second dose of the same antigen concentration on day 7. To assess the allergenicity of this nematode, we measured a whole blood profile, serum levels of IFN-γ, IL-5, IL-10, IL-13, and IL-33, total immunoglobulins IgE and IgG, and oxidative stress markers. Also, we examined histological changes in the liver, kidney, and spleen. The results showed that values of total leukocyte count, granulocytes, monocytes, and lymphocytes were significantly (P < 0.05) increased on day 14 post-infection relative to other days of investigation. It was found that the levels of total immunoglobulins (IgE and IgG) and cytokines (INF-γ, IL-5, IL-13, and IL-33) on days 14 and 21 were significantly higher than in the control group. At all periods of the experiment, the injected group exhibited significantly higher concentrations of MDA and NO compared to the control group (P < 0.05). Conversely, GSH and CAT levels (P < 0.05) dropped significantly on days 7, 14, and 21. Different rat tissues showed alterations. Ultimately, this study described the detrimental effects of P. equorum crude antigen administration on the immune system, oxidative states, and histological changes of Wistar rats at various intervals.

Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment.

OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.

Anti-inflammatory and anti-oxidant action of tadalafil in testicular regeneration process after heat stress.

Tadalafil, a potent phosphodiesterase inhibitor 5 (PDE-5), is commonly used for the management of erectile dysfunction. However, its therapeutic potential extends beyond this indication. This study aimed to investigate the impact of tadalafil on the recovery of testicular parenchyma in male Wistar rats exposed to testicular thermal stress. Fifty-four Wistar rats were subjected to testicular thermal stress and randomly assigned to receive either tadalafil treatment (TAD) or no treatment (control). TAD was administered intraperitoneally at a dose of either 0.9 mg/kg or 1.8 mg/kg. Biometric parameters, histopathological assessment of the testis, serum testosterone levels, oxidative stress, and interleukin levels were evaluated on days 7, 15, and 30 after thermal shock. The animals were euthanized at the end of each experimental period, and samples were collected. TAD treatment maintained testicular weight and reduced the testicular degenerative process up to day 7 post-injury. However, despite TAD therapy, serum testosterone levels were decreased in the treated groups at days 7 and 15 post-thermal stress. TAD also decreased TNF-α and NO levels at different doses but had no effect on IL-6. The treatment with TAD after heat shock demonstrated anti-inflammatory and antioxidant properties but did not prevent the aggravation of testicular lesions in subsequent periods, even with the systematic reduction in TNF-α and NO levels. Therefore, this selective PDE-5 inhibitor, at the dosages used, did not have a positive impact on testosterone levels during the post-thermal stress period, which could compromise the resumption of the spermatogenic process.

Heparin as a Potential Therapeutic Substance for Post-Traumatic Stress Disorder.

In sexually mature male Wistar rats with modeled post-traumatic stress disorder, personalized characteristics of neurobiological reactions in the population of predator-induced stress-resilient and stress-susceptible heparinized animals were determined. Characteristics of the systemic response of immune mechanisms, hypothalamic-pituitary-adrenal axis, behavioral manifestations, as well as basic properties of the CNS (excitation/inhibition) are presented. The study demonstrated encouraging positive results of the course administration of unfractionated heparin at a dose below the therapeutic and prophylactic doses. The inclusion of heparin drugs into the clinical practice for the treatment of post-traumatic stress disorder will not require large-scale clinical trials, because many effects of heparin as a nonspecific adaptogen are well studied. Moreover, these properties were confirmed at a higher technological level during the COVID-19 pandemic.

Therapeutic potential of silver nanoparticles from Helianthemum lippii extract for mitigating cadmium-induced hepatotoxicity: liver function parameters, oxidative stress, and histopathology in wistar rats.

Introduction: This study explores the therapeutic potential of silver nanoparticles (Ag NPs) synthesized using a Helianthemum lippii extract in mitigating cadmium-induced hepatotoxicity in Wistar rats. Given the increasing environmental and health concerns associated with cadmium exposure, novel and eco-friendly therapeutic strategies are essential. Methods: Ag NPs were characterized using X-ray diffraction, UV-Vis spectrometry, and energy-dispersive X-ray spectroscopy with scanning electron microscopy, confirming their formation with a cubic crystal structure and particle sizes ranging from 4.81 to 12.84 nm. A sub-acute toxicity study of Ag NPs (2 mg/kg and 10 mg/kg) was conducted, showing no significant difference compared to untreated control rats (n = 3 animals/group). Subsequently, adult Wistar rats (n = 5/group) were divided into a control group and three experimental groups: Ag NPs alone, exposure to 50 mg/kg CdCl2 in drinking water for 35 days, and CdCl2 exposure followed by 0.1 mg/kg/day Ag NPs intraperitoneally for 15 days. Results: In the CdCl2-exposed group, there was a significant decrease in body weight and increases in alanine and aspartate transaminase levels (p < 0.05 vs. control), indicating hepatotoxicity. Additionally, antioxidant defenses were decreased, and malondialdehyde levels were elevated. Liver histology revealed portal fibrosis, inflammation, necrosis, sinusoid and hepatic vein dilation, and cytoplasmic vacuolations. Treatment with Ag NPs post-CdCl2 exposure mitigated several adverse effects on liver function and architecture and improved body weight. Discussion: This study demonstrates the efficacy of Ag NPs synthesized via a green method in reducing cadmium-induced liver damage. These findings support the potential of Ag NPs in therapeutic applications and highlight the importance of sustainable and eco-friendly nanoparticle synthesis methods. By addressing both toxicity concerns and therapeutic efficacy, this research aligns with the growing emphasis on environmentally conscious practices in scientific research and healthcare.

Bio distribution and acute toxicity profiling of Pluronic F127 coated Titanium dioxide nanotubes in adult Wistar rats.

Metal and metal oxide nanoparticles are gaining immense attention among researchers owing to their admirable application potentials in various therapeutic events. Titanium dioxide (TiO2) has been recognized as one of the leading candidates in this category and holds wide interest within the scientific community. Among the various morphological nanoforms of TiO2, nanotube is grabbing remarkable attention as they have succeeded as an active vehicle in various medical procedures like intravascular stenting, drug delivery, as biosensors etc. This ultimately demands toxicity profiling of nanotubes in various aspects. Present study elaborates a concept through which acute toxicity profiling of TiO2 nanotubes in adult Wistar rats is presented. TNTs were synthesized via solvo-thermal approach and surface coated with a biocompatible polymer; Pluronic-F127 (P-F127). This step assists in ameliorating the troubles associated with the nanomaterial dispersion stability. The experimental rats were intraperitoneally administered with TNT-P (10 mg/kg) and sacrificed on different time periods (3rd, 7th and 14th days). Biodistribution of the material was tracked in major tissues including brain, liver, spleen and kidneys. A set of acute toxicity studies was performed which comprises hematology evaluation, biochemical studies, antioxidant detection, analysis of urine parameters, immune modulation study and histopathology evaluation. Many of the experiments revealed an unaltered physiological response in rats; except for some biochemical and hematology parameters. Overall study suggests that, TNT-P do not result into a negative response in Wistar rats over 14 days.

Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats.

These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.

Effect of progestin on thyroid function in female Wistar rats.

Introduction: To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Methods: Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Results: Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Discussion: Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Mitigating cyclophosphamide-associated gonadotoxicity in male Wistar rats: exploring the therapeutic potential of hesperidin.

Hesperidin, a bioactive flavanone glycoside prevalent in citrus fruits, with remarkable therapeutic properties stands out as a formidable defender against the debilitating reproductive toxicity associated with Cyclophosphamide (CYP) chemotherapy. This study explores the protective potential of hesperidin (HSP@100 mg/kg b.wt PO daily) against CYP-induced (@ 40 mg/kg b.wt IP once in a week) reproductive toxicity in male Wistar rats as several studies were documented on single dose toxicity of CYP. In this experiment, we chose multidosage drug effects, which are more relevant in chemotherapy. Twenty-four rats were divided into four groups: Group 1 (Control), group 2 (CYP-treated), group 3 (HSP-treated), and group 4 (CYP + HSP-treated) for 28 days. The experimental design included assessments of relative testicular weight, semen analysis, testosterone levels, oxidative stress markers, inflammatory cytokines, gross and histopathological changes, and immunohistochemical evaluation. The results revealed that the administration of CYP led to a significant reduction in testicular weight, sperm count, motility, and testosterone levels, accompanied by increased oxidative stress and inflammatory response. Hesperidin co-administration demonstrated a protective effect by restoring these parameters to near-normal levels. Histopathological analysis revealed improved testicular architecture in the group 4 compared with the group 2. Oxidative stress indices indicated that hesperidin attenuated CYP-induced damage by reducing malondialdehyde levels, enhancing superoxide dismutase activity and maintaining glutathione levels. Similarly, inflammatory cytokine analysis demonstrated anti-inflammatory effects of hesperidin by reducing tumor necrosis factor-alpha (TNF-α) and elevating interleukin-10 (IL-10) levels in the group 4. Immunohistochemical evaluation of nuclear factor-kappa B (NF-κB) revealed increased inflammation in the CYP group, while hesperidin significantly reduced NF-κB expression, suggesting its anti-inflammatory properties.

Anti-inflammatory effect of Faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 in DENV-3-infected Wistar rats.

Background: Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease. Aim: This study aims to investigate the effect of faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3. Methods: A group of 27 male Wistar rats (Rattus norvegicus) aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively. Results: Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The post hoc analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1ß levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed. Conclusion: The stem bark of S. quadrifida shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1ß.

Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats.

This study explored the effect of a toxic metal(oid) mixture (cadmium, lead, arsenic, mercury, chromium, and nickel) on thyroid function in Wistar rats exposed for 28 or 90 days. Dose levels were determined based on prior human-biomonitoring investigation. The experiment included control (male/female rats, 28 and 90 days) and treated groups, reflecting the lower confidence limit of the Benchmark Dose (BMDL) for hormone levels (M1/F1, 28 and 90 days), median concentrations (M2/F2, 28 and 90 days), 95th percentile concentrations (M3/F3, 28 and 90 days) measured in a human study, and reference values for individual metals extracted from the literature (M4/F4, 28 days only). Blood and thyroid gland samples were collected at the experimental termination. Serum TSH, fT3, fT4, T3, and T4 levels were measured, and SPINA-GT and SPINA-GD parameters were calculated. In silico analysis, employing the Comparative Toxicogenomic Database and ToppGene Suite portal, aimed to reveal molecular mechanisms underlying the observed effects. Results showed greater sensitivity in the female rats, with significant effects observed at lower doses. Subacute exposure increased TSH, fT3, and T3 levels in females, while subchronic exposure in males decreased TSH and fT3 levels and increased fT4. Subacute exposure induced changes even at allegedly safe doses, emphasizing potential health risks. Histological abnormalities were observed in all the treated groups. In silico findings suggested that toxic metal exposure contributes to thyroid disorders via oxidative stress, disruption of micronutrients, interference with hormone synthesis, and gene expression dysregulation. These results indicate that seemingly safe doses in single-substance research can adversely affect thyroid structure and function when administered as a mixture. These findings highlight the complex impact of toxic metal exposure on thyroid health, emphasizing that adhering to accepted safety limits for single-substance research fails to account for adverse effects on thyroid structure and function upon exposures to metal mixtures.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Effects of fecal microbiota transplantation on metabolic health of DBA mice.

Introduction: Numerous studies have demonstrated that C57BL/6 mice exhibit superior growth rates and overall growth performance compared to DBA mice. To investigate whether this discrepancy in growth performance is linked to the composition of gut microorganisms, we conducted fecal microbiome transplantation (FMT) experiments. Methods: Specifically, we transplanted fecal fluids from adult C57BL/6 mice, high-fat C57BL/6 mice, and Wistar rats into weaned DBA mice (0.2mL/d), and subsequently analyzed their gut contents and gene expression through 16S rRNA sequencing and transcriptome sequencing. During the test period, C57BL/6 mice and Wistar rats were provided with a normal diet, and high-fat C57BL/6 mice were provided with a high-fat diet. Results: The results of our study revealed that mice receiving FMT from all three donor groups exhibited significantly higher daily weight gain and serum triglyceride (TG) levels compared to mice of CK group. 16S rRNA sequensing unveiled substantial differences in the abundance and function of the gut microbiota between the FMT groups and the CK group. Transcriptome analysis revealed a total of 988 differential genes, consisting of 759 up-regulated genes and 187 down-regulated genes, between the three experimental groups and the CK group. Functional Gene Ontology (GO) annotation suggested that these genes were primarily linked to lipid metabolism, coagulation, and immunity. Pearson correlation analysis was performed on the differential genes and clusters, and it revealed significant correlations, mainly related to processes such as fatty acid metabolism, fat digestion and absorption, and cholesterol metabolism. Discussion: In summary, FMT from dominant strains improved the growth performance of DBA mice, including body weight gain, institutional growth, and immune performance. This change may be due to the increase of probiotic content in the intestinal tract by FMT and subsequent alteration of intestinal gene expression. However, the effects of cross-species fecal transplantation on the intestinal flora and gene expression of recipient mice were not significant.

Ultrasound-guided and 'blind' sciatic nerve injection techniques: Comparison in rat cadavers.

OBJECTIVE: To compare the success rate and extent of sciatic nerve staining with a bupivacaine-dye solution using two injection techniques: 'blind' or ultrasound-guided approach. STUDY DESIGN: Prospective, experimental, randomized, cadaveric study. ANIMALS: Adult female Wistar rat cadavers [n = 24, mass 352 g (323-374)]. METHODS: Each sciatic nerve was randomly allocated to one of two groups: 'blind' (group B) or ultrasound-guided approach (group US) to injection. Following injection of bupivacaine-dye solution (0.1 mL), gross anatomical dissection was performed to visualize nerve staining, categorizing it as either positive or negative. The length of nerve staining was then measured and visual inspection conducted to identify potential nerve damage. Fisher's exact test was used to compare positive or negative nerve staining, and the Wilcoxon signed rank test used to compare the length of nerve staining between groups. RESULTS: In group B, the bupivacaine-dye solution stained 16/24 sciatic nerves (67% success). In group US, staining was successfully observed in all 24 nerves (100% success, p < 0.004). The length of nerve staining [median (interquartile range)] was 2 (2-3) mm in group B and 5 (4-6) mm in group US (p < 0.001). One sciatic nerve in group B had injectate distributed over 16 mm, suggestive of an intraneural injection. No signs of laceration or nerve damage were visible under 6× magnification in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrasound-guided approach for sciatic nerve injection demonstrated a higher success rate with superior injectate distribution when compared with the 'blind' approach. Ultrasound guidance is recommended over a 'blind' approach for sciatic nerve block in rats when possible.

Creating a Reproducible Model of Spinal Cord Injury in Rats: A Contusion Approach.

Spinal cord injury (SCI) is a devastating clinical condition that affects millions of people worldwide. SCI primarily affects males in younger age groups. It is characterized by a complex of neurological dysfunctions that can lead to permanent disability. We describe an adapted technique for SCI, i.e., a contusion model of SCI, in this chapter. This model is widely used to study the pathology of SCI and test potential therapies. The experimental contusion is performed by using a compression device, which allows the creation of a reproducible injury animal model through the definition of specific injury parameters. A detailed methodology has been developed and described here that utilizes a stereotactic frame and impactor to produce reproducible injuries.

Subchronic exposure to fenpyroximate causes multiorgan toxicity in Wistar rats by disrupting lipid profile, inducing oxidative stress and DNA damage.

BACKGROUND: Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells. METHODS: rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues. RESULTS: FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells. CONCLUSION: FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.

Saffron (Crocus sativus L.) extract attenuates chronic scopolamine-induced cognitive impairment, amyloid beta, and neurofibrillary tangles accumulation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Crocus sativus L. known as saffron, is a popular food condiment with a high aroma, deep colour, and long and thick threads (stigmas) cultivated in Iran, Morocco, Spain, Italy, China, Japan, France, Turkey, and India. In 'Ayurveda', saffron is acknowledged for its immunostimulant, aphrodisiac, cardiotonic, liver tonic, nervine tonic, carminative, diaphoretic, diuretic, emmenagogue, galactagogue, febrifuge, sedative, relaxant, and anxiolytic activities. The renowned Persian physician and philosopher, Avicenna, delineated saffron as an antidepressant, hypnotic, anti-inflammatory, hepatoprotective, bronchodilator, and aphrodisiac in his book, the Canon of Medicine. Within traditional Iranian Medicine (TIM), saffron is characterized as a mood elevator and a rejuvenator for the body and senses. Further, the ethnopharmacological evidence indicates that saffron has shown an effect against neurodegenerative disorders namely, dementia, Alzheimer's, and Parkinson's with its bioactive constituents i.e., carotenoids and apocarotenoids. AIM: The present study aimed to investigate the potential of standardized (Kashmir Saffron, India) Crocus sativus extract (CSE) in chronic scopolamine-induced cognitive impairment, amyloid beta (Aß) plaque, and neurofibrillary tangles (NFT) accumulation in rat brains by targeting AChE inhibition and scopolamine mechanistic effect. METHODS: The experimental animals were divided into six groups: group 1: normal control, group 2: scopolamine, group 3,4 and 5 rivastigmine tartrate, CSE (p.o. 10 mg/kg, 15 mg/kg, and 20 mg/kg) respectively. Each treatment group received scopolamine after 20 min of dosing, till 4 weeks. The effects of different treatments on learning, acquisition, and reversal memory were performed using a Morris water maze test. In addition to behavioral assessments, biochemical parameters such as AChE, IL-6, and antioxidants were measured in isolated brains. Histological observations were also conducted to assess the presence of Aß plaques and NFT. Furthermore, molecular docking was performed to explore the potential AChE inhibitory activity of the bioactive constituents of standardized CSE. RESULTS: Scopolamine produces memory impairment, and its chronic administration forms Aß plaque and NFT in rat brains. Supplementation with CSE in presence of scopolamine has shown remarkable effects on behavioural activity, special acquisition, and reversal memory. The CSE has also shown promising effects on AChE inhibition and antioxidant activity. The results of the docking study also indicate that trans-crocetin, i.e., a biologically active metabolite of Crocins, has strong AChE inhibitory activity, supported by an in vivo animal experiment. CONCLUSION: Supplementation with CSE significantly attenuates the formation of Aß plaque and NFT in the hippocampus at a dose of 20 mg/kg per day. In addition, CSE also counters scopolamine-induced neuroinflammation.

SEW2871 reduces seizures via the sphingosine 1-phosphate receptor-1 pathway in the pentylenetetrazol and phenobarbitone kindling model of drug-refractory epilepsy.

Epilepsy is a prevalent neurological disorder characterized by neuronal hypersynchronous discharge in the brain, leading to central nervous system (CNS) dysfunction. Despite the availability of anti-epileptic drugs (AEDs), resistance to AEDs is the greatest challenge in treating epilepsy. The role of sphingosine-1-phosphate-receptor 1 (S1PR1) in drug-resistant epilepsy is unexplored. This study investigated the effects of SEW2871, a potent S1PR1 agonist, on a phenobarbitone (PHB)-resistant pentylenetetrazol (PTZ)-kindled Wistar rat model. We measured the messenger ribonucleic acid (mRNA) expression of multi-drug resistance 1 (MDR1) and multi-drug resistance protein 5 (MRP5) as indicators for drug resistance. Rats received PHB + PTZ for 62 days to develop a drug-resistant epilepsy model. From day 48, SEW2871 (0.25, 0.5, 0.75 mg/kg, intraperitoneally [i.p.]) was administered for 14 days. Seizure scoring, behaviour, oxidative markers like reduced glutathione, catalase, superoxide dismutase, inflammatory markers like interleukin 1 beta tumour necrosis factor alpha, interferon gamma and mRNA expression (MDR1 and MRP5) were assessed, and histopathological assessments were conducted. SEW2871 demonstrated dose-dependent improvements in seizure scoring and neurobehavioral parameters with a reduction in oxidative and inflammation-induced neuronal damage. The S1PR1 agonist also downregulated MDR1 and MRP5 gene expression and significantly decreased the number of dark-stained pyknotic nuclei and increased cell density with neuronal rearrangement in the rat brain hippocampus. These findings suggest that SEW2871 might ameliorate epileptic symptoms by modulating drug resistance through downregulation of MDR1 and MRP5 gene expression.