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.

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.

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.

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.

Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats.

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and - 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

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.

Gonadotropic Activity of Pituitary Extract of African Catfish, Clarias gariepinus, in Mammals using Immature Wistar Rats as Models.

BACKGROUND: The pituitary glands normally produce and stores gonadotropic hormones (GnH) that are responsible for ovulation and spermiation in animals. However, whether fish pituitary extracts can elicit same effects in treated animals need elucidation as a prelude to their practical usage in animals. OBJECTIVES: The aim of this study was to investigate the oestrus-inducing potential of the pituitary gland extract of the Africa Catfish (Clarias gariepinus) in immature Wistar rats. METHODS: The experiment involved the use of 18 immature female Wistar rats and 10 male catfish brood stocks with the use of six Wistar rats per groups as follows: Group A had human chorionic gonadotropin (hCG) treatment. Group B had only normal saline treatment as the control whereas Group C had the C. gariepinus pituitary extract administration to induce oestrus with treatments occurring twice six hours apart in each group. RESULTS: There was an obvious expression of visible signs of heat and the presence of uterine horn oedema with significant (p < 0.05) increase in reproductive tract weight and uterine width and length. However, only progesterone levels increased significantly (p < 0.05) in the hCG and the C. gariepinus pituitary extract treated groups compared to other assayed hormones. CONCLUSION: These results showed that C. gariepinus pituitary extract has the capacity to induce oestrus in Wistar rats because of its gonadotropic effects, which needs further investigations at higher doses and for longer exposure periods for possible oestrus induction and synchronization in higher mammals. Further favourable results could herald the possible patent of the catfish pituitary extract for either experimental or commercial use in mammals.

Unlocking the potential of phenyl boronic acid functionalized-quercetin nanoparticles: Advancing antibacterial efficacy and diabetic wound healing.

This study investigates the novel application of Phenyl Boronic Acid Functionalized-Quercetin nanoparticles (PBA-Qt NPs) in the context of antibacterial and diabetic wound healing. The research reveals a multifaceted approach, encompassing physicochemical characterization, antioxidant activity, antibacterial potential, and wound healing efficacy. The purpose of the study was to improve wound healing and antibacterial effects of quercetin and its esterified nanoparticles with phenyl boronic acid (PBA-Qt) compared with phenytoin streptozotocin-induced diabetic rats as a model. PBA-Qt NPs were confirmed using TLC, SEM, and FTIR. They exhibited superior DPPH scavenging (84.2 ± 0.12 %) compared to PBA (59.00 ± 0.18 %) and quercetin (79.02 ± 0.17 %). PBA-Qt showed significant antimicrobial properties with ZOI against Gram-negative (30.34 ± 0.02) and Gram-positive bacteria (25.40 ± 0.03). The MIC for Pseudomonas aeruginosa was 1.41 ± 0.03 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. The MBC against Pseudomonas aeruginosa was 4.33 ± 0.02 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. PBA-Qt NPs reduced MIC for both Gram-positive and Gram-negative bacteria compared to quercetin. They enhanced wound healing by 60-99 % in infected diabetic rats, outperforming phenytoin. PBA-Qt NPs stimulated angiogenesis, tissue repair, and regeneration, improving wound closure. In diabetic and non-diabetic wounds, PBA-Qt NPs demonstrated superior wound contraction and granulation tissue formation. In conclusion, PBA-Qt nanoparticles are promising for treating diabetic chronic wounds due to reduced irritation and enhanced antibacterial and wound-healing properties.

Ultrasound-guided sciatic nerve block in Wistar rat cadavers: Relevant anatomy and injection distribution.

OBJECTIVE: To investigate the feasibility of an ultrasound-guided sciatic nerve block by describing the sonoanatomy and comparing the distribution of two volumes of bupivacaine dye solution for nerve staining. STUDY DESIGN: Randomized, experimental, assessor-blinded cadaveric study. ANIMALS: A total of 40 adult female Wistar rat cadavers. METHODS: After studying the sonoanatomy of the sciatic nerve and adjacent structures using a high-resolution linear transducer (19-5 MHz), rat cadavers were randomly divided into two groups that were administered either 0.1 mL (group 0.1) or 0.2 mL (group 0.2) of bupivacaine dye solution per nerve, delivered via an in-plane technique. The extent of nerve staining was subsequently evaluated following dissection. Statistical analysis consisted of assessing data distribution using the Shapiro-Wilk test, followed by paired t-tests for continuous data, Mann-Whitney U test and McNemar's test for categorical data. Statistical significance was defined as p < 0.05. RESULTS: The sciatic nerve was identified bilaterally as a double ellipsoid-shaped image, surrounded by a hyperechoic fascia separating the biceps femoris from the adductor muscle. The hypoechoic structure formed by the bupivacaine dye solution around the nerve was effectively visualized using ultrasound imaging. Sciatic nerve staining was successfully achieved in all pelvic limbs, with dye spread of 4.82 ± 1.55 mm and 5.47 ± 2.18 mm in groups 0.1 and 0.2, respectively (p = 0.128). CONCLUSIONS AND CLINICAL RELEVANCE: This study achieved a detailed understanding of the sonoanatomy of the sciatic nerve and its adjacent structures, highlighting the feasibility of the ultrasound-guided technique for injection in Wistar rats. Furthermore, the results show a comparable distribution of dye solution in both groups. Use of the ultrasound-guided sciatic nerve block technique in rats not only exhibits substantial potential for regional anesthesia but also opens avenues for translational studies.

3,5-Disubstituted-thiazolidine-2,4-dione hybrids as antidiabetic agents: Design, synthesis, in-vitro and In vivo evaluation.

Diabetes is one of the fastest-growing metabolic disorders, nearly doubling the number of patients each year. There are different treatment approaches available for the management of diabetes, which lacks due to their side effects. The inhibition of enzymes involved in the metabolism of complex polysaccharides to monosaccharides has proven beneficial in patients with type 2 diabetes mellitus. Two enzymes, α-amylase and α-glucosidase, have emerged as potential drug targets and are widely explored for drug development against type 2 diabetes mellitus. In this context, thiazolidine-2,4-diones (TZDs) have emerged as potential drug candidates for developing newer molecules against α-amylase and α-glucosidase. Nineteen TZD-hybrids were synthesized and evaluated in vitro α-amylase and α-glucosidase inhibitory activity. The compounds 7i, 7k, and 7p have emerged as the best dual inhibitors with IC50 of 10.33 ± 0.11-20.94 ± 0.76 µM and 10.19 ± 0.25-24.07 ± 1.56 µM against α-glucosidase and α-amylase, respectively. The derivatives had good anti-oxidant activity, displaying IC50 = 14.95 ± 0.65-23.27 ± 0.99 µM. The compounds 7k and 7p showed the best inhibition of reactive oxygen species in the PNAC-1 cells. The molecules exhibit good binding within the active site of α-amylase (PDB id: 1B2Y) and α-glucosidase (PDB id: 3W37), displaying binding energies of -7.5 to -10.7 kcal/mol and -7.4 to -10.3 kcal/mol, respectively. Further, the compounds were nontoxic (LD50 = 500-1311 mg/kg) and possessed good GI absorption. The compounds 7i, 7k, and 7p were evaluated in vivo antidiabetic activity in an STZ-induced diabetic model in Wistar rats. The compound 7p emerged as the best compound in the in vivo studies; however, the activity was lesser than that of the standard drug pioglitazone.

Multifunctional alginate/polydeoxyribonucleotide hydrogels for promoting diabetic wound healing.

A multifunctional alginate/PDRN hydrogel system by ionic crosslinking and the Schiff base reaction between oxidized alginate (OA) and PDRN was developed in the present study. Biocompatibility assessment of the PDRN-loaded OA hydrogels showed a significant enhancement in cell viability in human dermal fibroblast (HDF) cells. In addition, hydrogels showed migratory, anti-inflammatory, intracellular reactive oxygen species scavenging, and anti-apoptotic activities. In vivo studies using a streptozotocin-induced diabetic Wister rat model indicated that OA-4PDRN had the highest percentage of wound closure (96.1 ± 2.6 %) at day 14 compared to the control (79.0 ± 2.3 %) group. This was accompanied by up-regulation of vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-ß) accompanied by down-regulation of pro-inflammatory markers (IL-6, IL-1ß). Following histopathological observations, PDRN-loaded OA hydrogel ensured tissue safety and induced wound healing with granular tissue formation, collagen deposition, re-epithelialization, and regeneration of blood vessels and hair follicles. The downregulation of inflammatory cytokines (CD68) and expression of angiogenesis-related cytokines (CD31) in wound sites revealed the suppression of inflammation and increased angiogenesis, ensuring skin tissue regeneration in diabetic wound healing. In conclusion, the findings suggest that PDRN-loaded OA hydrogel has enormous therapeutic potential as a diabetic wound dressing.

Maternal diet supplemented with African walnuts enhances cortico-hippocampal gene expression and histomorphology in rat offspring.

BACKGROUND: The brain is built up during pregnancy. How it functions afterwards depends on how the expectant mother's diet nourishes it. Walnuts contain significant quantities of polyunsaturated fatty acids (PUFAs) and bioactive phytochemicals, which enhance brain health and function even with advancing age. This study examined the effects of a walnut-enriched diet (WED) on corticohippocampal histoarchitecture and gene expression in rat offspring. MATERIALS AND METHODS: Twenty-eight female adult Wistar rats (n= 7) averaging about 185 g in weight were used for this study. After mating, pregnant dams were split randomly into four groups: A (standard rat chow/control), B (WED from GD 0 - PND 21), C (WED from GD 0 - PND 1), D (WED from PND 1 - PND 21). Offspring of dams were sacrificed at adolescence (PND 35), with brain tissues of interest harvested for subsequent analyses. RESULTS: We observed no significant correlates in litter size, body, and brain weights across the experimental groups. Histomorphology revealed no distortion in cellular layering and delineation of cells in the PFC and dentate gyrus of both control and WED groups. Nissl staining intensity was enhanced in the offspring of dams exposed to WED versus the control, indicating improved proteostasis. Upregulated mRNA expression of DNMT3a, H2Ax, OPA1, and BDNF was observed in cortical and hippocampal tissues of WEDexposed offspring compared with the control group. CONCLUSION: A diet enriched with African walnuts during early development induced changes predictive of cognitive improvements and enhanced stress-response signalling, plasticity, and neural resilience in rat offspring.

Neurohistopathological Alterations Induced by Theobroma Cacao and Camellia Sinensis Extracts in Diabetic Male Wistar Rats.

Background Diabetes mellitus is often associated with neurohistopathological changes, resulting in cognitive deficits. This study aimed to explore the neurohistopathological alterations induced by Theobroma Cacao and Camellia Sinensis extracts in diabetic male Wistar rats. Methods In this randomized controlled trial, a total of 64 male Wistar rats aged between 8 and 12 weeks were allocated evenly into eight different groups. The first group, consisting of eight rats, served as the control, receiving only a standard diet with no additional treatment. The second group was treated with 150mg/kg body weight of alloxan to induce a diabetic model. The third group received a metformin treatment at a dose of 100mg/kg body weight. The fourth and fifth groups were administered with Theobroma cacao and Camellia sinensis extracts, respectively, at respective doses of 340 mg/kg and 200 mg/kg body weight. Groups six and seven were diabetic models treated with either Theobroma cacao extract (340 mg/kg) or Camellia sinensis extract (200 mg/kg). The eighth group, another diabetic model, was treated with a combination of both extracts at the same doses. Brain tissues were harvested at the end of an eight-week treatment period for histopathological evaluation. Cresyl violet staining was the method used for histopathological examination of the harvested brain tissues. Results Histopathological evaluations revealed normal neuronal structures in the control group. Alloxan-treated rats displayed significant neurodegeneration, including vacuolization and apoptosis. Metformin treatment showed moderate improvements in the neural architecture. Remarkably, Theobroma Cacao and Camellia Sinensis extracts exhibited protective effects against neurodegeneration in both non-diabetic and diabetic rats. Furthermore, a combination of both extracts in diabetic rats led to synergistic improvements in the neural structures, closely approximating normal conditions. One-way Analysis of Variance (ANOVA) revealed significant differences among the groups (F(7,56) = 24.11, p < 0.001). A Tukey post hoc test further indicated significant improvements in Metformin, Theobroma Cacao, and Camellia Sinensis-treated groups compared to the alloxan-induced diabetes model. Conclusions Both Theobroma Cacao and Camellia Sinensis extracts unveiled notable promise in countering the neurohistopathological alterations spurred by diabetes in the study. This pioneering observation accentuates the innovative possibility of utilizing these natural extracts as potential therapeutic agents for neural complications in diabetes mellitus. The compelling findings of this study contribute significantly to the existing body of research and emphatically advocate for further exhaustive exploration into the mechanistic actions of Theobroma Cacao and Camellia Sinensis extracts. The understanding gleaned from such in-depth studies could revolutionize the approach to managing and treating neural complications associated with diabetes, thereby enhancing the quality of life for affected individuals.

Drawbacks and Unexpected Advantages of the Response to Modeling Posttraumatic Stress Disorder in Old Wistar Rats.

In modeling post-traumatic stress disorder (PTSD), old Wistar rats exhibit the same general signs of a PTSD-like condition as young rats do. The ratio of testosterone to corticosterone levels was assessed as a new index and proved to provide a guideline for dividing the rat population into low- and high-anxiety groups when modeling PTSD. Several features were observed in behavior, psycho-emotional manifestations, hormone levels, and myocardial state in old rats. A sharp rise in circulating testosterone was for the first time shown to occur in old, but not young, rats in stress, contributing to a more rapid decision as to where to move in the labyrinth space. Priority data were obtained on dysfunctional accumulation of mitochondria in the myocardium in intact and stressed old rats. The information obtained may be useful in developing drugs against harmful consequences of PTSD and senile changes in the myocardium.

Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.

Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method. In 3 months after hypertension modeling, glomerular filtration rate decreased by 2 times in comparison with the control (31.2±0.44 and 62.3±1.31 µl/min/100 g, respectively; p<0.001). Our findings can indicate the formation of hypertensive nephroangiosclerosis in rats with experimental arterial hypertension. It was found that kidney damage in hypertensive rats is associated with hypofiltration.

The protective role of L-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats.

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. L-Carnitine (LC) is regarded as the "gatekeeper" in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.

[Melatonin reverses oxidative damage in the submandibular gland of rats treated with Cyclophosphamide]. / Melatonina revierte el daño oxidativo en glándula submandibular de ratas tratadas con Ciclofosfamida.

Objetive: Cyclophosphamide (Cf) produces oxidative damage in rat submandibular gland (GSM). In the present work we evaluated the antioxidant protective effect of melatonin (MLT) in GSM of rats treated with Cf. Methods: 40 adult male Wistar rats were divided into 5 groups (G): G1: control; G2: Control+Ethanol: treated with 1% ethanol for 10 consecutive days. On days 11 and 12 they received a dose of saline; G3: Cf: treated with 1% ethanol for 12 days, days 11 and 12 they received an intraperitoneal (i.p.) dose of Cf 50 mg/Kg/kg of saline. ) of Cf 50 mg/kg bw; G4: Cf + MLT: MLT (5 mg/kg bw, intraperitoneal, dissolved in 1% ethanol) was administered daily, days 11 and 12 received Cf same as G3; G5: MLT: treated 12 consecutive days with MLT (same dose as G4). After 12 hours of fasting, animals were anesthetized to obtain both submandibular glands, then they were sacrificed. Uric acid (UA), lipid peroxides (LPs), aqueous peroxides (APs) and superoxide dismutase (SOD) activity were measured in submandibular gland homogenate. Statistical analysis: we used ANOVA and Bonferroni test pos hoc, considering significant p<0.05. Results: Cf treatment decreased AU concentration and SOD activity (AU, mg/mg prot., G1: 2.50±0.68; G2: 2.18±0.13; G3: 0.54±0.09* G4: 1.95±0.24#, G5: 2.64±0.47, *p<0.01 G3 vs G1, G2, G4; #p<0.01 G4 vs G3 and G5; SOD, U/mg prot, G1: 4.57±0.95, G2: 4.79±0.94, G3: 2.18±0.53*, G4: 5.13±1.10, G5: 5.09±0.39, *p< 0.01 G3 vs G1, G2, G4 and G5). MLT treatment prevented these effects. In addition, Cf increased PL and PA formation. Conclusion: MLT improved the redox status in GSM of Cf-treated rats. MLT could prevent oxidative processes in GSM produced by Cf.

Objetivo: Ciclofosfamida (Cf) produce daño oxidativo en glándula submandibular (GSM) de ratas. En el presente trabajo se evaluó el efecto protector antioxidante de melatonina (MLT) en GSM de ratas tratadas con Cf. Método: Se utilizaron 40 ratas Wistar machos adultas divididas en 5 grupos (G): G1: control; G2: Control+Etanol: tratados con etanol al 1% durante 10 días consecutivos. Los días 11 y 12 recibieron una dosis de solución salina; G3: Cf: tratados con etanol al 1% durante 12 días, días 11 y 12 recibieron una dosis intraperitoneal (i.p.) de Cf de 50 mg/Kg de pc; G4: Cf + MLT: se administró diariamente MLT (5 mg/Kg pc, intraperitoneal, disuelta en etanol al 1%), días 11 y 12 recibieron Cf igual que G3; G5: MLT: tratamiento 12 días consecutivos con MLT (igual dosis de G4). Los animales fueron anestesiados, extirpándose ambas GSM y sacrificados, previo ayuno 12 hs. Se midió la concentración de ácido úrico (AU), peróxidos lipídicos (PL) y acuosos (PA) y actividad de superóxido dismutasa (SOD) en homogenato de GSM. Análisis estadístico: ANOVA y test de bonferroni, considerando significativo p<0,05. Resultados: El tratamiento con Cf disminuyó la concentración de AU y la actividad de SOD (AU, mg/mg prot., G1: 2,50±0,68; G2: 2,18±0,13; G3: 0,54±0,09* G4: 1,95±0,24#, G5: 2,64±0,47, *p< 0,01 G3 vs G1, G2, G4; #p< 0,01 G4 vs G3 y G5; SOD, U/mg prot., G1: 4,57±0.95, G2: 4,79±0,94, G3: 2,18±0,53*, G4: 5,13±1,10, G5: 5,09±0,39, *p< 0,01 G3 vs G1, G2, G4 y G5). El tratamiento con MLT previno esos efectos. Además, Cf aumentó la formación PL y PA. Conclusión: MLT mejoró el estado redox en GSM de ratas tratadas con Cf. MLT podría prevenir los procesos oxidativos en GSM producidos por Cf.

Validation and development of RP-HPLC method for quantification of glibenclamide in rat plasma and its application to pharmacokinetic studies in wistar rats.

Herein, we report a novel, simple, specific, accurate and cost-friendly validated reverse phase-high performance liquid chromatographic (RP-HPLC) method for the quantification of second generation sulphonylurea based antidiabetic drug, glibenclamide (GLB) in rat plasma and its application to calculate pharmacokinetic parameters in wistar rats. The internal standard used was flufenamic acid. The chromatographic separation was conducted on C18 column (250 mm × 4.6 mm x 5 µm, Agilent-Zorbax, SB) using isocratic elution with mobile phase containing Acetonitrile: Water (1:1; v/v) pH adjusted to 4.0 with 0.03 % glacial acetic acid and detected by photo-diode array as detector. Calibration curves made in the rat plasma were linear in the range of 50-1200 ng/ml with r2 = 0.998. The LLOQ was 40 ng/ml. This method was effectively applied for pharmacokinetic studies of Glibenclamide following administration through oral route as solid dispersion formulation to Wistar rats. Several methods are available in the literature which can be employed for the quantification of Glibenclamide but such methods are tedious, provide lower sensitivity, less simultaneous resolution and are time-consuming. Therefore the present methods suits best for the quantification of Glibenclamide from Wistar rats.

Inhibition of sepsis-induced pancreatic injury by leukotriene receptor antagonism via modulation of oxidative injury, and downregulation of inflammatory markers in experimental rats.

The purpose of this study is to investigate the effect of montelukast on lipopolysaccharide (LPS)-induced pancreatitis. Adult male Wistar rats were divided into 5 groups: normal control, control montelukast, LPS group, and two LPS + montelukast-treated groups. Acute pancreatitis (AP) was induced by a single dose of LPS (6 mg/kg, i.p.), while montelukast was given in two different doses (10 and 20 mg/kg/day) for 3 consecutive days prior to the injection of LPS. AP was demonstrated by significant increases in serum levels of lactate dehydrogenase (LDH) and pancreatic enzymes lipase and amylase. Proinflammatory response activation was evident by elevated serum levels of nitric oxide (NO) and increased pancreatic concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1). The activity of myeloperoxidase (MPO), a neutrophil infiltration marker, has also been increased. Oxidative stress was confirmed by significant increases in the concentrations of lipid peroxides measured as thiobarbituric acid reactive substances (TBARS) and decreases in the concentrations of reduced glutathione (GSH) in the pancreatic tissues of animals treated with LPS. Histological examination confirmed the biochemical alterations. Montelukast treatment reversed all these biochemical indices and histopathological changes that LPS induced. Montelukast reduced the increase in serum levels of lipase, amylase, LDH, total nitrite/nitrate, TNF-α, IL-1ß, and ICAM-1. MPO activities and TBARS concentrations were also suppressed while GSH content was increased in pancreatic tissues. These results show that montelukast may be a beneficial pharmacological agent in protection against LPS-induced oxidative pancreatic injury by inhibiting neutrophil infiltration, counteracting oxidative stress, and suppressing inflammatory mediators.