Healthy Rats Research Articles

Antilithiatic Activity of Arbutus Pavarii (Shemeri) Extract on Ethylene Glycol Induced Lithiasis in Rats

Objectives. The objective of this study was to investigate the antilithiatic activity of shemeri (Arbutus Pavarii) on ethylene glycol-induced urolithiasis in male albino rats. Methods. 24 healthy male albino rats were divided into 4 groups. The rats in group A served as the normal control group. Group B (EG-treated group) rats received 0.75% ethylene glycol for three weeks followed by drinking water for the next 3 weeks. Group C (preventive group) rats received 0.75% ethylene glycol along with shemeri for six weeks. Group D (treatment group) rats received 0.75% ethylene glycol for three weeks then supplemented with shemeri aqueous solution. After six weeks, various levels of oxalate, calcium, and phosphate in urine and serum levels of creatinine, urea, uric acid, phosphate, calcium, and sodium were measured. Histopathological examination for kidney samples was also conducted. Results. In comparison to the EG-treated group, oral administration of Arbutus Pavarii (shemeri) significantly lowered elevated levels of creatinine, urea, and uric acid while, significantly increased levels of phosphate, calcium, and sodium in the serum. Shemeri also reduced elevated levels of urinary oxalate, calcium, and phosphate. Histopathological examination showed noticeable kidney lesions in group (B), but these lesions improved in groups (C, and D). Conclusion. This study suggests that shemeri is a promising and effective plant in prevention and treatment of Ethylene glycol-induced urolithiasis in male albino rats.

Determination of SOD Activity of Vayasthapana Drugs Guduchi Kwatha, Punarnava Kwatha and Punarnava in Conjunction with Guduchi Kwatha in healthy Wistar Rats

SOD (Superoxide dismutase) belongs to a class of enzymes and stands as the primary defense against reactive oxygen species (ROS). Guduchi (Tinospora cordifolia) and punarnava (Boerhavia diffusa) are believed to have rasayana (rejuvenating) and vayasthapana (anti-aging) properties in ayurveda. Several studies show the antioxidant properties of individual drugs in disease-induced conditions but a gap was observed in the study of the antioxidant properties of guduchi and punarnava in normal healthy subjects and the combined effect of punarnava in conjunction with guduchi. To gain insight into the potential effects of these herbal formulations on SOD activity study was planned. The Animal experiment was carried out as per the guidelines of CPCSEA (Committee for Control and Supervision of Animal Experiment) laboratory animals after seeking permission from IAEC, with 32 (24+8 considering 20% dropout) healthy male Wistar rats. Rats are divided into four groups, 8 (6+2) animals in each. Distilled water, guduchi kwath (GK), punarnava kwath (PK), and a combination of guduchi and punarnava kwath (GPK) given orally with help of 2 ml syringe in doses 8.1 ml/kg in different 4 groups respectively as Normal control (NC) group, Trial group of guduchi (TGG), Trial group of punarnava (TGP), Trial group of guduchi and punarnava (TGGP) for 30 days. The blood sample through orbital punctures of all 24 animals was collected for assessment SOD levels before administration of the test drug and after 30 days of intervention. (Cu-Zn) SOD activity was determined by using a simple and rapid method with a spectrophotometer in the laboratory. The TGG (P value 0.001), TGP (P value 0.035), and TGGP (P value 0.010) groups did exhibit statistically significant changes in SOD levels after giving GK, PK, and GPK intervention while the NC (P value 0.335) group did not show a significant difference. Higher SOD activity indicates a more antioxidant defense mechanism, thus GK, PK and GPK can protect against oxidative damage which supports the potential slowing down age-related changes and promoting healthier aging.

Strontium-containing mineralized phospholipid coatings improve osseointegration in osteoporotic rats.

Surface treatments play an important role in enhancing the osseointegration of Titanium (Ti) and its alloys. This study introduces a method employing biomimetic hydroxyapatite (Hap) deposition guided by molecularly organized phospholipids, affixed to the metal implant surface. Using the Langmuir-Blodgett technique, phospholipids were deposited onto Ti-screws by using CaCl2 or CaCl2/SrCl2 aqueous solution in the subphase of a Langmuir trough in the target proportion (i.e. 10 and 90 mol% of Sr2+ in relation of Ca2+) followed by immersion in phosphate buffer and in supersaturated simulated body fluid. Coating composition and morphology were evaluated using infrared spectroscopy and scanning electron microscopy, respectively, while contact angle measurements assessed coating wettability and surface energy. Randomized screws were then implanted into the tibias of healthy and osteoporotic female rats (G1: Control-Machined, G2: Hap, G3: HapSr10, G4: HapSr90). Osseointegration, assessed 60 days post-implantation, included reverse torque, fluorochrome area, bone tissue-screw contact area, and linear extent of bone-screw contact. Results, grouped by surface treatment (Machined, Hap, HapSr10, HapSr90), revealed that the deposition of Hap, HapSr10, and HapSr90 resulted in thin and rough coatings composed of hydroxyapatite (Hap) on the screw surface with nanoscale pores. The coatings resulted in increased wettability and surface energy of Ti surfaces. The minerals are chemically similar to natural bone apatite as revealed by FTIR analysis. In vivo analyses indicated higher torque values for strontium-containing surfaces in the osteoporotic group (p = 0.02) and, in the control group superior torque for screw removal on the Hap surface (p = 0.023). Hydroxyapatite-treated surfaces enhance morphology, composition, and reactivity, promoting screw osseointegration in healthy and osteoporotic female rats. The incorporation of strontium into the mineral phase has been proposed to not only stimulate osteoblast activity but also reduce osteoclastic resorption, which may explain the improved outcomes observed here in experimental osteoporotic conditions.

Aerobic exercise improves spatial memory in a rat model of meningitis

Infections of the nervous system, such as acute bacterial meningitis, pose serious health problems that require immediate intervention. In experimental animals, exposure to lipopolysaccharide (LPS) is used to induce meningitis. Aside from drug intervention to reduce inflammation in meningitis, aerobic exercise helps to maintain the regulatory mechanisms of brain homeostasis through anti-inflammatory mechanisms. The aim of this study was to evaluate the effect of aerobic exercise on malondialdehyde (MDA), nuclear factor-kappa B (NF-κB), insulin-like growth factor 1 (IGF-1), endothelial nitric oxide synthase (eNOS), brain-derived neurotrophic factor (BDNF), apoptosis, and spatial memory. A four-week experimental study was conducted using 18 rats, which were randomly divided into three different groups (six rats per group): healthy rats as negative controls (non-meningitis), a treatment group treated with antibiotic treatment (meningitis group), and a third group (aerobic exercise group) treated with antibiotics and aerobic exercise following LPS-induced meningitis. Data were analyzed using a one-way analysis of variance (ANOVA) test, and the comparison between groups used the Bonferroni post-hoc test. The results showed that aerobic exercise significantly reduced MDA (p<0.001), NF-κB (p=0.035), and apoptosis (p=0.020) while increasing the serum levels of IGF-1 (p<0.001), eNOS (p=0.011), and BDNF (p=0.001) levels. Improvement in spatial memory was significant in the aerobic exercise group (p<0.001). This study suggested that aerobic exercise could be a promising adjunct therapy in meningitis management strategies, particularly due to its effect on improving spatial memory. Further clinical trials are needed to confirm these findings for clinical use.

Cerebral and myocardial kinetics of [11C]acetoacetate and [11C]β-hydroxybutyrate: A comparative crossover study in healthy rats

BackgroundKetone metabolism has been studied using positron emission tomography (PET) with the radiotracers [11C]acetoacetate and [11C]β-hydroxybutyrate. However, whether these two radiotracers actually yield equivalent estimates of cerebral and myocardial ketone metabolism has not yet been investigated. This study aimed to investigate and compare the kinetics of both tracers in the brain and heart of healthy rats under varying levels of circulating ketones at baseline and after a single-dose exogenous ketone ester (KE) supplement. MethodsSix healthy Sprague-Dawley rats each underwent two scans with each tracer: one following oral KE administration and one with a placebo. Cerebral kinetic parameters (Ki, VT, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (K1, k2, and VT) were derived using a 1-tissue compartment model. Parameters were compared through mixed-effects, correlation, and Bland-Altman analyses. ResultsGlobal CMR increased 3–4-fold in the KE group versus placebo, with strong positive correlations between CMR and plasma ketone levels for both tracers. Correlations between [11C]acetoacetate and [11C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as Ki (ρ = 0.40) and for VT (ρ = 0.38) but strongly positive for absolute uptake, CMR (r = 0.84), with a non-significant mean bias of −0.03. In contrast, myocardial kinetics showed only non-significant weak to moderate correlations between the radiotracers (K1 (r = 0.04), k2 (r = −0.27), and VT (ρ = 0.43)), with no systematic biases. Conclusion[11C]acetoacetate and [11C]β-hydroxybutyrate can be used interchangeably for measuring global CMR in healthy rats but differ in certain cerebral and myocardial kinetics. Whether these findings are generalizable to pathological conditions warrants further studies to explore the kinetics of these tracers in disease models.

Adipokines level in plasma, hypothalamus, ovaries, and adipose tissue of rat's polycystic ovary syndrome model

Research questionDo the levels of adipokines (adiponectin, apelin, chemerin and vaspin) in plasma, hypothalamus, ovaries, and periovarian adipose tissue differ during polycystic ovarian syndrome (PCOS)? DesignThe PCOS was induced in rats by oral administration of nonsteroidal aromatase inhibitor letrozole. To determine the plasma levels of adiponectin, apelin, chemerin, and vaspin we performed enzyme-linked immunosorbent assays. To assess the expression (gene and protein) and immunolocalization of these adipokines and their receptors, namely Adipor1 and Adipor2 for adiponectin; Aplnr for apelin; Ccrl2, Cmklr1, and Gpr1 for chemerin; and Grp78 for vaspin in the hypothalamus, ovaries, and periovarian adipose tissue we conducted by real-time PCR, Western blot and immunohistochemistry, respectively. ResultsWe noted that PCOS modulates the plasma levels of adipokines (decreased adiponectin, increased apelin, chemerin, and vaspin) and the expression of adipokines and their receptors in the hypothalamus, ovaries, and periovarian adipose tissue compared with healthy rats. ConclusionsThis study confirmed a strong relationship between PCOS and adipokines and suggest that adipokines may be a biomarker of PCOS.

122 - Functional role of the urothelium in nitrergic signaling in the isolated healthy and inflamed rat urinary bladder

122 - Functional role of the urothelium in nitrergic signaling in the isolated healthy and inflamed rat urinary bladder

Stiffness-induced modulation of ERG transcription factor in chronic liver disease

Chronic liver disease (CLD) is characterised by liver sinusoidal endothelial cells (LSECs) dysfunction. Mechanical forces and inflammation are among the leading factors. ETS-related gene (ERG) is an endothelial-specific transcription factor, involved in maintaining cell quiescence and homeostasis. Our study aimed to understand the expression and modulation of ERG in CLD. ERG expression was characterised and correlated to clinical data in human liver cirrhosis at different disease stages. ERG dynamics in response to stiffness and inflammation were investigated in primary healthy and cirrhotic rat LSEC and in human umbilical vein endothelial cells (HUVECs). ERG is markedly downregulated in cirrhosis independently of disease stage or aetiology and its expression is modulated by substrate stiffness in ECs. Inflammation downregulates ERG in cells on physiological stiffness, but not on high stiffness, suggesting a complementary role of inflammation and stiffness in suppressing ERG. This study outlines ERG as an LSEC inflammation and stiffness-responsive transcription factor in cirrhosis.

New Therapeutic Rargets for Cynodon Dactylon in Atherosclerosis: Attenuation of TMAO Generation and Down-regulation of TLR-4 in Rats

Purpose: Atherosclerosis (AS) is a chronic disease with worldwide incidence. The current study was conducted to highlight the molecular pathogenesis of AS and equal effectiveness of cynodon dactylon’s ethanolic extract (CDE) on the AS-induced injuries. Methods: Atherosclerosis was induced experimentally in healthy male rats with a hypercholesterolemic diet (HCD) for 24 weeks. The HCD-received animals were either treated with normal saline or various doses of CDE and/or atorvastatin. After 24 weeks of the treatment period, the effects of HCD on lipid profile, oxidative/nitrosative stress status, inflammatory enzymes (LDH, ALP and CKMB) activities, trimethylamine oxide (TMAO) concentration in serum along with the expression of TLR-4 (qPCR) and CD31 (Immunohistochemistry) in coronary and aorta were analyzed Results: CDE was able to reduce the HCD-enhanced cholesterol and triglycerides. The HCDelevated activities of LDH, ALP and CK-MB were declined by CDE. The antioxidant potency of CDE was comparable with atorvastatin on HCD-induced oxidative/nitrosative stress. The serum concentration of TMAO was lowered (1.7-fold) by CDE in a dose-dependent manner, while CD31 expression in the endothelial of coronary arterials and aorta in CDE and atorvastatin-received animals was remarkably increased. The up-regulated expression of TLR-4 (2.5-fold) at mRNA level was regulated significantly (p < 0.05) and returned to normal level by CDE treatment. Conclusion: Results of the current study indicate that the up-regulation of TLR-4 as a main inflammatory gene and elevation of TMAO are involved in the pathophysiology of AS. Moreover, the protective effects of CDE on AS may be attributed to its anti-inflammatory and hypolipidemic properties.

Anti-tumor property of Argemone mexicana leaves methanol extracts against 7, 12- Dimethylbenz[a]anthracene (DMBA) induced mammary tumors in experimental rats

Background: Breast cancer is a complex and multistage process. Many natural compounds are available for an effective and efficient alternative method against breast cancer. This study focused on the anti-cancer activity of Argemone mexicana leaf extract on Dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in experimental rats. Materials and Methods: Argemone mexicana Leaves (AML) were collected, extracted by soxhlet apparatus with methanol solvent, and analyzed by Gas Chromatography and Mass-Spectroscopy (GCMS). Healthy Female Sprague-Dawley rats (7-8 weeks and 100 ± 20 g) were divided in five groups and used to induce mammary tumors by DMBA [25 mg/kg/ Subcutaneous (s.c.)]. After developing a palpable nodule (10-12 weeks after DMBA), the rats were treated with AML extract [200 and 400 mg/kg/Body Weight (b.w.)] and Tamoxifen (TAM 10 mg/kg) orally for 12 weeks. Body weight, tumor weight and volume measurements, lipid peroxidation, antioxidant and tumor marker [Carcinoembryonic Antigen (CEA)] levels, and histological investigations were assessed. Results: Following AML treatment, there was a reduction in weight and volume (P< 0.01) of breast tumor, as well as a significant decrease in levels of lipid peroxidation and tumor marker CEA (P < 0.001) and improved Superoxide Dismutase (SOD), Reduced glutathione (GSH), and caspase levels (P < 0.001). In cytological results, AML improved the cellular architecture, and significant restoration in histopathological examinations revealed a tumor with minimal glandular epithelium proliferation, a decrease in mitotic figures, and nuclear alterations. Conclusion: The study suggests that AML extract has a chemoprotective effect against DMBA-induced mammary tumors in experimental animals, specifying its possibility as a therapeutic agent for breast cancer treatment.

ALLEVIATION OF ARSENIC INDUCED THYROID DYSFUNCTION AND BODY WEIGHT ALTERATIONS BY CURCUMIN

Background: Arsenic is notorious for being used in many homicidal cases. This study was designed to observe the toxic effects of low dose of arsenic on thyroid gland and body weight and its amelioration by curcumin. Method: Thirty healthy female Sprague Dawley rats (body weight ~230 g) were procured from The National Institute of Health Islamabad. After one week of acclimatization, animals were randomly divided into three groups (n=10 each), e.g., Control group (C), Experimental group-1 (E1) and Experimental group-2 (E2). The duration of the experiment was one month. Weight of the animals was checked before and at the end of experiment. All the animals were continued on standard diet and distilled water during experimental period. E1 was given 10 µg/10 mL of arsenic by oral gavage daily. E2 was given 10 µg/10 mL of arsenic along with Curcumin (50 mg/Kg body weight/day). At the end of experiment, the rats were euthanized to draw the blood and removal of thyroid gland. Serum Triiodothyronine, Tetraiodothyronine and Thyroid Stimulating Hormone were measured by ELISA. Histological changes were observed after haematoxylin and eosin staining. Statistical analysis was done on SPSS-22 and p?0.05 was considered significant. Results: The histological findings of thyroid gland, body weight and serum T3, T4 and TSH in E1 exhibited abnormal results. E2 group showed the protecting role of curcumin suggesting protective role of curcumin. Conclusion: Curcumin has protective effects against arsenic induced thyroid disruption and body weight alterations. Pak J Physiol 2024;20(3): DOI: https://doi.org/10.69656/pjp.v20i3.1686

Correlation between Kupffer Cell Infiltration and Liver Parenchymal Cell Damages in Immunosuppressed Drugs-Induced Rats

The liver is the largest organ in the body, composed of both parenchymal and non-parenchymal cells. Chemical substances and various drugs can induce liver injury and involve Kupffer cells which are non-parenchymal cells that release biologically active substances, promoting pathological processes. This study aimed to evaluate the correlation between the number of Kupffer cells and liver parenchymal cell damages in immunosuppressed, drug-induced rats. The study was conducted from July to December 2019 at the Oral Biology Laboratory of the Faculty of Dentistry and the Biochemical Laboratory of the Faculty of Medicine at Universitas Hang Tuah Surabaya. Twelve healthy male Wistar rats were divided into two groups: Healthy (H) and Immunosuppressed Drug-Induced (ID) groups. Immunosuppression was induced using dexamethasone (0.5 mg/day/rat), administered orally for 14 days, combined with tetracycline (1%/day/rat). Liver samples from all rats were examined for Kupffer cell count and parenchymal cell damages were assessed using a light microscope with 400x magnification. Results revealed a significant difference in the number of Kupffer cells and liver parenchymal cell damages between the H and ID groups (p<0.05). Pearson correlation analysis indicated a significant correlation between Kupffer cell number and parenchymal cell damages (p=0.000). Continuous administration of immunosuppressive drugs may activate Kupffer cells, leading to damage of liver parenchymal cells. In conclusion, the infiltration of Kupffer cells is associated with liver parenchymal cell damages, mediated by various factors in the immunosuppressed drug-induced rat model.

Antidiabetic and Antihyperlipidemic Activity of Ethanolic Extract of Mentha viridis in Alloxan Induced Diabetic Rats

This research was designed to examine the phytochemicals of Mentha viridis (M. viridis) ethanolic extract and the antidiabetic and antihyperlipidemic activities in alloxan-induced animal models. Diabetes was induced chemically by administering a unit dose of alloxan at 120 mg/kg BW. After alloxan induction, hyperglycemic rats were dealt with ethanolic extract of leaf and whole plant, metformin, and a mixture of leaf extract with metformin and whole plant extract with metformin for two weeks. Ethanolic extract of leaf and whole plant, metformin, and a combination of both leaf and whole plant extract with metformin therapies reduced glucose levels in the blood compared with the diabetic negative control group after two weeks of treatment. However, among the therapies, the ethanolic leaf extract and the combination of whole plant extracts with metformin were found to be the most effective (p<0.05), with reductions of 62.82% and 72.89%, respectively. After diabetes induction, the serum level of TG (triglycerides), TC (total cholesterol), LDL-C (low-density lipoprotein-cholesterol) escalated notably (p<0.05), and HDL-C (high-density lipoprotein-cholesterol) level decreased remarkably (p<0.05) in hyperglycemic rats as opposed to healthy normal rats. Ethanolic leaf extract and a combination of whole plant extract with metformin significantly minimized the elevated extent of TG and LDL-C. They surged HDL-C, but the TC level was reduced by whole plant extract only after two weeks of treatment. The standard procedures were used to identify the phytochemical compounds of the medicinal plant M. viridis. The phytochemical compounds such as alkaloids, resins, tannins, phenols, flavonoids, steroids, and terpenoids appeared in the ethanolic leaf extract of M. viridis. The findings suggest that M. viridis might provide better glycemic control and hypolipidemic effect in diabetic rats when administered alone or combined with oral antidiabetic agents. Incorporating M. viridis extract with metformin in improving hyperglycemic and hyperlipidemic conditions in diabetic rats proves that M. viridis has a synergistic effect, which could enhance the antidiabetic activity of oral hypoglycemic agents.

Curcumin-mediated enhancement of lung barrier function in rats with high-altitude-associated acute lung injury via inhibition of inflammatory response

BackgroundExposure to a hypobaric hypoxic environment at high altitudes can lead to lung injury. In this study, we aimed to determine whether curcumin (Cur) could improve lung barrier function and protect against high-altitude-associated acute lung injury.MethodsTwo hundred healthy rats were randomly divided into standard control, high-altitude control (HC), salidroside (40 mg/kg, positive control), and Cur (200 mg/kg) groups. Each group was further divided into five subgroups. Basic vital signs, lung injury histopathology, routine blood parameters, plasma lactate level, and arterial blood gas indicators were evaluated. Protein and inflammatory factor (tumor necrosis factor α (TNF-α), interleukin [IL]-1β, IL-6, and IL-10) concentrations in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method and enzyme-linked immunosorbent assay, respectively. Inflammation-related and lung barrier function-related proteins were analyzed using immunoblotting.ResultsCur improved blood routine indicators such as hemoglobin and hematocrit and reduced the BALF protein content and TNF-α, IL-1β, and IL-6 levels compared with those in the HC group. It increased IL-10 levels and reduced pulmonary capillary congestion, alveolar hemorrhage, and the degree of pulmonary interstitial edema. It increased oxygen partial pressure, oxygen saturation, carbonic acid hydrogen radical, and base excess levels, and the expression of zonula occludens 1, occludin, claudin-4, and reduced carbon dioxide partial pressure, plasma lactic acid, and the expression of phospho-nuclear factor kappa.ConclusionsExposure to a high-altitude environment for 48 h resulted in severe lung injury in rats. Cur improved lung barrier function and alleviated acute lung injury in rats at high altitudes.

Exploring Liraglutide in Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy Model in Rats: Impact on Inflammation, Mitochondrial Function, and Behavior.

Background/Objectives: Glucagon-like peptide-1 receptor agonists such as liraglutide are known for their neuroprotective effects in neurodegenerative disorders, but their role in temporal lobe epilepsy (TLE) remains unclear. We aimed to investigate the effects of liraglutide on several biological processes, including inflammation, antioxidant defense mechanisms, mitochondrial dynamics, and function, as well as cognitive and behavioral changes in the TLE model. Methods: Low-dose, repeated intraperitoneal injections of lithium chloride-pilocarpine hydrochloride were used to induce status epilepticus (SE) in order to develop TLE in rats. Fifty-six male Sprague Dawley rats were subjected and allocated to the groups. The effects of liraglutide on inflammatory markers (NLRP3, Caspase-1, and IL-1β), antioxidant pathways (Nrf-2 and p-Nrf-2), and mitochondrial dynamics proteins (Pink1, Mfn2, and Drp1) were evaluated in hippocampal tissues via a Western blot. Mitochondrial function in peripheral blood mononuclear cells (PBMCs) was examined using flow cytometry. Cognitive-behavioral outcomes were assessed using the open-field, elevated plus maze, and Morris water maze tests. Results: Our results showed that liraglutide modulates NLRP3-mediated inflammation, reduces oxidative stress, and triggers antioxidative pathways through Nrf2 in SE-induced rats. Moreover, liraglutide treatment restored Pink1, Mfn2, and Drp1 levels in SE-induced rats. Liraglutide treatment also altered the mitochondrial function of PBMCs in both healthy and epileptic rats. This suggests that treatment can modulate mitochondrial dynamics and functions in the brain and periphery. Furthermore, in the behavioral aspect, liraglutide reversed the movement-enhancing effect of epilepsy. Conclusions: This research underscores the potential of GLP-1RAs as a possibly promising therapeutic strategy for TLE.

Evaluation of the Antihyperlipidemic Effect of Encapsulated Octacosanol for Lipid-Lowering Effect Against High-Fat Diet-Induced Hyperlipidaemia in Experimental Rats.

Background: Elevated blood lipid levels, or hyperlipidemia, are the main risk factors for cardiovascular illnesses and are frequently brought on by high-fat diets. Objectives: In this work, high-fat diet-induced hyperlipidemia in experimental rats is used to examine the antihyperlipidemic efficacy of a test formulation containing 1-octacosanol. Method: A healthy female Wistar rat was utilized for investigation, separated into four groups: normal, disease, standard control, and test group, receiving the 1-octacosanol formulation. Results: Hyperlipidemia was induced in the rats through a high-fat diet over 28 days, followed by a 28-day treatment period. Various parameters, including lipid profile (LDL, TC, TG, VLDL, HDL), body weight and antioxidant properties (MDA, SOD, GSH), were evaluated. The results showed that the 1-octacosanol formulation significantly reduced body weight and improved lipid profiles by decreasing levels of TC, TG, LDL and VLDL while increasing HDL levels. Additionally, the formulation exhibited notable antioxidant properties, contributing to its lipid-lowering effects. Statistical analysis using ANOVA and multiple comparison tests confirmed the significance of these findings, underscoring the therapeutic potential of 1-octacosanol in managing hyperlipidemia and mitigating associated cardiovascular risks. Conclusion: The test formulation of 1-octacosanol demonstrated a significant antihyperlipidemic effect in rats with high-fat diet-induced hyperlipidemia. The treatment effectively reduced serum levels of total cholesterol, triglycerides, LDL and VLDL while increasing HDL cholesterol levels. These marks suggest that 1-octacosanol has the potential as a therapeutic agent for managing hyperlipidemia, a key risk factor for cardiovascular diseases.

Combination Therapy with Vitamin D and Metformin: A Potential Approach to Mitigate Testicular Dysfunction in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a multifactorial disease that cannot be linked to a single pathway, causing the observed heterogeneity among T2DM patients. Despite this level of heterogeneity, T2DM is majorly managed by metformin (MET) monotherapy. However, recent findings have associated long-term metformin intake with progressive oxidative pancreatic β cell damage as the disease progresses. Hence, a significant number of patients treated with MET need an alternate therapy. Hence, identifying drug combinations that can effectively alleviate different diabetes complications would serve as a more promising therapy that can translate into active use. Hence, this study was designed to explore the possible synergistic effect of vitamin D and metformin on T2DM-induced testicular dysfunction. Thirty healthy male Wistar rats (weight: 120-150 g and age: 10 ± 2 weeks) were randomly divided into control, diabetes untreated (HFD+STZ), diabetes + vitamin D (1000 IU/kg), diabetes + metformin (180 mg/kg), and diabetes + vitamin D + metformin. All treatments lasted for 28 days and animals were sacrificed using IP injection of ketamine and xylaxine (40 and 4 mg/kg respectively). Vitamin D improved the ameliorative effect of metformin on T2DM-induced hyperglycemia and lipid dysmetabolism, accompanied by a significant decrease in testicular lactate dehydrogenase and lactate. Also, vitamin D + metformin significantly increased serum luteinizing hormone, follicle-stimulating hormone, testosterone, and testicular 5α reductase activities. Furthermore, vitamin D improved the anti-inflammatory and antioxidant effects of metformin by significantly decreasing T2DM-induced increase in testicular interleukin 1beta, interleukin 6, TNF-α, nitric oxide, and NF-κB and increasing T2DM-induced decrease in interleukin 10, glutathione, superoxide dismutase, catalase, GPx, and Nrf2. Vitamin D enhanced the ameliorative effect of metformin on T2DM-induced testicular dysfunction.

Anti-arthritic studies of ethnomedicine Gaultheria trichophylla Royle extract and salicylate-rich fraction using complete Freud's adjuvant-induced rats: molecular docking and network pharmacology analysis.

Gaultheria trichophylla Royle is a traditional treatment for inflammatory conditions including arthritis. The objective was to evaluate the anti-arthritic activity of the extracts and salicylate-rich fractions through adjuvant-induced arthritis, histopathological analysis, radiological imaging, hematological, biochemical parameters along with using bioinformatic tools. In vivo anti-arthritic efficacy of the extract and SRF (at 100, 200, 300, and 150mg/kg doses) was assessed using healthy albino rats. Molecular docking of identified compounds along with network pharmacology analysis helped to determine the route of action of drug. Both the extract and SRF showed dose-dependent anti-arthritic activity by decreasing the joint diameter, increase in pain threshold and body weight compared with negative control group. Along with SRF (150mg/kg), EEGT (300 and 200mg/kg) shows significant (P < 0.01) anti-arthritic activity by lowering levels of WBC, platelets, serum C-reactive protein (CRP), and rheumatoid factor (RF) and raising levels of RBC and Hb. The modified biochemical measures (AST, ALT, ALP, and total protein level) further supported the anti-arthritic action. Histopathology and radiology study showed that EEGT (300 and 200mg/kg), SRF (150mg/kg) and diclofenac (10mg/kg) inhibited joint destruction. GCMS analysis showed the presence of methyl salicylate, sitosterol, calcifediol, and ergosta-5,22-dien-3-ol, acetate as important bioactive constituents. Moreover, as the significant node in the pharmacology network and docking against TNF-α, a classical therapeutic target in RA showed potential of G. trichophylla in treatment of RA. The results showed that G. trichophylla have effectively reduced the inflammation of the joints.

Development of a Short-Term Embolic Agent Based on Cilastatin for Articular Microvessels.

Background and Objectives: This study aimed to develop an embolic agent with short-term embolic effects using cilastatin as the basic material. Materials and Methods: The particle size distribution of 25 mg cilastatin-based short-term embolic agents was evaluated microscopically under three different mixing conditions. A total of thirty-six healthy male Sprague Dawley rats were divided into four groups. Each group of six rats was injected once into the tail artery with 0.4 mL each of (A) Cilastatin + D-Mannitol Mixture, (B) Iohexol, (C) Prepenem, and (D) embolization promoter (EGgel). Results: A visual inspection of the tail appearance of rats in each group was performed at 0, 3, 7, 15, and 21 days. At weeks 1 and 3, three rats per group were euthanized, and histopathological analyses were performed on the specimens obtained from each group. No significant differences were observed on day 7, but mild inflammation was observed in Group (D) on day 15. Histopathological inflammation scoring of tail central artery embolization was performed using a six-point scale (from 0 = absent to 5 = marked inflammation). Three groups were formed consisting of six male New Zealand white rabbits each: control, positive control, and test groups. The control group received an Iohexol injection (rabbits: 0.8 mL). The positive control and experimental groups were injected with prepenem and cilastatin/D-mannitol compound, respectively (0.8 mL), and vascular angiography was performed. The order of occlusion progression after embolization was as follows: test group, positive control group, and control group. Conclusions: We developed a cilastatin/D-mannitol compound that exhibits characteristics of short-term embolization by utilizing the pharmacokinetic properties of cilastatin and the crystalline material D-mannitol. We evaluated its particle size distribution microscopically, conducted histopathological evaluation including inflammation via animal experiments, and assessed the embolization effect.

Metallic and metallic oxide nanoparticles toxicity primarily targets the mitochondria of hepatocytes and renal cells.

Nanoparticles (NPs) are utilized in various applications, posing potential risks to human health, tissues, cells, and macromolecules. This study aimed to investigate the ultrastructural alterations in hepatocytes and renal tubular cells induced by metallic and metal oxide NPs. Adult healthy male Wistar albino rats (Rattus norvegicus) were divided into 6 (n = 7) control and 6 treated groups (n = 7). The rats in the treated groups exposed daily to silver NPs, gold NPs, zinc oxide NPs, silicon dioxide NPs, copper oxide NPs, and ferric oxide NPs for 35 days. The members of the control group for each corresponding NPs received the respective vehicle. Liver and kidney tissue blocks from all rats were processed for Transmission Electron Microscopy (TEM) examinations. The hepatocytes and renal tubular cells of all NPs-treated rats demonstrated mitochondrial ultrastructural alterations mainly cristolysis, swelling, membrane disruption, lucent matrices, matrices lysis, and electron-dense deposits. However, other organelles demonstrated injury but to a lesser extent in the form of shrunken nuclei, nuclear membrane indentation, endoplasmic reticulum fragmentation, cellular membranes enfolding, brush border microvilli disruption, lysosomal hyperplasia, ribosomes dropping, and peroxisome formation. One may conclude from the findings that the hepatocytes and the renal tubular cells mitochondria are the main targets for nanoparticles toxicity ending in mitochondrial disruption and cell injury. Further studies taking into account the relation of mitochondrial ultrastructural damage with a weakened antioxidant defense system induced by chronic exposure to nanomaterials are needed.