Sprague-Dawley Strain Research Articles

Role of Hypoxic Secretome from Mesenchymal Stem Cells in Enhancing Tissue Repair: Regulatory Effects on HIF-1α, VEGF, and Fibroblast in a Sphincterotomy Rat Model.

Fecal incontinence (FI) is the inability to control bowel movements, resulting in fecal leakage. If left untreated, FI can seriously impact the long-term well-being of individuals affected. Recently, using secretome has become a promising new treatment method. The secretome combines growth factors released outside cells during stem cell development, such as mesenchymal stem cells. It consists of soluble proteins, nucleic acids, fats, and extracellular vesicles, which contribute to different cell processes. The primary aim is to assess the impact of hypoxic secretome administration on accelerating wound healing through the HIF-1α pathway in a post-sphincterotomy rat model. The study was conducted with two distinct groups of 10 rats each, the control and treatment groups, which were injected with hypoxic secretome at 0.3 mL. The inclusion criteria for the rats were as follows: male gender, belonging to the Sprague-Dawley strain, aged between 12 to 16weeks, with an average body weight ranging from 240 to 250 grams. There was an increase in HIF-1α gene expression in both groups. The treatment group 37 was significantly higher on day 42 (p = 0.001). VEGF increased significantly in the treatment 38 group on day 42 (p = 0.015). The neovascularization score increased significantly in the treatment 39 group during the first 24hours (p = 0.004). The fibroblast score increased significantly in the 40 treatment group in the first 24hours (p = 0.000) and 42 days (p = 0.035). After being given secretome, there was a higher increase in % collagen area and collagen area (µm2) in the treatment group compared to the control group (27,77 vs 11.01) and (419.027,66 vs 186.694,16). The use of hypoxic secretome has a significant effect as a choice for the treatment of anal sphincter injury after sphincterotomy through the HIF-1α-VEGF-Fibroblast pathway.

Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis.

Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.

Comparative Cranial Geometric Morphometrics among Wistar Albino, Sprague Dawley, and WAG/Rij Rat Strains.

This research utilizes geometric morphometrics to investigate shape variation in the skull, mandible, and teeth among three rat strains: Wistar Albino (WA), Sprague Dawley (SD), and WAG/Rij (WR). Through the analysis of 48 rats using 2D geometric morphometric techniques, significant differences in their skull morphology were identified. This study indicates a shift from a rectangular to an oval cranial shape across strains, with notable size and morphological variances. Particularly, the WR strain's skull shape significantly differs from the SD and WA strains, suggesting distinct ecological or genetic pathways. Compared to the skull, mandible shape differences are less pronounced, but still significant. The WR strain exhibits a distinct mandible shape, potentially reflecting ecological adaptations like dietary habits. The teeth shape of WR rats is the most distinct. SD rats consistently exhibited larger sizes in both skull and mandible measurements, while WR rats were notably smaller. Interestingly, sexual dimorphism was not statistically significant in skull and teeth sizes, aligning with findings from previous studies. However, the mandible showed clear size differences between sexes, underscoring its potential for adaptive or behavioral studies. In summary, this study provides a comprehensive analysis of morphological variations in rat strains, highlighting the intricate interplay of size, shape, and ecological factors. These findings lay a foundation for deeper explorations into the adaptive, ecological, or genetic narratives influencing rat morphology.

Relationships between trace elements and cognitive and depressive behaviors in sprague dawley and wistar albino rats.

Introduction: This study investigates the effects of social isolation on mental health and cognitive functions in Sprague Dawley (SD) and Wistar Albino (WIS) rat strains, prompted by the heightened awareness of such impacts amid the COVID-19 pandemic. This study aims to explore the impact of social isolation on memory, learning, and behavioral changes in middle-aged SD and WIS rat strains and to investigate cortical trace element levels, seeking potential correlations between these levels and the observed behavioral responses to social isolation. Methods: Four groups of 14-month-old male rats were established: control and isolated SDs and WIS rats (CONT-SD, ISO-SD, CONT-WIS, ISO-WIS). Morris Water Maze and Porsolt Forced Swimming tests were conducted for behavioral assessment. Following behavioral tests, rats were sacrificed under general anesthesia, and cortices were isolated for analysis of macro and trace element levels (ICP/MS). Results: In behavioral tests, CONT-SD rats exhibited superior performance in the Morris Water Maze test compared to CONT-WIS rats, but displayed increased depressive behaviors following social isolation, as evident in the Porsolt Forced Swimming test (p < 0.05). ISO-SD rats showed elevated levels of Co and Cu, along with reduced levels of Cs and As, compared to ISO-WIS rats. Moreover, isolation resulted in decreased Cu and Mo levels but increased Rb levels in WIS rats. Comparison of trace element levels in naïve groups from different strains revealed lower Zn levels in the WIS group compared to SD rats. Discussion: The findings suggest that the SD strain learns faster, but is more susceptible to depression after isolation compared to the WIS strain. Increased Co and Cu levels in ISO-SD align with previous findings, indicating potential trace element involvement in stress responses. Understanding these mechanisms could pave the way for preventive treatment strategies or therapeutic targets against the consequences of stressors, contributing to research and measures promoting a balanced diet to mitigate neurobehavioral abnormalities associated with social isolation in the future.

Enhanced Ability of Agarwood Leaves (Aquilaria malaccensis Lam.) Ointment as Wound Healing to Heal Second-Degree Burns in Rats

Agarwood leaves (Aquilaria malaccensis Lam.) contain chemical substances such as alkaloids, flavonoids, and triterpenoids that contribute to the healing process of burns. This study aims to evaluate the wound healing activity of spray-dried extract from agarwood leaves formulated into an ointment for second-degree burns. The method involves extracting agarwood leaves through the decoction method, followed by spray drying, and subsequent evaluation of the extract. The prepared extract was then formulated into an ointment and tested for wound healing activity on 24 white rats of the Sprague-Dawley strain, divided into four groups, each consisting of 6 rats: negative control (ointment base), positive control (Betadine®), formula 1 (agarwood leaves extract ointment with 20% extract concentration - ALO-20), and formula 2 (agarwood leaves extract ointment with 30% extract concentration - ALO-30). Second-degree burns were induced by exposing the rats' backs to ferrous metal for 3 seconds and treating them for 14 days. Observations were made by assessing changes in burn diameter and scab formation. In this study, ALO-30 demonstrated superior activity. Scab formation was faster on day 3, and the burn diameter was reduced by day 7. The results indicated that ALO-30 led to a quicker reduction in wound diameter compared to ALO-20 and the negative control. Agarwood leaves extract ointment with a concentration of 30% (ALO-30) exhibited a more effective wound healing effect than the ointment with a 20% concentration (ALO-20).

Enhanced Fibrogenesis Activity in Diabetic Wound Using 20% Anredera scandens (L.) Moq. Leaves Extract Ointment in Sprague dawley Rats

Background: In diabetic conditions, decreased glucose-6-phosphate dehydrogenase activity results in reduced nitric oxide synthesis. Reduced nitric oxide synthesis results in the production of ROS. This may impede the processes of angiogenesis and vasoconstriction and prolong inflammation. Objective: We were interested in investigating the mechanism by which 20% of Anredera scandens leaves extract ointment increases fibrogenesis activity because this condition can affect the development of damaged skin tissue. This study's design is a post-test-only laboratory experiment. Material and methods: The study employed male Sprague dawley strain rats that were induced with 40 mg/kgBW of STZ. The mice were divided into four groups: the negative group (which got diabetic wounds only), the positive group (which got Gentamicin ointment), and the test group (which got 20% extract ointment). Results: The skin tissue from each group was then examined histopathologically. After receiving 20% ointment of Anredera scandens leaves extract, the test group's mean fibrogenesis histopathology score on day 14 was significantly higher (P=0.022) at 3.75 than that of the negative group, which had a mean score of 2.75. Following that, the skin tissue of both the extract test group and the normal group was examined histopathologically. In comparison to the normal group mean score of 4.0 on day 14, the test group, which received 20% ointment of Anredera scandens leaves extract, had a non-significant (P=0.317) mean fibrogenesis histopathology score of 3.75. Subsequently, skin tissue was examined histopathologically for both the positive and normal groups. According to the results, on day 14, the positive group's average fibrogenesis histopathology score was 3.5, while the normal group's average score was 4.0. This difference was not statistically significant (P=0.127). Conclusions: Thus, it can be said that 20% Anredera scandens leaf extract ointment is comparable to gentamicin ointment in its capacity to promote fibrogenesis activity in diabetic wounds.

Brca2(p.T1942fs/+) dissipates ovarian reserve in rats through oxidative stress in follicular granulosa cells

Pathogenic variants of BRCA1/2 constitute hereditary breast and ovarian cancer (HBOC) syndrome, and BRCA1/2 mutant is a risk for various cancers. Whereas the clinical guideline for HBOC patients has been organized for the therapy and prevention of cancer, there is no recommendation on the female reproductive discipline. Indeed, the role of BRCA1/2 pathogenic variants in ovarian reserve has not been established due to the deficiency of appropriate animal models. Here, we used a rat model of Brca2(p.T1942fs/+) mutant of Sprague-Dawley strain with CRISPR-Cas9 editing to evaluate ovarian reserve in females. Fertility and ovarian follicles were evaluated and anti-Müllerian hormone (AMH) was measured at 8–32 weeks of age with a comparison between the wild-type and the mutant rats (MUT). MUT revealed a significantly smaller number of deliveries with fewer total pups. Furthermore, MUT showed a significant decrease in primordial follicles at 20 weeks and a low AMH level at 28 weeks. RNA-sequencing of the ovary at 10 weeks detected acceleration of the DNA damage repair pathway, which was accompanied by oxidative stress-induced DNA double-strand breaks, a decrease in PTEN, and an increase in mTOR in follicular granulosa cells. In conclusion, Brca2(p.T1942fs/+) dissipates primordial follicles via early activation of granulosa cells through oxidative stress, leading to earlier termination of fertility.

Long exposure to a mixture of endocrine disruptors prediposes the ventral prostate of rats to preneoplastic lesions.

Endocrine disruptors (ED) are compounds dispersed in the environment that modify hormone biosynthesis, affecting hormone-dependent organs such as the prostate. Studies have only focused on evaluating the effects of ED alone or in small groups and short intervals and have not adequately portrayed human exposure. Therefore, we characterized the prostate histoarchitecture of rats exposed to an ED mixture (ED Mix) mimicking human exposure. Pregnant females of the Sprague-Dawley strain were randomly distributed into two experimental groups: Control group (vehicle: corn oil, by gavage) and ED Mix group: received 32.11mg/kg/day of the ED mixture diluted in corn oil (2ml/kg), by gavage, from gestational day 7 (DG7) to post-natal day 21 (DPN21). After weaning at DPN22, the male pups continued to receive the complete DE mixture until they were 220days old when they were euthanized. The ED Mix decreased the epithelial compartment, increased the fractal dimension, and decreased glandular dilation. In addition, low-grade prostatic intraepithelial neoplasia was observed in addition to regions of epithelial atrophy in the group exposed to the ED Mix. Exposure to the mixture decreased both types I and III collagen area in the stroma. We concluded that the ED Mix was able to cause alterations in the prostatic histoarchitecture and induce the appearance of preneoplastic lesions.

Evaluation of the Antithrombotic Activity of Acmella oleracea L. Flower Ethanol Extract

Acmella oleracea L. (hereinafter abbreviated as AOE) is one of the plants with the potential for antithrombosis, one of the deadliest cardiovascular diseases in Indonesia. The antithrombotic activity test on AOE leaf extract revealed that it could lyse blood clots. However, no information regarding the AOE flower as an antithrombosis is provided. This study, thus, aims to determine the chromatography profile and the antithrombotic activity of the AOE flower ethanol extract. To identify the AOE chemical profile, thin-layer chromatography was carried out. Antithrombotic testing was performed on male rats of the Sprague-Dawley strain. Then, the antithrombotic activity was tested using the FeCl3-induced rat method, with the observed parameter being total occlusion time. The test animals were also divided into six groups: normal, solvent (CMC-Na 0.9%), comparator drug (clopidogrel 8.67 mg/kg), and AOE (doses 125, 250, and 375 mg/kg). The data obtained were then analyzed statistically using Kruskal-Wallis, followed by Tukey's. The TLC profile results confirmed the presence of the alkaloid compound in AOE. The authors also found that AOE at doses of 125, 250, and 375 mg/kg significantly prolonged the occlusion time comparable to that of clopidogrel at 8.67 mg/kg (p 0.05). This finding indicates that AOE has antithrombotic activity in FeCl3-induced rats.

Sprague Dawley rats from different vendors vary in the modulation of prepulse inhibition of startle (PPI) by dopamine, acetylcholine, and glutamate drugs

RationaleRodent vendors are often utilized interchangeably, assuming that the phenotype of a given strain remains standardized between colonies. Several studies, however, have found significant behavioral and physiological differences between Sprague Dawley (SD) rats from separate vendors. Prepulse inhibition of startle (PPI), a form of sensorimotor gating in which a low-intensity leading stimulus reduces the startle response to a subsequent stimulus, may also vary by vendor. Differences in PPI between rat strains are well known, but divergence between colonies within the SD strain lacks thorough examination.ObjectivesWe explored intrastrain variation in PPI by testing SD rats from two vendors: Envigo and Charles River (CR).MethodsWe selected drugs acting on four major neurotransmitter systems that have been repeatedly shown to modulate PPI: dopamine (apomorphine; 0.5, 1.5, 3.0 mg/kg), acetylcholine (scopolamine; 0.1, 0.5, 1.0 mg/kg), glutamate (dizocilpine; 0.5, 1.5, 2.5 mg/kg), and serotonin (2,5-Dimethoxy-4-iodoamphetamine, DOI; 0.25, 0.5, 1.0 mg/kg). We determined PPI and startle amplitude for each drug in male and female Envigo and CR SD rats.ResultsSD rats from Envigo showed dose-dependent decreases in PPI after apomorphine, scopolamine, or dizocilpine administration, without significant effects on startle amplitude. SD rats from CR were less sensitive to modulation of PPI and/or more sensitive to modulation of startle amplitude, across the three drugs.ConclusionsSD rats showed vendor differences in sensitivity to pharmacological modulation of PPI and startle. We encourage researchers to sample rats from separate vendors before experimentation to identify the most suited source of subjects for their specific endpoints.

The relationship between AQP1 expression in the subventricular zone and severity of hydrocephalus in Rattus Norvegicus strain Sprague-Dawley rats

Link of Video Abstract: https://youtu.be/pWRyUuqXX7g Background: Hydrocephalus is a condition of dilation of the ventricles caused by disturbances production, distribution, or absorption of cerebrospinal fluid (CSF). One of the integral membrane proteins identified in facilitating water transport across the plasma membrane is aquaporin-1 (AQP1), which is frequently found in the plexus choroid. However, theoretically also transports water to the subventricular zone (SVZ) with an unknown mechanism. AQP1 expression will be raised in SVZ under hydrocephalus conditions. This study aims to evaluate the relationship between the severity of hydrocephalus and AQP1 levels in SVZ. Methods: This research was conducted in an experimental design using Rattus Norvegicus rats of the Sprague-Dawley strain, which were injected with kaolin to create a hydrocephalus model. The study included 24 rats, divided into four groups of six each: the control group and the hydrocephalus induction group on day 7, day 14, and day 21. AQP1 expression was observed using immunohistochemical staining and counted semi-quantitatively. Results: The average AQP1 expression increased with observation time in the rat model in each group. The ANOVA test showed a significant difference between the four study groups (p=0.001). The correlation showed a statistically significant difference (p=0.000). The results showed an increased expression of the SVZ with a higher severity of hydrocephalus. Conclusion: The severity of hydrocephalus and AQP1 levels in SVZ are correlated, with the latter being higher, the more severe the degree of hydrocephalus.

Three levels of enhanced inspired CO2 or fasted-state on stress response activation in behaviorally inhibited humans and rats

Behavioral inhibition (BI) is believed to be a genetically determined trait that affects roughly 33% of the human population. These individuals tend to respond to stressful situations differently than their non-behaviorally inhibited (NBI) counterparts. In the rodent population, a similar behavioral/stress model exists. The Sprague-Dawley (SD) strain often acts as a “control” among rat strains and can be considered to be the rat equivalent to NBI individuals, and the Wistar-Kyoto (WKY) strain is the rodent equivalent to BI individuals. The differences in the activation of the sympathetic nervous system between chronically stressed and non-stressed populations remain unknown. Our current study tested the hypothesis BI individuals and WKY rats will have increased stress responses. In humans, we tested physiological responses to increasing levels of carbon dioxide (CO2) through analyses of breathing, heart rate, and blood pressure. The Adult Measure of Behavioral Inhibition (AMBI) survey was used to determine the presence of BI. A 15-minute control period baseline was completed followed by an acquisition period of five minutes of each 3%, 5%, and 7% CO2, respectively. Preliminary results were analyzed through a CO2 sensitivity slope (inspired minute ventilation ((L/min) / end-tidal CO2) and show that BI individuals had increased, exaggerated responses to the respiratory stressors across the three levels of enhanced CO2. In the rodent model, signaled lever-press avoidance was used to examine the activation of stress responses. Rats were trained to avoid mild foot shock using a tone warning signal. As demonstrated previously, WKY rats acquired a higher level of avoidance responses. Rats were then food-deprived overnight and subsequently retested on signal lever-press avoidance. Food deprivation did not affect the high rate of avoidance seen in WKY rats; however, food deprivation increased the SD rate of avoidance to nearly the level of WKY rats. Our data suggest that WKY rats do not respond to food deprivation when paired with lever-press avoidance; however, SD rats do. Simply, the addition of a stressor causes SD rats to behave more similarly to their WKY counterparts. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Amphotericin B Pharmacokinetics: Inter-strain Differences in Rats Following Intravenous Administration of the Most Commonly Marketed Formulations of the Drug.

Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity. Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug. Twenty-four Wistar and Sprague-Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method. Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain. Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

Rhizophora apiculata Bark Ethanolic Extracts Prevent Kidney Damage Caused by Cigarette Smoke in Male Rats

Rhizophora apiculata mangrove bark contains high levels of antioxidants, including triterpenoids, steroids, saponins, and tannins. The high antioxidant content can prevent oxidative stress, one of which is caused by free radicals from cigarette smoke. This research aimed to determine the potential of Rhizophora apiculata mangrove bark to protect against damage to the kidney organs of male white rats (Rattus novergicus) of the Sprague-Dawley strain exposed to cigarette smoke. This study used 25 mice divided into 5 groups for 30 days, namely group K(-), which was not given exposure to cigarette smoke and mangrove bark extract; group K(+), which was only given exposure to cigarette smoke; group P1, which was given the extract mangrove bark with a dose of 26.27 mg/kg BW and given exposure to cigarette smoke 24 cigarettes per day, group P2 which was given mangrove bark extract with a dose of 56.55 mg/kg BW and given exposure to cigarette smoke 24 cigarettes per day, and group P3 which was given mangrove oil bark extract at a dose of 113.1 mg/kg BW and given exposure to cigarette smoke 24 cigarettes per day. On day 31, the rats were euthanized, and their kidneys were prepared for histology. Kidney histology was observed, and kidney damage was assessed from the histology of glomerular and renal tubular damage. The kidney damage score is 0 if there was no damage, 1 if inflammatory cell infiltration was found, 2 if Bowman space edema or swelling of tubular epithelial cells was found, 3 if necrosis was found. Then, take the average of each renal tubular and glomerular damage score and add them together for a total damage score, namely 0-6. The median kidney damage score in the K (-) group was 0.4, the K (+) group was 3.6, the P1 group was 2.4, the P2 group was 2.4, and the P3 group was 2.2. The results of the Kruskal-Wallis test obtained a p-value of 0.001, meaning there were significant differences in at least the two treatment groups. This research showed that administering Rhizophora apiculata mangrove bark extract could prevent histological damage to the kidneys of male white rats of the Sprague-Dawley strain caused by cigarette smoke.

Molecular Mechanism for Hepatic Glycerolipid Partitioning of n-6/n-3 Fatty Acid Ratio in an Obese Animal Biomodels.

The n-6/n-3 metabolic pathway associated with hepatic glycerolipid portioning plays a key role in preventing obesity. In this nutrition metabolism study, we used in vivo monitoring techniques with 40 obese male Sprague-Dawley strain rats attached with jugular-vein cannula after obesity was induced by a high-fat diet to determine the molecular mechanism associated with hepatic glycerolipid partitioning involving the n-6/n-3 metabolic pathway. Rats were randomly assigned to four groups (10 animals per group), including one control group (CON, n-6/n-3 of 71:1) and three treatment groups (n-6/n-3 of 4:1, 15:1 and 30:1). They were fed with experimental diets for 60 days. Incorporation rates of [14C]-labeling lipid into glycerolipid in the liver were 28.87-37.03% in treatment groups fed with diets containing an n-6/n-3 ratio of 4:1, 15:1 and 30:1, which were significantly (p &lt; 0.05) lower than that in the CON (40.01%). However, 14CO2 emission % of absorbed dose showed the opposite trend. It was significantly (p &lt; 0.05) higher in a treatment groups (n-6/n-3 of 4:1, 15:1 and 30:1, 30.35-45.08%) than in CON (27.71%). Regarding the metabolic distribution of glycerolipid to blood from livers, phospholipid/total glycerolipid (%) was significantly (p &lt; 0.05) lower in CON at 11.04% than in treatment groups at 18.15% to 25.15%. Moreover, 14CO2/[14C]-total glycerolipid (%) was significantly (p &lt; 0.05) higher in treatment groups at 44.16-78.50% than in CON at 39.50%. Metabolic distribution of fatty acyl moieties flux for oxidation and glycerolipid synthesis in the liver were significantly (p &lt; 0.05) better in order of 4:1 &gt; 15:1 &gt; 30:1 than in the CON. Our data demonstrate that n-6/n-3 of 4:1 could help prevent obesity by controlling the mechanism of hepatic partitioning through oxidation and esterification of glycerolipid in an obese animal biomodel.

Asymmetric Dimethylarginine in an NMU-induced Rat Mammary Tumor Model.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) production and a newly discovered risk factor involved in endothelial dysfunction and adverse cardiovascular events. Recently, both NO and ADMA have also emerged as molecules of interest in carcinogenesis and tumor growth progression. Our earlier studies have confirmed elevated plasma ADMA levels in patients with hematological malignancies. However, the cause of elevated ADMA was unclear. The aim of this study was to assess the concentrations of ADMA, symmetric dimethylarginine (SDMA) and L-arginine in rats exposed to N-nitroso-N-methylurea (NMU) for the induction of mammary tumors. A total of 95 female rats of the Sprague-Dawley strain were used in the study. Plasma concentrations of ADMA, SDMA and L-arginine were quantified and statistically analyzed. Mean ADMA levels were higher in the tumor-bearing group compared to the control group. Mean plasma levels of SDMA and L-Arginine were not significantly different between the groups. The L-ARG/ADMA ratio was lower in rats with tumors compared to controls. Histological assessment confirmed expression of ADMA within the tumor cells, which strongly suggests that these tumor cells were the source of ADMA. Other studies are warranted to further explain the role of ADMA in neoplastic diseases.

Uji UJI EFEKTIVITAS GEL EKSTRAK ETANOL 70% GETAH GAMBIR (Uncaria gambir. Roxb) dan BETADINE TERHADAP LUKA SAYAT PADA TIKUS PUTIH JANTAN (Rattus norvegicus) GALUR

Gambir (Uncaria gambir. Roxb) contains flavonoids, tannins, saponins and alkaloids that can help heal wounds. One of the main ingredients that gambir contains is catechins . Catechins are flavonoid compounds with anti-inflammatory, antioxidant and antibacterial properties derived from Gambir. This study aimed to compare wound healing time between ethanolic extracts of 70% gambir resin gel (Uncaria gambir. Roxb) with betadin preparations in male Sprague dawley rats (Rattus norvegicus). A total of 9 white rats (Rattus norvegicus) strain Sprague dawley were divided into 3 groups, a negative control group for gel base treatment and a positive control group for gambir sap gel preparations (Uncaria gambir. Roxb) betadine comparison group. This study was conducted by experimental method with a post-trial controlled group design. Each group is colored with group preparations, the treatment is carried out 3 × 1 every day. Wound healing time was analyzed by a one-way Anova test on spss. Healing ingroup I was 10.6 days, in group II, 10.3 days in group III and 9.3 days.

Bioactive role of aqueous extract of aegle marmelos leaves on obese rats

The aim of this study was to evaluate the effect of Aegle marmelos aqueous extract (AMAE) leaves on obese rats. Twenty-five adult male albino rats (Sprague-Dawley strain), weighing about (200±10g) were divided randomly into two main groups as follow: the first group (-Ve control= 5 rats) was fed on basal diet. The second group (20 rats) was fed on high fat diet (HFD) for 4 weeks then divided equally to 4 groups from group 2 to group 5. Group 2 (+Ve control) fed on basal diet. Group 3, 4 and 5 fed on HDF administrated orally with 1, 2 and 3 ml of AMAE, respectively. At the end of the experimental period (4 weeks), rats were scarified and serum was collected to determine levels of lipid profile, glucose, leptin kidneys and liver functions. The results showed that the body weight of rats and serum levels of lipids profile, leptin, glucose, kidneys functions and liver enzymes were elevated by HFD administration (positive control group) compared with negative control group, while HDL-C decreased. It was also found that oral administration of AMAE diet with reversed these changes that caused by HFD.

Effects of Amnion Lyophilization Sterile Radiation on Vascular Endothelial Growth Factor and Cluster of Differentiation 34 in Nonunion Fractures

One of the causes of nonunion is inadequate vascularization due to severe injury mechanisms that cause defective bone healing factors. Therefore, in non-union fractures, a trigger is needed for the growth factors to work properly. This study aimed to determine the effects of ALSR on VEGF and CD-34 in non-union fractures. This study used an experimental post-test only control group design that involved white rats of the Sprague-Dawley strain. The VEGF expression was assessed by anti-VEGF staining, which was done by cutting paraffin blocks into a thickness of 5 μm, then the blocks were deparaffinized in xylol and rehydrated with alcohol. The results of the analysis are displayed with their mean ranks between control groups and treatment groups. It was found that CD-34 expression was high in the ALSR group. This shows the occurrence of angiogenesis and the regeneration in the case of non-union fractures in this study.

Mechanism of Apoptosis Retinal Ganglion Cells Rattus norvegicus Caused by Ethambutol

Background: The cause of cell death is thought to be due to the pathological apoptotic process in Retinal Ganglion Cells (RGCs), but how the exact mechanism of what is most influential is still not explained. Objective: This study aimed to explain the mechanism of RGCs apoptosis Rattus Norvegicus which is thought to underlie the occurrence of ethambutol toxic optic neuropathy. Methods: A total of 42 male, adult Rattus norvegicus Sprague-Dawley strains were divided into 6 groups with 3 control groups and 3 treatment groups in a randomized design with time series test. The treatment groups were given ethambutol 15 mg/kg/day for each group within 5, 10 and 15 days orally using a gauge.Expressions of SOD2, MDA, PKC δ, p53, Cyt c, Caspase 3 and apoptosis were examined by immunohistochemical methods. Results: Ethambutol affected significant decreased expression of SOD2 with p=0.002 in 5 days, p=0.013 in 10 days and p=0.018 in 15 days; significant increased MDA in 5 days with p=0.05, 10 days with p=0.017, 15 days with p=0.002; significant increased p53 in 5 days with p=0.012, 10 days with p=0.002, 15 days with p=0.001; significant increased Cyt c in 5 days with p=0.004, 10 days with p=0.001, 15 days with p=0.001; significant increased Caspase 3 in 5 days with p=0.001, 10 days with p=0.003, 15 days with p=0.001 and apoptosis in 5 days with p=0.001, 10 days with p=0.001, 15 days with p=0.001. Conclusion: The mechanism of apoptosis of RGCs caused by ethambutol was showed via decreased expression SOD2, increased expression of MDA, p 53, Cyt c, Caspase 3 andapoptosis. These biomarkers are essential to detect apoptosis as one of mechanism in cell death.