Contraction In Rats Research Articles

In Vitro and In Vivo Evaluation of Electrospun PVA Nanofiber Containing ZnO/Curcumin for Wound Healing Application.

The development of biocompatible wound dressings containing therapeutic agents to accelerate wound healing is an interesting field of study in biomedical sciences. Polyvinyl alcohol (PVA) nanofibers were loaded with zinc oxide nanoparticles (ZnO NPs) and curcumin (Cur) through electrospinning. Thedressings were characterized by SEM and XRD and FTIR. The antioxidant, antibacterial, and cytotoxic activities Cur/ZnO/PVA nanodressing were evaluated using DPPH radical scavenging assay, disc diffusion method, and MTT assay, respectively. Cur/ZnO/PVA nanodressing showed sustained Cur release about 19.7% and 61.1% after 8h and 168h, respectively. Cur/ZnO NPs/PVA mixture had higher antioxidant potential than PVA, ZnO NPs, and Cur. The dressing showed a good antibacterial effect. The in vivo wound healing effect of different types of prepared dressings, includingPVA, Cur/PVA,Cur/ZnO/PVA, and ZnO/PVAnanofibers, was also investigated. PVA dressing containing Cur/ZnO NPs resulted in the highestincrease of wound contraction in rats. The assembly of Cur and ZnO NPs on PVA nanofibers could propose as an effective delivery method toimprovethe wound healing process. The investigated wound dressing could be commercialized and used on a large scale after proper further studies, including clinical trials.

Does Sertraline Affect Contraction in Endothelium Damaged Aorta

Aim: Selective Serotonin Reuptake Inhibitor (SSRI) group antidepressants are frequently used in heart patients. In the study, we aimed to investigate the effects of sertraline (SE) on aortic contraction on healthy/damaged rat aorta. Materials and Methods: Wistar albino rats (24) were divided into group1-aorta-intact endothelium and group2-aorta-damaged endothelium. The isolated aortic tissues were placed in organ baths. Changes in the isometric tension of the aortic rings were recorded. Contractions were recorded in both groups after the application of phenylephrine (PE 10-6M). Afterwards, cumulative sertraline (SE 50 mg) (10-9-10-4M) was given to group 1. In Group 2, to control aortic endothelial damage, acetylcholine (10-6M) was applied and the tissues were washed for an hour, the second dose of PE was given, then SE was given cumulatively (10-9-10-4M), and contractions were recorded. Results: After cumulative SE (10-9-10-4M) was given to Group 1, a significant inhibition in spontaneous contractions was detected in the first three sertraline doses (10-9,10-8,10-7)(p<0.05), and in the remaining sertraline doses contraction inhibition continued. When comparing SE 10 6,-5,-4 and 10-9,-8,-7 doses, there was inhibition of contractions (p<0.005). In group2, the inhibition of second PE contractions continued after sertraline doses, but the inhibition was observed less than in group1 (p<0.05). Conclusion: SE inhibited PE-induced smooth muscle contraction in rat isolated aorta. PE-induced smooth muscle contractions were inhibited more slowly in the endothelium-damaged aorta. It is thought that NO release and NO-dependent vasodilation in the aorta decrease as a result of damage. A clearer understanding of the effects of sertraline on the cardiovascular system will be possible with further research. Keywords: Aorta, endothelium, sertraline, contraction, vasorelaxation

Ранні маркери гострої доксорубіциніндукованої кардіотоксичності та механізми її розвитку

Arrhythmias and congestive heart failure, which pose the greatest risk of toxic cardiomyopathy, are the clinically limiting side effects of doxorubicin, the main highly active anticancer agent. The difficulty of early diagnosis of cardiomyopathy and timely detection of cardiac dysfunction associated with chemotherapy remains a significant medical problem. The aim of our study was to identify early signs of acute doxorubicin-induced cardiotoxicity in adult rats by assessing ECG changes and biochemical parameters. Acute cardiotoxicity was modelled by short-term intraperitoneal injection of doxorubicin at a total dose of 15 mg/kg. On the 5th day of the experiment, visual fluctuations of electrocardiogram (ECG) waveforms, duration and amplitude of the main teeth and intervals, as well as heart rate (HR) in the control and experimental groups of rats were studied to determine early ECG signs of cardiotoxicity. The most significant ECG changes were a doubling of the QT interval duration and significant ST-segment elevation in the rats of the experimental group. In experiments on isolated aortic rings, we demonstrated doxorubicin-induced disruption of both vascular relaxation and contraction mechanisms. The endothelium-dependent relaxation of vascular preparations of animals after administration of doxorubicin to acetylcholine (0.1 μmol/l) was 47% less than in the control group. The vascular ring contractions in rats under the influence of norepinephrine (10 μmol/l) were 59% lower than in control rats. After doxorubicin administration, oxidative stress developed against the background of cardiovascular disorders. Thus, the content of diene conjugates and malondialdehyde increased by 4 and 2.5 times, respectively. At the same time, in isolated cardiac mitochondria, the activity of inducible NO synthase increased 3.7-fold with a simultaneous significant 4.8-fold inhibition of constitutive NO synthase. An increase in the content of acute-phase biochemical parameters that are markers of damage, namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase myocardial fraction (CPK MB) by 2.2, 1.4 and 1.5 times, respectively, was detected. Thus, the acute cardiotoxic effect of doxorubicin results in changes in the systolic-diastolic function of the left ventricle of the heart and its conduction, automaticity and contractility, as well as impaired relaxation and contraction of isolated preparations of the aorta against the background of increased activity of inducible and decreased constitutive NO synthesis, accompanied by oxidative stress and increased content of biochemical markers of myocardial damage.

Chemical characterization, anti-struvite crystal, anti-inflammatory, analgesic, and antidepressant activities of Papaver rhoeas L. root and leaf extracts

Ethnopharmacological relevancePapaver rhoeas L. (P. rhoeas) is used to treat a wide range of pathologies. But there is no data on the anti-struvite, anti-inflammatory, analgesic, and anti-depressant effects of root and leaf extracts from this medicinal plant.Aim of the study: This study aimed to chemically characterize and determine the antidepressant, analgesic, anti-inflammatory, and anti-struvite activities of the root extract (RE) and leaf extract (LE) of P. rhoeas, a wild plant. Materials and methodsThe extraction of secondary metabolites and phytochemical screening were carried out using standard methods. The anti-struvite effect of our samples was assessed by Fourier transform infrared spectroscopy (FT-IR) and microscopic observation. For the anti-inflammatory impact, we used the carrageenan-induced paw edema technique in rats. To assess the analgesic effect of the extracts, we recorded the resulting abdominal contraction after intraperitoneal (IP) acetic acid injection. Finally, we assessed the antidepressant effect by conducting the Forced Swimming Test (FST). ResultsPhytochemical screening results revealed the presence of phenols, flavonoids, saponins, tannins, coumarins, terpenoids, and alkaloids. Extraction results confirmed that our extracts were rich in secondary metabolites. Both P. rhoeas extracts limited struvite crystal development by reducing the size and number of crystals, as indicated by FT-IR analysis and microscopic observation. Additionally, the anti-struvite effects of the LE sample were greater than those of the RE sample. The results of the anti-inflammatory capacity of our extracts demonstrate the maximum inhibition of carrageenan-induced edema following 6 h (T6) of injection, ranging from 72.73 ± 7.7% for LE (400 mg/kg) to 95.45 ± 6.42% for the RE sample (400 mg/kg). On the other hand, the results for analgesic activity showed that the number of abdominal contractions in rats treated with RE and LE ranged from 11 ± 1.73 for RE (400 mg/kg) to 18 ± 1.50 for LE (200 mg/kg), while that of aspirin was 10.33 ± 0.57. Furthermore, the FST results show that the immobility time in rats treated with RE and LE varied from 91.98 ± 4.24 s for LE-treated rats (300 mg/kg) to 123.54 ± 7.83 s for RE-treated rats (150 mg/kg). ConclusionBased on these results, the roots and leaves of the studied plant can be considered a significant source of biologically active molecules for use in the pharmaceutical industry.

Invasive dynamic electrical impedance myography during 100s of moderate contraction in rats' gastrocnemius muscle.

The present study aimed to investigate the behavior of dynamic electrical impedance myography (dEIM) signals during a 100-s period of the dynamic contraction of Wistar rats' gastrocnemius evoked by electrical stimulation and to link the variations in bioimpedance with muscular energy systems. Muscle contraction used 30% of the maximum muscular force and persisted for 100s, along which dynamic bioimpedance signals were acquired. Based on the bioimpedance signals, two parameters, ΔZc and ΔZpc, were calculated to allow the analysis of their changes with the energy systems that supplied adenosine triphosphate (ATP) to the muscle. ΔZc indicated the variation of impedance of a twitch cycle compared to the values observed during the rest period preceding the cycle, and ΔZpc indicated slow bioimpedance variations compared to the values obtained during the rest period. The results indicated that ΔZc followed the force behavior, achieving a change rate of ∼14%. This parameter was associated with instantaneous impedance changes owing to the occurrence of each twitch. Although the findings of this study were linked to energy system processes, future studies are required for improving the understanding of the underlying mechanisms involved in dEIM. The results contributed to understanding the relation of energy systems that supply ATP to the muscles with dEIM variations that occurred during muscle activity.

Effectiveness of collagen and gatifloxacin in improving the healing and antibacterial activities of gellan gum hydrogel films as dressing materials

The demand for advanced wound care products is rapidly increasing nowadays. In this study, gellan gum/collagen (GG/C) hydrogel films containing gatifloxacin (GAT) were developed to investigate their properties as wound dressing materials. ATR-FTIR, swelling, water content, water vapor transmission rate (WVTR), and thermal properties were investigated. The mechanical properties of the materials were tested in dry and wet conditions to understand the performance of the materials after exposure to wound exudate. Drug release by Franz diffusion was measured with all samples showing 100 % cumulative drug release after 40 min. Strong antibacterial activities against Staphylococcus aureus and Staphylococcus epidermis were observed for Gram-positive bacteria, while Escherichia coli and Pseudomonas aeruginosa were observed for Gram-negative bacteria. The in-vivo cytotoxicity of GG/C-GAT was assessed by wound contraction in rats, which was 95 % for GG/C-GAT01. Hematoxylin and eosin and Masson's trichrome staining revealed the appearance of fresh full epidermis and granulation tissue, indicating that all wounds had passed through the proliferation phase. The results demonstrate the promising properties of the materials to be used as dressing materials.

Design and evaluation of sodium alginate-based hydrogel dressings containing Betula utilis extract for cutaneous wound healing.

Traditional wound dressings have a limited capacity to absorb exudates, are permeable to microbes, and may adhere to wounds, which leads to secondary injuries. Hydrogels are promising alternative dressings to overcome the above challenges. In this study, we developed sodium alginate-based hydrogel films loaded with Betula utilis bark extract. These films were prepared via solvent-casting crosslinking method and evaluated for wound healing activity. Prepared films were 0.05-0.083mm thick, flexible with folding endurance ranging from 197-203 folds, which indicates good physical properties. Optimized formulations exhibited successful loading of extract in the film matrix without any interaction as confirmed by FTIR. Maximum zone of inhibition against Gram-positive and Gram-negative bacteria was achieved by optimum formulation (B6), i.e., 19mm and 9mm, respectively, with > 90% scavenging activity. Furthermore, this optimum formulation (B6) was able to achieve 93% wound contraction in rats. Histograms of the optimized formulation treated group also revealed complete reepithelization of wounds. Conclusively, our extract-loaded hydrogel dressing successfully demonstrated its potential for cutaneous wound healing.

Modulation of Melatonin Receptors Regulates Reproductive Physiology: The Impact of Agomelatine on the Estrus Cycle, Gestation, Offspring, and Uterine Contractions in Rats

Agomelatine is a pharmaceutical compound that functions as an agonist for melatonin receptors, with a particular affinity for the MT1 and MT2 receptor subtypes. Its mode of action is integral to the regulation of diverse physiological processes, encompassing the orchestration of circadian rhythms, sleep-wake cycles, and mood modulation. In the present study, we delve into the intricate interplay between agomelatine and the modulation of estrus cycles, gestation periods, offspring numbers, and uterine contractions, shedding light on their collective impact on reproductive physiology. Both in vivo and in vitro experiments were performed. Wistar Albino rats, divided into four groups: two non-pregnant groups (D1 and D2) and two pregnant groups (G1 and G2). The D1 and G1 groups served as control groups, while the D2 and G2 groups received chronic agomelatine administration (10 mg/kg). Uterine contractions were assessed in vitro using myometrial strips. Luzindole, a melatonin receptor antagonist, was employed to investigate the pathway mediating agomelatine's effects on uterine contractions. In in vivo studies, chronic agomelatine administration extended the diestrus phase (p<0.05) in non-pregnant rats, prolonged the gestational period (p<0.01), and increased the fetal count (p<0.01) in pregnant rats. Additionally, agomelatine reduced plasma oxytocin and prostoglandin-E levels (p<0.01) during pregnancy. In vitro experiments showed that agomelatine dose-dependently inhibited spontaneous and oxytocin-induced myometrial contractions. Luzindole (2 µM) reverse the agomelatine-induced inhibition of myometrial contractions. These findings suggest that agomelatine holds the potential to modulate diverse reproductive parameters during the gestational period, influencing estrus cycling, gestational progression, offspring development, and the orchestration of uterine contractions.

Exaggerated blood pressure response to static exercise in hindlimb ischemia-reperfusion.

Peripheral artery disease (PAD) reduces the blood flow supply in the affected limbs as one of the significant cardiovascular concerns. Revascularization surgery in the femoral artery plays a central role in treating PAD. Exercise is also a rehabilitation strategy suggested for PAD patients to improve vascular functions. However, the effects of limb ischemia-reperfusion (IR), one of the most predominant complications in revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. In the present study, we determined 1) the blood flow status in the hindlimb muscles of rats (plantar muscle, red and white portions of gastrocnemius) with different time points of the hindlimb IR; and 2) the BP response to static muscle contraction in rats at different time points after the blood flow reperfusion procedure. Results of this study indicated that, compared with the Sham group, the blood flow in the hindlimb muscles evaluated by Evans blue concentration was significantly reduced at 6h of femoral artery occlusion (FAO 6h) (vs. sham control, p < 0.05). The decreased blood flow was gradually recovered after the blood flow reperfusion for 18 (IR 18h), 66 (IR 66h), and 114 (IR 114h) hours (p < 0.05 vs. FAO 6h for all IR groups). The response of mean arterial pressure was 20 ± 4mmHg in Sham rats (n = 7); 32 ± 10mmHg in IR 18h rats (n = 10); 27 ± 7mmHg in IR 66h rats (n = 13); 26 ± 4mmHg in IR 114h rats (n = 9) (p < 0.05 vs. Sham for all groups). No significant difference was observed in the peak-developed tension during muscle contraction among all the groups (p > 0.05). In conclusion, static exercise-induced BP response is exaggerated following IR. Whereas the BP response is not statistically significant but tends to decrease with a prolonged IR time, the exaggerated BP response remains through time points from post-IR 18h-114h.

Effect of 40 Hz Magnetic Field Application in Posttraumatic Muscular Atrophy Development on Muscle Mass and Contractions in Rats

Muscle atrophy refers to the deterioration of muscle tissue due to a long-term decrease in muscle function. In the present study, we simulated rectus femoris muscle atrophy experimentally and investigated the effect of pulsed electromagnetic field (PEMF) application on the atrophy development through muscle mass, maximal contraction force, and contraction-relaxation time. A quadriceps tendon rupture with a total tenotomy was created on the rats' hind limbs, inhibiting knee extension for 6 weeks, and this restriction of the movement led to the development of disuse atrophy, while the control group underwent no surgery. The operated and control groups were divided into subgroups according to PEMF application (1.5 mT for 45 days) or no PEMF. All groups were sacrificed after 6 weeks and had their entire rectus femoris removed. To measure the contraction force, the muscles were placed in an organ bath connected to a transducer. As a result of the atrophy, muscle mass and strength were reduced in the operated group, while no muscle mass loss was observed in the operated PEMF group. Furthermore, measurements of single, incomplete and full tetanic contraction force and contraction time (CT) did not change significantly in the operated group that received the PEMF application. The PEMF application prevented atrophy resulting from 6 weeks of immobility, according to the contraction parameters. The effects of PEMF on contraction force and CT provide a basis for further studies in which PEMF is investigated as a noninvasive therapy for disuse atrophy development. © 2022 Bioelectromagnetics Society.

C60 fullerene attenuates muscle force reduction in a rat during fatigue development

C60 fullerene (C60) as a nanocarbon particle, compatible with biological structures, capable of penetrating through cell membranes and effectively scavenging free radicals, is widely used in biomedicine. A protective effect of C60 on the biomechanics of fast (m. gastrocnemius) and slow (m. soleus) muscle contraction in rats and the pro- and antioxidant balance of muscle tissue during the development of muscle fatigue was studied compared to the same effect of the known antioxidant N-acetylcysteine (NAC). C60 and NAC were administered intraperitoneally at doses of 1 and 150 mg kg−1, respectively, daily for 5 days and 1 h before the start of the experiment. The following quantitative markers of muscle fatigue were used: the force of muscle contraction, the level of accumulation of secondary products of lipid peroxidation (TBARS) and the oxygen metabolite H2O2, the activity of first-line antioxidant defense enzymes (superoxide dismutase (SOD) and catalase (CAT)), and the condition of the glutathione system (reduced glutathione (GSH) content and the activity of the glutathione peroxidase (GPx) enzyme). The analysis of the muscle contraction force dynamics in rats against the background of induced muscle fatigue showed, that the effect of C60, 1 h after drug administration, was (15–17)% more effective on fast muscles than on slow muscles. A further slight increase in the effect of C60 was revealed after 2 h of drug injection, (7–9)% in the case of m. gastrocnemius and (5–6)% in the case of m. soleus. An increase in the effect of using C60 occurred within 4 days (the difference between 4 and 5 days did not exceed (3–5)%) and exceeded the effect of NAC by (32–34)%. The analysis of biochemical parameters in rat muscle tissues showed that long-term application of C60 contributed to their decrease by (10–30)% and (5–20)% in fast and slow muscles, respectively, on the 5th day of the experiment. At the same time, the protective effect of C60 was higher compared to NAC by (28–44)%. The obtained results indicate the prospect of using C60 as a potential protective nano agent to improve the efficiency of skeletal muscle function by modifying the reactive oxygen species-dependent mechanisms that play an important role in the processes of muscle fatigue development.

A Heart Failure Model Established by Pressure Overload Caused by Abdominal Aortic Contraction in Rat.

Heart failure is a complex clinical syndrome in which ventricular filling or ejection capacity is impaired due to structural or functional diseases of the heart. In order to establish a stable heart failure model, we investigated cardiac parameters in rats with abdominal aortic contraction and normal rats, including the left ventricular posterior wall diameter (LVPWd), the interventricular septum thickness of end-diastolic (IVSd), the left ventricular end-diastolic diameter (LVEDd), the left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS). Rats were randomly divided into experimental group (n = 20) and control group (n = 20). The experimental group underwent modified abdominal aortic constriction, while the control group only isolated the abdominal aorta without constriction. The results showed that the survival rate of rats in the experimental group was 85% after one week of operation, while the survival rate of rats in the control group was 100%. Five weeks after operation, the left ventricular posterior wall diameter (LVPWd) and the interventricular septum thickness of end-diastolic (IVSd) in the experimental group were all increased compared with those in the control group, and the differences were statistically significant (p < 0.05); the left ventricular end-diastolic diameter (LVEDd) in the experimental group showed an increasing trend compared with the control group, but p > 0.05; compared with the control group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the experimental group showed downward trend, but p > 0.05. 10 weeks after operation, the LVPWd, IVSd, and LVEDd of the experimental group were increased compared with the control group, p < 0.05, and the LVEF and LVFS of the experimental group were decreased compared with the control group, p < 0.05. Compared with the control group, the BNP of the experimental group increased significantly, p < 0.05. The heart weight index and left ventricular weight index of rats in the experimental group were significantly higher than those in the control group, p < 0.05. HE staining showed that the myocardial cells in the experimental group increased in volume, disordered cell arrangement, widened gaps, increased nuclear hyperchromia, and uneven staining. This paper provides a theoretical basis for the study of heart failure.

High Fat High Sucrose Diet Modifies Uterine Contractility and Cervical Resistance in Pregnant Rats: The Roles of Sex Hormones, Adipokines and Cytokines.

Background: In obesity, the adipose tissue becomes a very significant endocrine organ producing different factors called adipokines, such as leptin, adiponectin and kisspeptin; however, no data are available about their actions on uterine contraction in obese pregnant rats. Our aim was to study the impact of obesity on pregnant uterine contraction in a rat model. Methods: Obesity was induced by the consumption of a high fat high sucrose diet (HFHSD) for 9 weeks, including pregnancy. Glucose tolerance, sex hormone, cytokine and adipokine levels were measured. Uterine contractions and cervical resistance, as well as their responses to adipokines, were tested along with the expressions of their uterine receptors. Results: HFHSD increased body weight, and altered glucose tolerance and fat composition. The uterine leptin and kisspeptin pathway affect increased. The levels of proinflammatory cytokines were reduced, while the plasma level of progesterone was increased, resulting in weaker uterine contractions, and improving the uterine relaxing effects of adipokines. HFHSD reduced cervical resistance, but the core effect of adipokines is difficult to determine. Conclusions: Obesity in pregnant rats reduces uterine contractility and cytokine-induced inflammatory processes, and therefore obese pregnant rat methods are partially applicable for modelling human processes.

Relaxing Effects of Paracetamol on Uterine Spontaneous Contraction in Rats in Vitro

Aim: Paracetamol is a commonly used drug in acute and chronic pain. It is known that paracetamol, which is a pain reliever and antipyretic drug, is safe to use during pregnancy. The aim of this study was to investigate the effects of paracetamol on the uterine smooth muscle contraction- relaxation mechanism in female rats in diestrus.Material and Methods: Wistar-albino intact female rats were used in the study. Longitudinal strips of myometrium obtained from animals at the diestroeus stage. Stripes were suspended in an isolated organ bath containing crebs solution under 1 g passive tension. After the regulation period, paracetamol were added non-cumulatively at 1000μM and 2000μM concentrations. Before and after the application, the area under the curve (AUC) and peak to peak (p-p) values were normalized as % change.Results: Paracetamol caused a statistically significant decrease in p-p and area under the curve parameters of spontaneous uterine contractions at 1000 and 2000 μM doses (p &amp;lt;0.001).Conclusion: Paracetamol causes uterine relaxation by inhibiting uterine contraction. This effect should be taken into account in clinical use.

Antispasmodic Effect of Bergamot Essential Oil on Rat Isolated Gut Tissues.

Preclinical data indicate that bergamot essential oil (BEO) can modulate the synaptic functions within the central nervous system (CNS). Particularly, several data shows that essential oil is endowed with reproducible analgesic and anxiolytic effects that may derived from the ability to modulate the excitatory and inhibitory neurotransmission in the CNS. Although there are differences in the functional complexity of the enteric nervous system (ENS), it is likely that the phytocomplex has biological properties in gut superimposable to those showed in the CNS. Accordingly, the aim of this study was to investigate ex-vivo the effect of bergamot essential oil and its main constituents on the contractile activity of rat isolated colon, jejunum and ileum induced by different muscle stimulants such as acetylcholine (10−6 M) and potassium chloride (80 mM). Our present data demonstrate that BEO inhibits cholinergically- and non cholinergically-mediated contractions in rat isolated gut and that linalool is the most active component. These results suggest that the phytocomplex might be useful in the treatment of spastic disorders in ENS mainly characterized by the presence of pain; incidentally, irritable bowel syndrome (IBS) is a painful condition in which a role for neurotransmitter dysfunction has been envisaged. More investigation is required for clinical translation of the present data.

Repurposing of digoxin in pain and inflammation: An evidence-based study.

In recent years, the drug repositioning strategy has gained considerable attention in the drug discovery process that involves establishing new therapeutic uses of already known drugs. In line with this, we have identified digoxin a cardiac glycoside, as a potent inhibitor of soluble epoxide hydrolase (sEH) enzyme employing in silico high throughput screening protocols and further confirmed using in vitro cell-free sEH inhibitory assay and in vivo preclinical studies in rodents for its repurposing in hyperalgesia, inflammation, and related disorders. Oral administration of digoxin at dose 0.2 mg/kg significantly reduced (p < .0001) the allodynia in mice induced by using hot plate (3.6 ± 1.9) and tail-flick test (7.58 ± 0.9). In addition, digoxin at a dose of 0.2 mg/kg showed marked reduction (94%, p < .0001) in acetic acid-induced abdominal contraction in rats. Further, digoxin also demonstrated antipyretic activity (37.04 ± 0.2, p < .0001) and showed notable reduction (0.60 ± 0.06) in carrageenan-induced paw edema in rats. Also, the histopathological evaluation revealed that digoxin treatment attenuated the edema, neutrophil infiltration, and alveolar septal thickening in lung tissue. These findings are novel and highlight the newer insights towards repurposing digoxin as a new lead in the treatment of hyperalgesia, inflammation, and related disorders.

Effects of the healing activity of rosemary-of-Chapada (Lippia gracilis Schauer) on cutaneous lesions in rats.

ABSTRACTPurpose:To evaluate the effects of rosemary leaf essential oil-based ointments on the healing of rat skin lesions.Methods:Sixty adult male rats, with dorsal excisional skin wounds made surgically under anesthesia, were divided into three groups (n = 20): Sham group (untreated wounds); control group (CG, wounds treated with vehicle); and essential oil (EO) treated group (wounds treated with essential oil-based ointments), administered topically once daily. Skin wounds were evaluated at 4, 7, 14, and 21 days after EO or vehicle treatments. Lesions were analyzed macroscopically for the contraction degree. Formalin-fixed paraffin-embedded sections of skin wounds were used for histopathological evaluation.Results:Macroscopic evaluation showed wounds edges with thin crust without firmness and yellowish color, along with an improvement in wound contraction in EO group when compared to the other groups. A reduced inflammatory reaction, along with newly formed small diameter capillaries and more organized and elongated collagen fibers, were more frequently observed in EO group than in the other groups. Moreover, blood vessel number and collagen fibers density were significantly higher in EO group.Conclusions:Skin lesion treatment with rosemary leaf essential oil-based ointments accelerates the initial stages of healing, reduces inflammation, and increases angiogenesis, collagen fibers density, and wound contraction in rats.

Abstract 10234: Exaggerated Blood Pressure Response to Static Exercise Following Muscle Ischemia-Reperfusion: A Time-Course Investigation

Background: Peripheral artery disease (PAD) is one of the major cardiovascular concerns and dramatically reduces the blood flow supply in the affected limbs. A combination of revascularization surgery in the femoral artery and supervised exercise intervention is among the most general approaches for the treatment of PAD. However, the effects of ischemia-reperfusion (IR), which is one of the most predominant complications resulting from the revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. Methods: We examined the BP response to static muscle contraction in rats at different time points after the IR procedure. Four groups were included: 1. Sham rats; 2. Rats with 18 hours following IR (IR 18h); 3. Rats with 66 hours following IR (IR 66h); 4. Rats with 114 hours following IR (IR 114h). One-way ANOVA with LSD post-hoc test was applied to analyze the difference among groups. Data were presented as Mean ± Standard Deviation. Results: Compared with Sham group, the BP response to static muscle contraction was significantly increased in rats with all the investigated time points. The response of mean arterial pressure was 19±3 mmHg in Sham rats (n=6); 29±9 mmHg in IR 18h rats (n=8); 26±7 mmHg in IR 66h rats (n=10); 26±4 mmHg in IR 114h rats (n=9) ( P &lt;0.05; the groups at three time courses vs. Sham). There was no significant difference observed in the peak developed tension during muscle contraction among all the groups (Sham rats: 543±101g; IR 18h rats: 520±28g; IR 66h rats: 554±66g; IR 114h rats: 562±45g; P &gt;0.05). Conclusions: IR significantly exaggerates the static exercise-induced BP response. Whereas the BP response tends to decrease with the prolonged IR time, the exaggerated BP response remains through time points from post IR 18 hours to 114 hours. The data suggest that a chronic time course should be considered to alleviate IR-induced ischemic injury in PAD patients for clinical interventions appropriated and exercise.

Effects of dihydropyridine receptor signal on sarcoplasmic reticulum Ca2+ leakage after muscle contractions in rats

The purpose of this study is to investigate the mechanism underlying sarcoplasmic reticulum (SR) Ca2+ leakage at recovery phase after in vivo contractions. Rat gastrocnemius muscles were electrically stimulated in vivo, and then mechanically skinned fibers were prepared from the muscles excised 30 min after repeated high-intensity contractions. SR Ca2+ leakage was increased in the skinned fibers from stimulated muscles. Thereafter, SR Ca2+ leakage in skinned fibers was measured (1) under a continuously depolarized condition and (2) in the presence of nifedipine in the sealed transverse tubular system. In either of the two conditions, SR Ca2+ leakage in the rested fibers reached a level similar to that in the stimulated fibers. Furthermore, 1 mM tetracaine (Tet) treatment, but not 3 mM Mg2+ (3 Mg) treatment, lessened SR Ca2+ leakage in stimulated fibers. Depolarization-induced force in skinned fibers was more greatly decreased by Tet treatment than by 3 Mg treatment (92% reduction in Tet versus 31% reduction in 3 Mg), whereas caffeine-induced force in skinned fibers was similarly decreased by either treatment (73% reduction in Tet versus 75% reduction in 3 Mg). This difference indicates that Tet exerts a greater inhibitory effect on the dihydropyridine receptor (DHPR) signal to ryanodine receptor (RYR) than 3 Mg, although their inhibitory effects on RYR are almost similar. These results suggest that the increased Ca2+ leakage after muscle contractions is mainly caused by the orthograde signal of DHPRs to RYRs.

Role of Phospholipases A2 in Vascular Relaxation and Sympatholytic Effects of Five Australian Brown Snake, Pseudonaja spp., Venoms in Rat Isolated Tissues.

Human envenoming by Australian brown snakes (Pseudonaja spp.) may result in potentially life-threatening hypotension and subsequent cardiovascular collapse. There have been relatively few studies of the cardiovascular and sympathetic effects of Pseudonaja spp. venoms. In this study, we have examined the effects of venom from five brown snake species—P. affinis, aspidorhyncha, inframacula, nuchalis, and textilis—on cardiac inotropic and chronotropic responses, vascular tone, and sympathetic nerve-induced vascular contractions in rat isolated tissues. The role of phospholipases A2 (PLA2s) in venom-induced effects was assessed with the sPLA2 inhibitor varespladib. In rat isolated left and right atria, there were no physiologically relevant effects of Pseudonaja venoms (0.1–30 µg/ml) on left atrial force of contraction (inotropy) or right atrial rate (chronotropy). In contrast, in isolated small mesenteric arteries precontracted with a thromboxane mimetic, each of the five brown snake venoms (at 30 µg/ml) caused marked vasorelaxation (−60 to –90% of contractile tone). Pretreatment with varespladib (1 µM) significantly inhibited the vasorelaxation caused by P. aspidorhyncha, P. nuchalis, and P. textilis venoms. Electrically induced sympathetic nerve-mediated contractions of mesenteric arteries were significantly attenuated by only P. textilis, and P. affinis venoms (30 µg/ml) and these sympatholytic effects were inhibited by varespladib (1 µM). Based on their inhibition with the sPLA2 inhibitor varespladib, we conclude that PLA2 toxins in P. aspidorhyncha, P. nuchalis, and P. textilis venoms are involved in brown snake venom-induced vasorelaxation and the sympatholytic effects of P. affinis, and P. textilis venoms. Our study supports the promising potential role of varespladib as an initial (pre-referral) and/or adjunct (in combination with antivenom) therapeutic agent for brown snake envenoming.