Rat Blood Samples Research Articles

The dynamic distribution patterns and lung targeting efficiency in rats of 9 bioactive components in Siraitia grosvenorii.

Siraitia grosvenorii (S. grosvenorii) is a traditional herbal medicine employed for the prevention of lung diseases. Mogrosides and flavonoids are postulated to be the principal active components. Nevertheless, the dynamic distribution of its active components in vivo and the amount of accumulation in the lung target tissue remain indistinct. This study investigates the dynamic distribution patterns of 9 bioactive components within the extract of S. grosvenorii in rat blood, heart, liver, spleen, lung, and kidney, along with its pulmonary targeting. The blood, heart, liver, spleen, lung, and kidney samples of rats were obtained at diverse time points after oral administration of S. grosvenorii decotion, and a UPLC-MS/MS method was developed to determine the contents of 9 bioactive components (Siamenoside I, Grosvenorine, 11-O-Mogroside V, Mogroside II-E, Mogroside III-E, Mogroside IV-A, Mogroside V, Mogroside VI and Kaempferitrin) within the samples. The concentration-time curves of each component in each sample were plotted and the pharmacokinetic parameters were computed. The AUC0→∞ and Cmax of 9 bioactive components in lung tissue were conspicuously higher than those in heart, liver, spleen, and kidney. For instance, the AUC0→∞ of Mogroside V in lung tissue was 7.20-55.54 times higher than that in blood and other tissues, and the Cmax in lung tissue was 3.315-96.70 times higher than that in blood and other tissues. The lung target efficiency of 9 bioactive components ranged from 1.885 to 15.80, indicating that the active components of S. grosvenorii exerting pharmacological effects are highly concentrated in the lung target tissue. The Tmax of 9 bioactive components in blood was within the range of 10.20-100.2min, while the Tmax of the heart and liver was 20min. The Tmax of all the components in the lung was 50min, while the Tmax of the spleen and kidney was from 80 to 100min, suggesting that 9 bioactive components entered the blood rapidly and then distributed to the heart and liver in large quantities, before entering the lung tissue in large quantities and eventually distributing to the spleen and kidney. The elimination half-life (T1/2) of the majority of 9 bioactive components was less than 1h, and the MRT of most of them was less than 3h. S. grosvenorii is a naturally lung-targeted herbal medicine, and the clinical administration ought to be based on pharmacokinetic parameters such as Tmax, Cmax, AUC0→∞, T1/2, and MET0→∞ in lung tissue for designing a precise, rigorous, and rational administration plan.

Fabrication of a cell irradiation technique by alpha-particles using allyl diglycol carbonate (ADC) detector and micro-capillary tubes.

To study the impact of micro-alpha irradiation collimator with a specific design to irradiate specific normal or up-normal cells using capillary tubes and nuclear track detector type CR-39. The in vitro experimental study was conducted at radiobiology Lab, of the Physics department, Salahaddin University, Erbil, Iraq from February to April 2022. Several alpha irradiation collimators were calibrated using allyl diglycol carbonate to fabricate a suitable blood cell irradiation technique. Time of irradiation and alpha particle energy were calibrated. Healthy blood samples of Albino rats and cancer blood samples were used to assess the applicability of the fabricated cell irradiation technique. The Rats were divided into intervention and control groups. Data was analysed using SPSS software version 28. Of the 15 healthy, male Albino rats having a mean weight of 230±12g each, there were 12(80%) in the intervention group and 3(20%) in the control group. Microcapillary tubes with suitable diameters had high stability for deposition of a sufficient density of alpha particles on the surface of allyl diglycol carbonate and blood samples. The optimum time of irradiation that had a significant (p<0.05) effect was 20 sec corresponding to alpha energy 4.5MeV. Low irradiation time had significant impact of alpha particles on the average percentage of lymphocyte and neutrophil cells.

Protective effects of lupeol in rats with renal ischemia‑reperfusion injury.

Acute kidney injury (AKI) caused by ischemia and, exogenous or endogenous nephrotoxic agents poses a serious health issue. AKI is seen in 1% of all hospital admissions, 2-5% of hospitalizations and 67% of intensive care unit (ICU) patients. The in-hospital mortality rates for AKI is 40-50, and >50% for ICU patients. Ischemia-reperfusion (I/R) injury in the kidney can activate inflammatory responses and oxidative stress, resulting in AKI. The common endpoint in acute tubular necrosis is a cellular insult secondary to ischemia or direct toxins, which results in effacement of brush border, cell death and decreased function of tubular cells. The aim of the present study was to assess if the reported antioxidant and anti-inflammatory agent lupeol can exert any effects against renal I/R damage. In total, 24 Wistar Albino rats were randomly assigned into four groups of 6, namely Sham, lupeol, ischemia and therapy groups. In the lupeol group, intraperitoneal administration of 100 mg/kg lupeol was given 1 h before laparotomy, whilst only laparotomy was conducted in the sham group. The renal arteries of both kidneys were clamped for 45 min, 1 h after either intraperitoneal saline injection (in the ischemia group) or 100 mg/kg lupeol application (in the therapy group). The blood samples and renal tissues of all rats were collected after 24 h. In blood samples, blood urea nitrogen (BUN) was measured by the urease enzymatic method, and creatinine was measured by the kinetic Jaffe method. Using ELISA method, TNF-α and IL-6 levels were measured in the blood samples, whereas malondialdehyde (MDA), glutathione (GSH), caspase-3 levels were measured in kidney tissues. In addition, kidney histopathological analysis was performed by evaluating the degree of degeneration, tubular dilatation, interstitial lymphocyte infiltration, protein cylinders, necrosis and loss of brush borders. It was determined that renal damage occurred due to higher BUN, creatinine, MDA, TNF-α and caspase-3 values observed in the kidney tissues and blood samples of rats in ischemia group compared with the Sham group. Compared with those in the ischemia group, rats in the therapy group exhibited increased levels of GSH and reduced levels of BUN, TNF-α, MDA. Furthermore, the ischemia group also had reduced histopathological damage scores. Although differences in creatinine, IL-6 and caspase-3 levels were not statistically significant, they were markedly reduced in the treatment group. Taken together, these findings suggest that lupeol can prevent kidney damage as mainly evidenced by the reduced histopathological damage scores, decreased levels of oxidative stress and reduced levels of inflammatory markers. These properties may allow lupeol to be used in the treatment of AKI.

Antitumor, antioxidant, and anti-inflammatory activity of spirulina against 7,12-dimethylbenzanthracene-induced mammary cancer

Background Breast cancer is the most abundant malignancies worldwide; however, its current therapies encounter drug resistance or exhibit numerous side effects. Marine and freshwater algal biomasses, such as spirulina, are rich with many biological active components. Objective The main objective of the current study was to investigate the therapeutic, antioxidant, and immune-modulating efficiency of spirulina on breast tumor modelled female rats, especially through the inhibition of the phosphoinositide 3-kinases/Akt/mammalian target of rapamycin pathway. Materials and methods 7,12-dimethylbenzanthracene (DMBA)-induced mammary cancer rats were ingested with spirulina (500 mg/kg/day) for 6 weeks, then blood and tissue samples of normal and spirulina-treated cancer rats were obtained and tested for biochemical, immunological, and histopathological assessments. Cancer model is used in this experiment. Results The results showed that spirulina is rich in phenolic compounds that have high scavenger activity and reducing power reflecting the antioxidant potential of spirulina. Treatment of DMBA-induced mammary cancer rats with spirulina resulted in improvement in mammary oxidative stress status that was distorted due to DMBA administration; meanwhile, superoxide dismutase, glutathione peroxidase, and reduced glutathione values were elevated significantly coupled with a marked drop in nitric oxide and malondialdehyde levels. In addition, spirulina boosts the immune-modulating response against tumor as the serum proinflammatory cytokines (tumor necrosis factor alpha, interlukin-1 beta, and interlukin-6) were markedly downregulated, and associated with inhibition of Akt and mammalian target of rapamycin pathway; this in turn suppress the tumor proliferation and progression. Furthermore, the prognosis of the treatment was indicated by the clear reduction of serum cancer antigen 15.3 level accompanied by elevation in serum level of the apoptotic biomarkers (caspase-3 and CD4) inferring the upregulation of tumor suppressor genes. Similarly, spirulina ameliorated lipid profile and the biochemical markers of hepatorenal functions (alanine transaminase, aspartate transaminase, urea, and creatinine) that were disturbed by DMBA; therefore, it has a positive impact on the body health. These biochemical improvements were associated with a notable improvement in the histological architecture of the mammary tissue. Conclusion In conclusion, spirulina has proved considerable antitumor, antioxidant, and anti-inflammatory activities against DMBA-induced mammary cancer.

Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in blood samples of rats using GC-MS/MS

Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in blood samples of rats using GC-MS/MS

Potensi Mieloprotektif Kombinasi Curcuma xanthorriza, Curcuma domestica, dan Zingiber officinale terhadap Perubahan Biokimia pada Tikus yang Diinduksi Doksorubisin

Doxorubicin as an anticancer drug has myelosuppressive side effects. This study aimed to investigate the possibility of myeloprotective role of the natural antioxidant Curcuma xanthorrhiza, Zingiber officinale, and Curcuma domestica in rats induced by doxorubicin. Wistar male rats were divided into four groups and treated with (1) 0.9% NaCl as a control group, (2) doxorubicin 5 mg/kg intraperitoneally, 4 times in 14 days (days 1, 5, 9, 13); (3) doxorubicin + extract 250 mg/kg/day orally for 14 days; (4) doxorubicin + extract of 500 mg/kg/day orally for 14 days. Blood samples of rats were taken on day 15th and sacrificed for harvesting spleen organ. White blood cells were counted, and spleen weights were evaluated as markers of myelosuppressive effect. The amount of white blood cells and spleen weights were reduced in the doxorubicin treated groups. Whereas in the group treated by the extract (250 mg and 500 mg) + doxorubicin, the amount of white blood cells and spleen weights were increased. These results indicated that the extract combination of Curcuma xanthorrhiza, Zingiber officinale, and Curcuma domestica has myeloprotective activity by keeping the amount of white blood cells and spleen weights.

Effects of boric acid on oxidant-antioxidant, proinflammatory cytokine levels, and biochemical parameters in aged rats

Purpose: As a result of the literature studies, it was seen that boric acid was the subject of many studies, and its effects on living things were investigated and examined. The aim of this study was to investigate the effects of oral boric acid supplementation at pharmacologic doses on physiological and biochemical systems in aged rats.&#x0D; Material and methods: A total of 32 Wistar Albino male-aged rats were randomly and equally divided into the following four groups: 1st; Control=1 ml saline; 2nd; Low-dose boric acid (L-BA)=10 mg/kg; 3rd; Medium-dose boric acid (M-BA)=20 mg/kg; 4th; High-dose boric acid (H-BA)=40 mg/kg. Boric acid was given orally to aged rats for 28 days. Blood, liver, and kidney samples of rats were collected on day 29 to be analyzed for oxidants, antioxidants, proinflammatory cytokines, and biochemical changes.&#x0D; Result: Boric acid significantly increased albumin, total protein, calcium levels equally in all boric acid groups compared to the control group (p

The therapeutic effect of alcoholic extract of Fumaria parviflora on high-fat diet-induced nonalcoholic fatty liver in rats: an animal experiment.

Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are exploring other options. This study focused on the effects of Fumaria parviflora (FP) extracts on NAFLD induced by a high-fat diet in rats. Thirty-five 10-week-old male Wister-Albino rats were divided into seven groups: normal diet control, high fat diet control, high fat diet with oral normal saline gavage, high fat diet with oral Atorvastatin gavage, and three groups receiving high fat diet with FP extract in 200mg/kg, 400mg/kg, and 700mg/kg.Blood samples of rats were used for the measurement of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP).1×1cm Liver biopsies were taken, stained with Trichrome Stain (Masson) and Hematoxylin and eosin (H&E) stain for evaluation by a pathologist. Lab results showed that FP extract inhibits weight gain, has positive effects on triglyceride and alkaline phosphatase levels, and reduces hepatocyte ballooning and inflammation in rats. FP extract may lower liver enzymes and have a positive impact on triglyceride, LDL, and HDL levels in rats with NAFLD.

Development and validation of cardiac diffusion weighted magnetic resonance imaging for the diagnosis of myocardial injury in small animal models

Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10–3 mm2/s vs. 1.578 ± 0.144 * 10–3 mm2/s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury (P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.

"In Vitro Evaluation of the Antiplatelet Activity of Paravat Shakrita"

Platelet aggregation, a crucial process in thrombotic disorders, underscores the necessity for effective preventive and therapeutic measures. This study compares the antiplatelet effects of Aspirin, a well-established drug, with Paravat Shakrita, a lesser-known formulation from Ayurvedic texts. It underwent GCMS and microbiological analysis to determine its chemical composition and microbial load. Using an in vitro model with rat blood samples, we conducted a Platelet Aggregation Inhibition Assay. As expected, Aspirin inhibited platelet aggregation in a concentration-dependent manner, consistent with its known mechanism. Despite limited documentation, Paravat Shakrita exhibited potent antiplatelet properties, also showing dose-dependent effects. Interestingly, Paravat Shakrita demonstrated comparable or even superior effects at higher concentrations compared to Aspirin. The IC50 values revealed similar inhibitory potency between Paravat Shakrita and Aspirin. This comparison unveiled distinct mechanisms of action, providing various therapeutic options against platelet-mediated thrombosis. While promising, further investigation is crucial to understand Paravat Shakrita's mechanism, ensure its safety, and determine its clinical significance.

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 μg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 μg/kg·bw and 0.11 μmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

Donepezil and Quercetin Simultaneous Estimation in Rat Plasma Using Developed Bioanalytical HPLC Method: Relevance in Pharmacokinetic Studies

The objective of this investigation was to create and apply a reliable reverse phase high performance liquid chromatography (RP-HPLC) technique for the concurrent measurement of donepezil (DPZ) and quercetin (QT) in rat blood samples for pharmacokinetic research. This is the first publication that introduces a method for DPZ and QT simultaneous determination in rat plasma by high-performance liquid chromatography (HPLC). Using a mobile phase of methanol and HPLC grade water (pH 2.8; adjusted with 0.05% v/v orthophosphoric acid) 45:55 v/v with 2-3 drops of triethylamine (TEA) in an isocratic elution mode at flow rate of 1.0ml/min, DPZ and QT were successfully separated chromatographically on a Hypersil gold C-18 column (250 mm × 4.6 mm, 5μm). The retention time for DPZ and QT was observed to be 6.3 and 12.3 minutes and was detected at an isobestic wavelength of 273 nm using a UV detector. The method was shown to be precise (%RSD &lt; 2%), accurate (96–100%), and specific for the simultaneous detection of DPZ and QT. Several freeze-thaw cycles of the treated plasma samples did not significantly affect the analyte’s stability. The method’s applicability was subsequently confirmed through an oral pharmacokinetic investigation in rats. Since the results were deemed trustworthy, the validated RP-HPLC method may be used to simultaneously detect and quantify both drugs. The method worked well for evaluating the pharmacokinetic characteristics in wistar rats following a single oral dose of 5 mg/kg of QT and 10 mg/kg of DPZ. It is well acknowledged that the chromatographic process is straightforward, robust, accurate, exact, and repeatable.

Providing Of Mahkota Dewa Fruit Extract (Phaleria Macrocarpa) To Reduce Malondialdehyde Levels In The Blood Of White Rats (Rattus Norvegicus) Triggered By Excessive Physical Activity

Anti-inflammatory, antioxidant, and apoptosis-modulating potential are just a few biological activities that have garnered much interest in natural food-derived components during the past two decades. Mahkota Dewa fruit (Phaleria macrocarpa) has several beneficial pharmacological activities. This study investigated whether Mahkota Dewa fruit extract (Phaleria macrocarpa) reduced malondialdehyde levels in blood samples of white rats (Rattus norvegicus) generated by excessive physical activity. The samples for this study were white rats (Rattus norvegicus) weighing 160-200 gr and 2-3 months old. The independent variable was the Mahkota Dewa fruit extract (Phaleria macrocarpa). The dependent variable was excessive physical activity-induced malondialdehyde levels in white rats (Rattus norvegicus). The average Malondialdehyde (MDA) levels show that the group given 5 ml of the Mahkota Dewa fruit extract (Phaleria macrocarpa) had tremendous success in lowering MDA levels compared to the other groups. The results of the observations and data analysis show that administration of the extract can reduce MDA levels significantly in male Wistar rats (Rattus norvegicus) because of too much exercise.

Spexin may induce mitochondrial biogenesis in white and brown adipocytes via the hypothalamus-pituitary-thyroid (HPT) axis

AimThe present study aimed to investigate the effect of the intracerebroventricular (icv) administration of spexin on the hypothalamus-pituitary-thyroid (HPT) axis (TRH, TSH, T4 and T3 hormones) and energy expenditure (PGC-1α and UCP1 genes) in white adipose (WAT) and brown adipose tissues (BAT) in rats. Furthermore, the study aimed to determine the effects of spexin on food-water consumption and body weight of rats. Material and methodThe study was conducted with 40 male rats that were divided into 4 groups: Control, Sham, Spexin 30 and Spexin 100 (n = 10). Spexin (1 μl/hour) was administered to rats other than those in the control group for 7 days with osmotic minipumps intracerebroventricularly, artificial cerebrospinal fluid (vehicle) was administered to the Sham group, and 30 nMol and 100 nMol spexin was infused to the Spexin 30 and Spexin 100 groups, respectively. Food-water consumption and body weight of the rats were monitored during the experiments. After the seven-day infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined with ELISA on rat blood samples. Also, TRH gene expression levels from the hypothalamus tissues and PGC-1α and UCP1 expression levels from WAT and BAT were determined by real-time PCR. FindingsIt was determined that icv spexin infusion reduced daily food consumption and body weight without leading to a significant change in water consumption (p < 0.05). Icv spexin infusion significantly decreased serum TSH, and increased fT4 and fT3 levels when compared to control and sham groups (p < 0.05). Moreover, icv spexin infusion increased the TRH expressions in the hypothalamus tissues and PGC-1α UCP1 in the WAT and BAT (p < 0.05). ConclusionIcv Spexin infusion may have effects on food consumption and body weight as well as, thyroid hormones and energy metabolism.

Subclavian Vein Blood Sampling in Conscious Rats.

There are several established methods for obtaining repeated blood samples from rats, with the most commonly employed methods being lateral tail vein sampling without anesthesia and jugular vein sampling with anesthesia. However, most of these methods require assistance and anesthetic equipment and sometimes pose difficulties in terms of blood collection or the poor quality of blood samples. In addition, these methods of blood collection consume significant time and human resources when repeated blood sampling is required for a large number of rats. This study presents a technique for repetitive blood sampling in non-anesthetized rats by a single proficient individual. Highly satisfactory blood samples can be obtained by puncturing the subclavian vein. The method demonstrated an impressive overall success rate of 95%, with a median time of merely 2 min from rat restraint to the completion of blood collection. Furthermore, performing consecutive blood collections within the designated range does not inflict any harm on the rats. This method is worth promoting for blood collection, especially in large-scale pharmacokinetic studies.

The effects of the differentiated macrophages by dexamethasone on the immune responses

The characteristics of M2 macrophages suggest immunotherapeutic approaches for inducing immunological tolerance. The current study aimed to evaluate the effect of Dexamethasone (Dex) treatment on monocytes polarization and its impact on immune responses. The monocytes were extracted from the rat's blood samples. The effects of Dex concentration and treatment duration on monocyte viability, phagocytosis of rabbit red blood cell (RRBC) antigens, and cytokine gene expression were evaluated using MTT, ELISA, and Real-Time PCR analysis, respectively. The monocytes treated with Dex were injected into the rats as an autograft. The effects of the grafted cells were assessed on immune responses, monocyte differentiation, and pathological lesions, in comparison to the control groups.Treatment of monocytes with 10-5 M of Dex for 48 h increased the expression of IL-10 and TGF-β genes, while reducing the expression of TNF-α and IL-1 genes. The monocytes treated with antigen and Dex showed higher CD206 gene expression compared to CD80. The cells that were treated with Dex had the highest concentration of antigens after five days. Administration of the grafted cells to the animals has some significant effects on innate immune responses and no impact on pathological lesions. The group that received cells treated with Dex and antigen experienced a significant decrease in anti-RBC antibody titers. Additionally, there was a significant difference in the expression of cytokine genes and M2 differentiation markers among the groups that were evaluated. The effects of Dex on the viability and differentiation of monocytes depend on the dosage, timing, and duration of the treatment.

EXPERIMENTAL STUDY OF ERYTHROCYTE ENERGY METABOLISM UNDER INHALATIONS OF NITRIC OXIDE

Abstract Biological effects of nitric oxide are multiply, including vasoactive activity, participation in neurotransmission and intercellular communication etc. These effects are associated with endogenous releasing of nitric oxide, but influence of exogenous administration of this substance does not study in details. In particular, systemic action of nitric oxide inhalations is not so clear. The aim of this work was the investigation of nitric oxide inhalations action on some parameters of energy and oxidative metabolism of healthy rat blood. Wistar rats were randomly divided into two groups: control group (without any manipulations; n=10) and main group (n=10) with inhalations by nitric oxide-containing gas flow (20 ppm). Lactate dehydrogenase and lactate level were estimated in rat blood samples. In addition, we calculated a number of integral coefficients of energy metabolism, such as substrate provision coefficient and coefficient of energy reactions balance. Our experiments demonstrate that 10-days course of inhalations of low nitric oxide doses (20 ppm) increases the adaptive potential of healthy rats’ organism. One of these positive effects is associated with activation of some components of energy metabolism. First of all, it realized through stimulation of catalytic activity of lactate dehydrogenase, including its erythrocyte pool. Observed metabolic effect provides the basis for pathogenic correction of diseases, associated with hypoxia, oxidative stress and energy deficiency.

The aqueous extract of Leptadenia Pyrotechnica Decne enhances the innate immune response and inhibits the acquired immune response, while the aqueous extract of Capparis Cartilaginea Decne does the exact opposite in Healthy Rats

Leptadenia pyrotechnica (Forssk.) Decne. (LP) and Capparis cartilaginea Decne. (CC) are plants used in local folk medicine, although there are no published studies on their physiological, hematological, and immune system effects. This study is the first to determine and compare the effects of aqueous LP and CC extracts on body weight parameters, consumptions of feed and water, and the differential complete blood counts in blood samples of healthy Wister albino rats. Six groups of rats (3 rats/group) were orally gavage separately with the aqueous extracts of LP (groups LP1, LP2, and LP3, respectively) and CC (groups CC1, CC2, and CC3, respectively) at concentrations of 30, 100, and 200 mg/kg body weight, while three control rats were gavage with water, daily for two weeks. Body weights were measured daily. The mean total body weights were not significantly different between all groups, between the experimental groups and the control group, and between the equal concentrations of LP and CC groups. The mean total and daily body weight gains and percent relative total body weight gain for the LP3 group were significantly lower compared with the control group. The mean feed and water intakes were highly significantly lower for the LP2, LP3, CC2, and CC3 groups compared with the control group, and for the LP3 group it was significantly lower compared with the CC3 group. The FER for the LP3 group was significantly lower compared with the control group. The mean lymphocyte percent for CC1 was significantly higher and the mean lymphocyte count for LP1 was significantly lower compared with the control. The mean neutrophil percent for LP1 was significantly higher than for CC1 and the mean lymphocyte percents for LP1 and LP2 were significantly lower than for CC1 and CC2. In conclusion, the LP extract enhances the innate immune response and inhibits the acquired immune response, while the CC extract does the exact opposite. Thus, the extract may be used for modulating the immune response.

METTL3-mediated ANXA2 inhibition confers neuroprotection in ischemic stroke: Evidence from in vivo and in vitro studies.

Given the important role of m6A, the most common and reversible mRNA modification, in the pathogenesis of ischemic stroke, this study investigates the mechanisms of m6A methyltransferase METTL3 in neuronal damage in ischemic stroke. In silico analysis was used to pinpoint the expression of ANXA2, which was verified in clinical peripheral blood samples. SD rats were used for middle cerebral artery occlusion (MCAO) establishment. The experimental data suggested that T lymphocytes were increased in peripheral blood samples of ischemic stroke patients and MCAO rats. The MCAO rats were treated with anti-ANXA2 alone or combined with RP101075 (T lymphocyte infiltration inhibitor), followed by brain injury assessment. Oxygen-glucose deprivation/reoxygenation (OGD/R) was induced in primary cortical neurons, where shRNAs targeting ANXA2 or METTL3, or overexpression plasmids of METTL3 were introduced to verify the regulatory function for METTL3. Inhibition of T lymphocyte migration to the ischemic brain reduced brain injury in MCAO rats and neuronal damage in OGD/R-exposed neurons. Ablation of ANXA2 in T lymphocytes inhibited the migration of T lymphocytes to the ischemic brain and reduced neuronal damage. Mechanistically, METTL3 reduced ANXA2 expression in T lymphocytes through m6A modification and inhibited p38MAPK/MMP-9 pathway activation, exerting protective effects against neuronal damage in ischemic stroke. Overall, this study reveals the neuroprotective effects of METTL3-mediated ANXA2/p38MAPK/MMP-9 inhibition against ischemic stroke.

Effect of eel and tempe composite flour supplementation on the nutritional status biomarkers of rats with a restricted protein diet: Data from a preclinical trial

Incorporating eels and tempe can replace and complement the content of proteins, macronutrients, and micronutrients, which may be related to curative effects for malnutrition. In addition, converting the ingredients into a form of flour can increase their shelf life and nutrient concentration. Therefore, an in vivo approach was undertaken to explore further the nutritional status value of biomarkers in malnourished male rats (Rattus norvegicus) after Eel and Tempe Composite (ETC) flour supplementation. Data was collected from blood samples (both plasma and serum) of rats in all groups, and the appropriate biomarkers were analyzed. The final data presented in this study is openly available and can be further analyzed using statistical means to determine the dose of ETC flour as the basis of clinical trials, which other researchers can reproduce. This data may also be valuable for those interested in using different analytical methods to research the same questions or even new preclinical studies focusing solely on nutritional status biomarker analysis methods, including clinical trial prospects.