Rat Blood Research Articles

AUT-M enterosorbent stabilizes glutathione system in vincristine-treated rats with dimethylhydrazine-induced colon cancer

Colorectal cancer is one of the leading causes of mortality in the world. The search for new methods of therapy for this disease that could correct the state of oxidative stress during the development of neoplasms is up to date. The aim of this work was to study the level of reduced glutathione and the activity of glutathione-dependent enzymes in the development of 1,2 dimethylhydrazine-induced colon cancer in rats while treated with vincristine and the use of enterosorbent. To induce carcinogenesis, dimethylhydrazine was administered to male rats subcutaneously for 30 weeks at a dose of 7.2 mg/kg of body weight. The rats with induced colon cancer received entorosorbent per os at a dose of 0.2 g per 100 g of body weight daily for 21 days. After detoxification therapy, the rats were administered cytostatic vincristine daily at a dose of 0.23 mg/kg for 14 days. A decrease in the content of reduced glutathione, the activity of glutathione reductase and glutathione peroxidase in the blood and liver tissue of rats with colorectal cancer was established. The use of enterosorbent­ AUT-M was shown to be effective in stabilizing the indicators of the glutathione system in rats with induced colon cancer. Cytostatic vincristine did not significantly affect the change of the studied indicators, confirming the effectiveness of previous sorption measures. Keywords: blood, colorectal cancer, entorosorbent, glutathione, glutathione peroxidase, glutathione reductase, liver, vincristine

Obesity as a Limiting Factor for Remote Ischemic Postconditioning-Mediated Neuroprotection after Stroke.

Remote ischemic postconditioning (RIPostC) may protect the brain from ischemia/reperfusion (I/R) injury. The association between RIPostC and obesity has not yet been extensively studied. Twelve-week-old male Zucker diabetic fatty (ZDF; n=68) and Zucker diabetic lean (ZDL; n=51) rats were subjected to focal cerebral ischemia for 90 minutes, followed by 24 hours of reperfusion. RIPostC was performed with 5-minute I/R cycles using a tourniquet on the right hind limb. The results showed a negative association between obesity and neurological impairment in ischemic animals. We observed a 70% greater infarct size in ZDF rats compared with their lean counterparts, as evaluated by 2,3,5-triphenyltetrazolium chloride staining. To measure the total fragmented DNA in peripheral lymphocytes, comet assay was performed. Obese rats exhibited higher levels of DNA damage (by approximately 135%) in peripheral blood lymphocytes even before the induction of stroke. RIPostC did not attenuate oxidative stress in the blood in obese rats subjected to ischemia. Focal cerebral ischemia increased core and penumbra tissue glutamate release in the brain and decreased it in the blood of ischemic ZDL rats, and these changes improved following RIPostC treatment. However, changes in blood and tissue glutamate content were not detected in ischemic ZDF rats or after RIPostC intervention. Our findings suggest that obese animals respond more severely to ischemia-reperfusion brain injury. However, obese animals did not achieve neuroprotective benefits of RIPostC treatment.

Biochemical Profile of White Rat Blood during Mating and Pregnancy Treated with Steeping Water of Dried Gedi Leaves (Abelmoschus manihot)

Biochemical Profile of White Rat Blood during Mating and Pregnancy Treated with Steeping Water of Dried Gedi Leaves (Abelmoschus manihot)

Effect of Formaldehyde Inhalation on Leukocyte Counts and Malondialdehyde Levels in Wistar Rats (Rattus norvegicus)

Formaldehyde is a chemical compound that is often found in everyday life, such as in the chemical industry to research laboratories. Formaldehyde has toxic properties that can harm humans in long term exposure. The genotoxic and cytotoxic properties of formaldehyde can cause oxidative stress. This study assesses the number of leukocytes and levels of malondialdehyde in Wistar rats induced by 40 ppm formaldehyde. This study used 12 Wistar rats taken at random and put into 2 groups, namely the control and treatment groups. The treatment group was given formaldehyde inhalation at a concentration of 40 ppm for 16 weeks. At the 16th week, rat blood was taken retroorbital to calculate the number of leukocytes and levels of malondialdehyde. The calculation results were then tested statistically using IBM SPSS Statistics 25 software. The results showed that there was no significant difference (p>0.05) between the number of leukocytes in the control group and the treatment group. This study also showed that there was a significant difference (p<0.05) between malondialdehyde levels in the control group and the treatment group. In conclusion, there was no effect of formaldehyde induction with a concentration of 40 ppm on the number of leukocytes and there was an effect of formaldehyde induction with a concentration of 40 ppm on malondialdehyde levels in Wistar rats.

Anti-cancer and neuroprotective effects of conjugated graphene quantum dot in brain tumor-bearing rat model

Glioblastoma has been recognized as a most complex and highly malignant type of primary brain tumor. The rapid progression brain tumor model was developed by direct intracranial administration of ENU at the different focal brain points in the rat brains. The GQD was synthesized by bottom-up technique and functionalized with Trastuzumab and Caspase-8 antibody by Carbodiimide-amidation activation. The in-vitro cytotoxicity MTT assay was performed with all the GQD conjugates in SK-N-SH and N2a cell lines. The acute and chronic toxicity of synthesized GQD was performed in healthy rats and evaluated the hemolytic activity and CRP levels. A synthesized quasi-spherical 2D tiny GQD has a particle size of less than 10 nm and a 12.7% quantum yield. DSL, TEM, AFM, FTIR, and fluorescence spectroscopy characterized the GQD conjugates. In-silico molecular docking was a conformed static interaction between GQD and antibodies. GQD-conjugates showed dose-dependent toxicity in both cell lines and mild acute toxicity in rat blood. The GBM tumor-bearing rats were assessed for the anticancer and neuroprotective activity of the GQD conjugates. Histopathology, immunohistochemistry, metabolic, and inflammatory tumor biomarker estimation showed that the GQD_Caspase-8 conjugate showed better anti-tumor and neuroprotective effects than other conjugates.

Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse

Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 μM (A23187). The total protein and TGF-β1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Diabetes-correcting and antioxidant effects of grape pomace extract rich in natural complex of polyphenols

Background. The positive health effects of polyphenols have led to an increased scientific interest in these natural compounds over the past decade. Many studies confirm the effectiveness of polyphenols as additional therapy in diabetes, especially due to the sugar-lowering effect of polyphenols. The aim of the research was to investigate the morphological and functional state of peripheral blood erythrocytes and the indices of oxidative stress in the liver of rats with experimental diabetes and after the administration of grape pomace extract rich in natural complex of polyphenols. Materials and Methods. We obtained grape pomace extract, which contains a variety of polyphenolic compounds. Rats of the following groups were used in the experiments: control animals, animals treated with grape pomace extract rich in natural complex of polyphenols for 14 days, animals with streptozotocin-induced diabetes mellitus, and animals with streptozotocin-induced diabetes mellitus treated with grape pomace extract rich in natural complex of polyphenols for 14 days. The number of erythrocytes and reticulocytes, the concentration of hemoglobin and glycated hemoglobin were determined in the peripheral blood of rats. The activities of catalase, superoxide dismutase and the content of thiobarbituric acid-reactive substance and carbonyl groups of proteins were determined in the liver tissues of rats. Results. The study has shown an increase in the number of erythrocytes and the level of hemoglobin, a decrease in the level of glycated hemoglobin and the number of reticulocytes in the peripheral blood of rats after administration of grape pomace extract rich in natural complex of polyphenols to rats with experimental diabetes. A decrease in the content of thiobarbituric acid-reactive substance and the content of carbonyl groups of proteins of neutral and basic character and an increase in the activity of catalase and superoxide dismutase in liver tissues were found under the same conditions. Conclusions. The results indicate that the extract of the natural complex of polyphenols is capable of correcting the morphological and functional state of erythrocytes, as well as improving the activity of antioxidant enzymes and the content of marker molecules of oxidative stress in hepatocytes of rats under experimental diabetes mellitus.

Aurantio-obtusin alleviates allergic responses in ovalbumin-induced rhinitis

Allergic rhinitis (AR) is a growing global health concern. Despite being non-fatal, it has a detrimental effect on people's quality of life and poses a significant economic burden. In this study, we aimed to evaluate the anti-allergic effects of aurantio-obtusin against ovalbumin-induced murine model of allergic rhinitis. Aurantio-obtusin was administered to rats orally after sensitization to ovalbumin. Results of the study suggested that aurantio-obtusin causes a significant reduction in nose rubs and sneeze as compared to the vehicle-treated disease control group. The aurantio-obtusin treated group showed a dose-dependent significant reduction in serum TNF-α, IL-4, and IL-6 levels as well as histamine levels in the nasal mucosa. Additionally, it decreased neutrophil and eosinophil numbers in blood of AR rats'. In the nasal tissues of the vehicle-treated rats that were subjected to an OVA challenge, the histology of the nasal mucosa of AR rats revealed aberrant histological changes. A variety of histological abnormalities, including vascular congestion in the nasal mucosa, substantial inflammatory cell infiltration, and obvious alveolar wall oedema were present. In the rats treated with aurantio-obtusin, these characteristics were reversed. Collectively, the findings suggests that aurantio-obtusin could be used to enhance current AR treatment approaches.

In Situ Growth of Functional Hydrogel Coatings by a Reactive Polyurethane for Biomedical Devices.

Surface modification of thermoplastic polyurethane (TPU) could significantly enhance its suitability for biomedical devices and public health products. Nevertheless, customized modification of polyurethane surfaces with robust interfacial bonding and diverse functions via a simple method remains an enormous challenge. Herein, a novel thermoplastic polyurethane with a photoinitiated benzophenone unit (BPTPU) is designed and synthesized, which can directly grow functional hydrogel coating on polyurethane (PU) in situ by initiating polymerization of diverse monomers under ultraviolet irradiation, without the involvement of organic solvent. The resulting coating not only exhibits tissue-like softness, controllable thickness, lubrication, and robust adhesion strength but also provides customized functions (i.e., antifouling, stimuli-responsive, antibacterial, and fluorescence emission) to the original passive polymer substrates. Importantly, BPTPU can be blended with commercial TPU to produce the BPTPU-based tube by an extruder. Only a trace amount of BPTPU can endow the tube with good photoinitiated capacity. As a proof of concept, the hydrophilic hydrogel-coated BPTPU is shown to mitigate foreign body response in vivo and prevent thrombus formation in rat blood circulation without anticoagulants in vitro. This work offers a new strategy to guide the design of functional polyurethane, an elastomer-hydrogel composite, and holds great prospects for clinical translation.

Machine Perfusion Deters Ischemia-Related Derangement of a Rodent Free Flap: Development of a Model

IntroductionMachine perfusion can enable isolated support of composite tissues, such as free flaps. The goal of perfusion in this setting is to preserve tissues prior to transplantation or provide transient support at the wound bed. This study aimed to establish a rodent model of machine perfusion in a fasciocutaneous-free flap to serve as an affordable testbed and determine the potential of the developed support protocol to deter ischemia-related metabolic derangement. MethodsRat epigastric-free flaps were harvested and transferred to a closed circuit that provides circulatory and respiratory support. Whole rat blood was recirculated for 8 h, while adjusting the flow rate to maintain arterial-like perfusion pressures. Blood samples were collected during support. Extracellular tissue lactate and glucose levels were characterized with a microdialysis probe and compared with warm ischemic, cold ischemic, and anastomosed-free flap controls. ResultsMaintenance of physiologic arterial pressures (85-100 mmHg) resulted in average pump flow rates of 360–430 μL/min. Blood-based measurements showed maintained glucose and oxygen consumption throughout machine perfusion. Average normalized lactate to glucose ratio for the perfused flaps was 5-32-fold lower than that for the warm ischemic flap controls during hours 2-8 (P < 0.05). ConclusionsWe developed a rat model of ex vivo machine perfusion of a fasciocutaneous-free flap with maintained stable flow and tissue metabolic activity for 8 h. This model can be used to assess critical elements of support in this setting as well as explore other novel therapies and technologies to improve free tissue transfer.

Discovery of BT-114143, a Novel and Potent Small-Molecule Plasminogen Inhibitor for Hyperfibrinolysis

Blood coagulation and fibrinolysis are essential physiological functions, whose dysregulation is a life-threatening emergent situation requiring immediate medical intervention. In particular, hyperfibrinolysis-triggered bleeding occurs in certain medical conditions such as postpartum hemorrhage (PPH) or during perioperative procedures, natural disasters, traumatic accidents as well as battlefield situations, and is one of the major causes of mortalities worldwide during peacetime and war. Tranexamic acid (TXA) has been widely used as an antifibrinolytic drug since 1960s, however, the low potency of TXA has limited its clinical applications. Here, we have developed BT-114143, a novel and potent small-molecule plasminogen inhibitor. BT-114143 exhibited over four-fold higher affinity for recombinant human plasminogen than TXA in surface plasmon resonance (SPR) analysis. Similarly, affinity of BT-114143 was at least one magnitude higher than that of either epsilon-aminocaproic acid (EACA) or p-aminomethylbenzoic acid (PAMBA) (Table 1). In vivo efficacy studies were conducted in recombinant tissue plasminogen activator (rt-PA)-triggered rat tail bleeding model and rabbit liver bleeding model by hepatectomy. BT-114143 reduced bleeding time dose-dependently in both animal models, but also exhibited similar potency as compared to TXA. Similar potency between BT-114143 and TXA was further confirmed by rt-PA triggered fibrinolysis in either rat or rabbit whole blood in thromboelastography (TEG) assay, suggesting interspecies difference in response to bleeding. However, ex vivo studies on human plasma clot lysis assay and human whole blood TEG assay (Figure 1) demonstrated nearly ten-fold antifibrinolytic potency as compared to TXA, suggesting superior efficacy for treatment of hyperfibrinolysis-related bleedings. In addition, a panel of GLP toxicology studies has confirmed the preclinical safety of BT-114143. Moreover, electrophysiological analysis has demonstrated comparable inhibitory effect of BT-114143 and TXA on GABA A receptor and Glycine receptor. At present, BT-114143 is undergoing phase I clinical study in China (CTR20222910) and is expected to apply for FDA approval for clinical trial in 2024. Furthermore, BT-114143 is being developed for intramuscular (i.m.) injection, making it more suitable for emergency situations including PPH, traumatic injuries, natural disasters, and combat injuries.

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (i.p. 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* p < 0.05 and ** p < 0.01 vs. baseline; n = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism

The effect of uridine (30 mg/kg for 7 days; intraperitoneally) on the functions of liver mitochondria in rats with experimentally induced hyperthyroidism (HT) (200 µg/100 g for 7 days, intraperitoneally) is studied in this paper. An excess of thyroid hormones (THs) led to an intensification of energy metabolism, the development of oxidative stress, a significant increase in the biogenesis, and changes in the content of proteins responsible for the fusion and fission of mitochondria. The injection of uridine did not change the concentration of THs in the blood of hyperthyroid rats (HRs) but normalized their body weight. The exposure to uridine improved the parameters of oxidative phosphorylation and corrected the activity of some complexes of the electron transport chain (ETC) in the liver mitochondria of HRs. The analysis of ETC complexes showed that the level of CI–CV did not change by the action of uridine in rats with the condition of HT. The application of uridine caused a significant increase in the activity of superoxide dismutase and lowered the rate of hydrogen peroxide production. It was found that uridine affected mitochondrial biogenesis by increasing the expression of the genes Ppargc1a and NRF1 and diminishing the expression of the Parkin gene responsible for mitophagy compared with the control animals. In addition, the mRNA level of the OPA1 gene was restored, which may indicate an improvement in the ETC activity and oxidative phosphorylation in the mitochondria of HR. As a whole, the results obtained demonstrate that uridine has a protective effect against HT-mediated functional disorders in the metabolism of rat liver mitochondria.

Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability

Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs). Neuron- and oligodendrocyte-derived Nogo-A containing EVs inhibited fibroblast spreading, and this effect was partially reversed by Nogo-A receptor S1PR2 blockage. EVs purified from HEK cells only inhibited fibroblast spreading upon Nogo-A over-expression. Nogo-A-containing EVs were found in vivo in the blood of healthy mice and rats, as well as in human plasma. Blood Nogo-A concentrations were elevated after acute stroke lesions in mice and rats. Nogo-A active peptides decreased barrier integrity in an in vitro blood-brain barrier model. Stroked mice showed increased dye permeability in peripheral organs when tested 2 weeks after injury. In the Miles assay, an in vivo test to assess leakage of the skin vasculature, a Nogo-A active peptide increased dye permeability. These findings suggest that blood borne, possibly EV-associated Nogo-A could exert long-range regulatory actions on vascular permeability.

Potential Utility Of 2-(2-(5-Nitro-1-H-Benzo[D]Thiazole-2-Yl) Vinyl)-4H-6-Chloro Chromene-4-One to Mitigate the Toxic Impact of Xenobiotics in Mammals

This research aimed to investigate the individual and combined effects of two substances, 2-(2-(5-nitro-1-H-benzo[d]thiazole-2-yl) vinyl)-4H-6-Chloro Chromene-4-one referred as S1 and 2-(2-(5-nitro-1-H-benzo[d]thiazole-2-yl) vinyl)-4H Chromene-4-one referred as S2, on the survival of rats and the characteristics of total mRNA involved in molecular genetic processes in these animals. The study was conducted using Wistar Han (SPF) rats. S1, when administered at doses of 13 and 0.013 mg/kg body weight, which correspond to 1/100 and 1/100000 of the lethal dose (DL50), did not result in any clinical signs of intoxication in the rats. S1 was found to increase the level of hybridization in mRNA preparations obtained from both rat liver and blood cells. This effect was more pronounced at the higher dose of 13 mg/kg body weight compared to the lower dose of 0.013 mg/kg body weight. In contrast, when rats were exposed to S2 at a dose of 540 mg/kg body weight, equivalent to 1 DL50, pronounced intoxication was observed after 6 hours, leading to a 40% mortality rate among the animals. Interestingly, when rats were first intraperitoneally administered S1, followed by oral administration of S2 at the same doses (after 24 hours), the rats remained viable. Furthermore, the degree of hybridization of cytoplasmic mRNA with [ɑ32P]-cDNA only showed a slight decrease by the end of the second day. By the third day, the overall condition of the animals had returned to normal. This combined treatment also resulted in an increase in the degree of hybridization between the mRNA molecules isolated from control rats and [ɑ32P]-cDNA obtained from the experimental group. In summary, this study suggests that S1, even at higher doses, does not induce intoxication in rats and can enhance mRNA hybridization. Furthermore, when administered before S2, it appears to protect the rats from the toxic effects of S2, as indicated by their improved survival and the recovery of molecular genetic processes.

Identification of Sanguinarine Metabolites in Rats Using UPLC-Q-TOF-MS/MS.

Sanguinarine (SAN), as the main active component of a traditional Chinese veterinary medicine, has been widely used in the animal husbandry and breeding industry. However, the metabolites of SA are still uncertain. Therefore, this research aimed to investigate the metabolites of SA based on rats in vivo. The blood, feces, and urine of rats were collected after the oral administration of 40 mg/kg SAN. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) was employed to identify the metabolites of SAN. The elemental composition of sanguinarine metabolites was inferred by analyzing their exact molecular weight, and the structures of the metabolites were predicted based on their fragment ions and cleavage pathways. A total of 12 metabolites were identified, including three metabolites in the plasma, four in the urine, and nine in the feces. According to the possible metabolic pathways deduced in this study, SAN was mainly metabolized through reduction, oxidation, demethylation, hydroxylation, and glucuronidation. This present research has summarized the metabolism of SAN in rats, which is helpful for further studying the metabolic mechanism of SAN in vivo and in vitro.

Distribution of molybdenum in soft tissues and blood of rats after intratracheal instillation of molybdenum(IV) sulfide nano- and microparticles

There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg−1 b.w.) and higher (5 mg Mo kg−1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS2-NPs) and microparticles (MoS2-MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS2-MPs and MoS2-NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS2-NPs and MoS2-MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS2-NPs compared to MoS2-MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.

Intestinal and Renal Adaptations to Changes of Dietary Phosphate Concentrations in Rat.

We have studied the role of the intestine, kidney, and several hormones when adapting to changes in dietary P concentration. Normal and parathyroidectomized (PTX) rats were fed pH-matched diets containing 0.1%, 0.6%, and 1.2% P concentrations. 32Pi uptake was determined in the jejunum and kidney cortex brush border membrane vesicles. Several hormone and ion concentrations were determined in the blood and urine of rats. Both jejunum and kidney cortex Pi transport was regulated with 5 d of chronic feeding of P diets in normal rats. Acute adaptation was determined by switching foods on day 6, which was only clearly observed in the kidney cortex of normal rats, with more statistical variability in the jejunum. However, no paradoxical increase of Pi uptake in the jejunum was reproduced after the acute switch to the 1.2% P diet. Pi uptake in the jejunum was parathyroid hormone (PTH)-independent, but in the kidney, the chronic adaptation was reduced, and no acute dietary adaptations were observed. The NaPi2a protein was more abundant in the PTX than the sham kidneys, but contrary to the modest or absent changes in Pi uptake adaptation, the transporter was similarly regulated by dietary P, as in the sham rats. PTH and fibroblast growth factor 23 (FGF23) were the only hormones regulated by all diet changes, even in fasting animals, which exhibited regulated Pi transport despite similar phosphatemia. Evidence of Pi appetite effects was also observed. In brief, our results show new characteristics of Pi adaptations, including a lack of correlation between Pi transport, NaPi2a expression, and PTH/FGF23 concentrations.

Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLC[sbnd]HRMS

LN005, as a peptide-drug conjugate (PDC), is a conjugate of the homing peptide VAP and doxorubicin (DOX). The exceptional targeting ability of the homing peptide VAP is directed toward glucose-regulated protein (GRP78), a highly expressed protein primarily found in the endoplasmic reticulum of various solid tumors. However, there are limited reports regarding the metabolism of peptide-drug conjugates (PDCs), and the in vivo metabolism of LN005 has yet to be investigated. After intravenous injection of 18 mg/kg LN005 in SD rats, biological samples including plasma, urine, fecal, and bile samples, were collected and analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). A total of 11 possible metabolites of LN005 were identified. Unchanged LN005 was found to be the main component in rat blood and urine, accounting for 46.46% and 63.79% of the total peak areas, respectively. M1057 was the most abundant metabolite in feces, accounting for 57.65% of the total peak area. Only one metabolite, M398, was identified in rat bile. The metabolism of LN005 is closely related to DOX, and the primary metabolic pathways involved oxidative deamination or hydrolysis, reductive glycosidic cleavage, hydrolytic glycosidic cleavage, and dehydrogenation.

Preclinical Hemotoxicological Profile Investigations of an Ayurvedic Medication Following Long-Term Adminidration to Male Sprague-Dawley Rats

Kutajarista (KTJ) is an Ayurvedic preparation used as a traditional medicine in ulcerative colitis in the rural population. A self-made alcoholic preparation derived from the Indian Medical System known as Kutajarishta. The main ingredient in this polyherbal combination is Holarrhena antidysenterica Wall. Ex DC (Family: Apocynaceae). It is used to treat gastrointestinal disorders, diarrhea, and amebic dysentery. Ayurvedic practitioners have been using Kutaja formulations for centuries, as they have been found to be quite helpful clinically in certain diseases. This study was conducted using mainly old literature as a basis method. At a dose of 40 milliliters per kilogram, KTJ was given chronically to male Sprague-Dawley rats in order to determine its toxicological characteristics. Following a continuous 28-day KTJ preparation administration, the following toxicological alterations were observed. Several erythrocytic parameters were found in this experiment. The anemia panel studies' findings are as follows: The total amount of red blood cells in the male rat has decreased by [7.98%]. This drop was noticeable (p=0.083) even if it was not statistically significant. There is a [8.08 %] decrease in the Hemoglobin content of the blood of the male rat, the decrease though not significant yet it was prominent (p=0.097). There is a [8.03 %] decrease in the Hematocrit level of the blood of the male rat, the decrease though not significant yet it was prominent (p=0.072). There is a statistically insignificant (p=0.882) [0.19 %] increase in the Mean corpuscular volume, a red cell index of the male rat. There is a statistically insignificant (p=0.420) [3.02 %] decrease in the Mean corpuscular hemoglobin, a red cell index of the male rat. A statistically insignificant (p=0.203) [8.50 %] increase in the red cell volume distribution width, a red cell index of the male rat, is observed, along with a negligible [3.01 %] decrease in the Mean corpuscular hemoglobin concentration, a red cell index of the male rat, which was statistically not at all significant (p=0.561).