Marrow Erythrocytes Research Articles

Effectiveness and safety of bortezomib-dexamethasone regimen in patients with multiple myeloma: A prospective observational study

Background: Bortezomib and dexamethasone (BD) regimen offers a promising therapeutic approach in multiple myeloma (MM) by inhibiting the proteolytic pathway of tumor cells. Aims and Objectives: This study aims to assess the safety profile and treatment outcomes of MM patients undergoing the BD regimen. Materials and Methods: This prospective observational study included MM patients who received BD regimen. Patients received bortezomib (1.3 mg/m2 intravenous) weekly for 4 weeks along with dexamethasone (40 mg orally) weekly for 4 weeks. Clinical assessments were performed after each cycle, and adverse drug reactions were graded according to National Cancer Institute criteria. Treatment outcomes were evaluated after the 4th cycle based on specific parameters. Results: Thirty-seven patients, with a mean age of 56.2 years, predominantly male (56.8%), were included. Common symptoms included bone pain, fatigue, weight loss, and appetite loss. Toxicities were mainly grade 1 and 2, with peripheral neuropathy (PN) being the most prevalent. The BD regimen exhibited a response rate of 65%, accompanied by significant improvements in bone marrow plasma cells, β2 microglobulin, immunoglobulin assay, and erythrocyte sedimentation rate. In addition, treatment improved performance status, in 51.4% of patients achieving scores above 90 on the Karnofsky scale. Conclusion: The BD regimen demonstrated notable efficacy and tolerability in MM treatment. However, it is associated with a higher risk of PN.

Lanthanum nitrate demonstrated no genotoxicity in the conducted tests

Given the widespread applications in industrial and agricultural production, the health effects of rare earth elements (REEs) have garnered public attention, and the genotoxicity of REEs remains unclear. In this study, we evaluated the genetic effects of lanthanum nitrate, a typical representative of REEs, with guideline-compliant in vivo and in vitro methods. Genotoxicity assays, including the Ames test, comet assay, mice bone marrow erythrocyte micronucleus test, spermatogonial chromosomal aberration test, and sperm malformation assay were conducted to assess mutagenicity, chromosomal damage, DNA damage, and sperm malformation. In the Ames test, no statistically significant increase in bacterial reverse mutation frequencies was found as compared with the negative control. Mice exposed to lanthanum nitrate did not exhibit a statistically significant increase in bone marrow erythrocyte micronucleus frequencies, spermatogonial chromosomal aberration frequencies, or sperm malformation frequencies compared to the negative control (P > 0.05). Additionally, after a 24-h treatment with lanthanum nitrate at concentrations of 1.25, 5, and 20 μg/ml, no cytotoxicity was observed in CHL cells. Furthermore, the comet assay results indicate no significant DNA damage was observed even after exposure to high doses of lanthanum nitrate (20 μg/ml). In conclusion, our findings suggest that lanthanum nitrate does not exhibit genotoxicity.

Abcb10 regulates murine hematopoietic stem cell potential and erythroid differentiation

Erythropoiesis in the adult bone marrow relies on mitochondrial membrane transporters to facilitate heme and hemoglobin production. Erythrocytes in the bone marrow are produced although the differentiation of erythroid progenitor cells that originate from hematopoietic stem cells (HSCs). Whether and how mitochondria transporters potentiate HSCs and affect their differentiation toward erythroid lineage remains unclear. Here, we show that the ATP-binding cassette (ABC) transporter 10 (Abcb10), located on the inner mitochondrial membrane, is essential for HSC maintenance and erythroid-lineage differentiation. Induced deletion of Abcb10 in adult mice significantly increased erythroid progenitor cell and decreased HSC number within the bone marrow (BM). Functionally, Abcb10-deficient HSCs exhibited significant decreases in stem cell potential but with a skew toward erythroid-lineage differentiation. Mechanistically, deletion of Abcb10 rendered HSCs with excess mitochondrial iron accumulation and oxidative stress yet without alteration in mitochondrial bioenergetic function. However, impaired hematopoiesis could not be rescued through the in vivo administration of a mitochondrial iron chelator or antioxidant to Abcb10-deficient mice. Abcb10-mediated mitochondrial iron transfer is thus pivotal for the regulation of physiologic HSC potential and erythroid-lineage differentiation.

Diagnostic Utility of Reticulocyte Hemoglobin Equivalent Parameter in the Evaluation of Microcytic Hypochromic Anemia – Our Experience from Northeast India

Background: Reticulocytes are red blood cell precursors with an average lifespan of 1–2 days. Reticulocyte hemoglobin equivalent (Ret-He) is an early marker of iron deficiency (ID) erythropoiesis and reflects real-time information regarding the synthesis of young erythrocytes in the bone marrow. The objective of this study is to determine the diagnostic utility of Ret-He in patients having microcytic hypochromic anemia in comparison with serum ferritin and iron studies. Objectives: The objective of this study is to determine the diagnostic utility of the Ret-He parameter in patients having microcytic hypochromic anemia in comparison with the serum ferritin, iron studies and its role in routine hematological screening for nutritional deficiency anemia like ID. Design and Settings: The design involves observational study. Materials and Methods: A hospital-based observational study was carried out in a referral hospital. Hematological parameters were processed using Sysmex XN1000 (Sysmex Corporation, Kobe, Japan) analyzer and were compared with Serum iron studies using biochemistry analyzer (VITROS® 250 Chemistry System) from 201 participants who presented with microcytic hypochromic anemia. Main Outcome and Measures: Relationship of Ret-He parameter and its diagnostic utility for screening of iron-deficient states. Sample Size: The sample size was 201. Results: When serum ferritin is taken as “the gold standard” to detect ID, with Ret-He cutoff of 27.15 pg/cell, we found a statistically significant positive correlation between Ret-He and serum ferritin (P < 0.001). We found a sensitivity of 57.37% and specificity of 75.95% with area under the curve of 0.681, positive predictive value of 100%, negative predictive value of 3.8%, and accuracy of 62.19% for Ret-He in detecting ID anemia (IDA). Also found a statistically significant negative correlation between Ret-He and total iron binding capacity (P < 0.001). There was no statistical correlation between Ret-He and serum iron levels in our study. Conclusions: The present study suggests Ret-He is one of the better and more reliable hematological parameters indicating ID and, when used along with biochemical parameters like serum ferritin, can give valuable inputs in a better screening and diagnosis of IDA; hence proper treatment is possible. Limitations: The multicentric study is required to standardize Ret-He reference values, and follow-up to therapy of the subjects was not done. Additional hemoglobin variant analysis data would have been favorable to the study.

Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys.

Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.

Genetic and prenatal developmental evaluation of anthraquinone

Anthraquinone is a recently identified contaminant present in teas globally, and its potential teratogenic and genotoxic impacts have yet to be fully comprehended. Hence, this study's objective was to determine anthraquinone's genotoxicity using various studies such as the Ames test, Mammalian erythrocyte micronucleus test, and in-vitro mammalian chromosome aberration study. Additionally, the study assessed its effects on maternal gestational toxicity and the fetus's teratogenicity through prenatal developmental toxicity research in rats. Results indicated that anthraquinone did not manifest mutagenic effects on Salmonella typhimurium histidine-deficient, did not cause chromosomal aberrations in Chinese hamster ovary cell subclone CHO-K1, and did not exhibit a genotoxic effect on mouse bone marrow erythrocytes. However, in the prenatal developmental toxicity study, administering anthraquinone orally to pregnant rats from day 5 to day 19 of gestation resulted in decreased body weight and food consumption of pregnant rats, along with a higher number of visceral malformations in the fetuses in the highest dose group (217.6 mg/kg BW). Additionally, two pregnant rats died in this group. The study has established the no observed adverse effect level (NOAEL) as 21.76 mg/kg BW, while the lowest observed adverse effect level (LOAEL) was 217.6 mg/kg BW.

Reducing erythroblast apoptosis in β-thalassemia via unfolded protein response (UPR) signaling

Apoptosis plays an important role in ineffective erythropoiesis in β-thalassemia. This early destruction causes severe anemia and contributes significantly to patient mortality. There are several treatment options for this disorder based on the use of drugs that inhibit the destruction of immature erythrocytes in the bone marrow. However, the clinical effectiveness of these drugs has yet to be proven. Therefore, new targets for more effective treatments are needed. The unfolded protein response (UPR) is a biological process that occurs in response to endoplasmic reticulum (ER) stress. To cope with ER stress, unfolded or misfolded proteins activate the UPR pathway, thereby activating a series of cell death pathways. Here, we propose that prolonged ER stress causes apoptosis via UPR signaling during erythroid development in β-thalassemia. Our proposed hypothesis is supported by 1) the involvement of UPR signaling in apoptotic cell death, 2) changes in UPR-related proteins in β-thalassemia, and 3) the availability of UPR signaling inhibitors. In vitro and in vivo studies should be conducted to identify the proteins that participate in the UPR pathway and identify molecular targets for therapy. The β-thalassemia mouse model could be used to evaluate the efficacy of UPR mimic drugs prior to clinical trials. If verified, gaining control over cell fate determination during UPR signaling in β-thalassemia may minimize erythroblast destruction.

Safety assessment of surfactin-producing Bacillus strains and their lipopeptides extracts in vitro and in vivo.

Beneficial Bacillus strains can be administered to livestock as probiotics to improve animal health. Cyclic lipopeptides produced by Bacillus such as surfactins may be responsible for some of the beneficial effects due to their anti-inflammatory and immunomodulatory activity. The aim of the present study was to isolate and evaluate the biocompatibility of native Bacillus spp. strains and their surfactin-like lipopeptides in vitro and in vivo to determine their potential to be used on animals. Biocompatibility of endospore suspensions (108 UFC/mL), and different dilutions (1:10; 1:50; 1:100; 1:500, and 1:1000) of Bacillus lipopeptide extracts containing surfactin was tested on Caco-2 cells by microculture tetrazolium-based colorimetric assay. Genotoxicity was tested on BALB/c mice (n = 6) administered 0.2 mL of endospore suspensions by the bone marrow erythrocyte micronuclei assay. All the isolates tested produced between 26.96 and 239.97 µg mL- 1 of surfactin. The lipopeptide extract (LPE) from isolate MFF1.11 demonstrated significant cytotoxicity in vitro. In contrast, LPE from MFF 2.2; MFF 2.7, TL1.11, TL 2.5, and TC12 had no cytotoxic effect (V% > 70%) on Caco-2 cells, not affecting cell viability signifficantly in most treatments. Similarly, none of the endospore suspensions affected cell viability (V% > 80%). Likewise, endospores did not cause genotoxicity on BALB/c mice. This study was elementary as a first step for a new line of research, since it allowed us to choose the safest isolates to keep working on the search of new potentially probiotic strains destined to production animals to improve their performance and health.

Expression of Key Enzymes in Glucose Metabolism in Chronic Mountain Sickness and Its Correlation with Phenotype

To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin. Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×109/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes and hemoglobin. The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717). CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.

Supplementation with sesame oil suppresses genotoxicity, hepatotoxicity and enterotoxicity induced by sodium arsenite in rats

BackgroundSesame oil, an edible essential oil, is known to be rich in unsaturated fatty acids, vitamins and lignans with several reported health-promoting benefits. Acute arsenic poisoning produces toxic hepatitis, bone marrow depression and adverse gastrointestinal responses. In this study, we investigated the protective effect of sesame seed oil (SSO) against genotoxicity, hepatotoxicity and colonic toxicity induced by sodium arsenite (SA) in Wistar rats.MethodsTwenty-eight male Wistar albino rats were randomly allocated into four groups: control, SA only (2.5 mg/kg), SA + SSO (4 ml/kg) and SSO alone for eight consecutive days. Liver function and morphology, bone marrow micronuclei induction, colonic histopathology, mucus production and immune expression of Bcl-2, carcinoembryonic antigen (CEA), MUC1 and cytokeratins AE1/AE3 were evaluated.ResultsSA provoked increased serum activities of liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and caused severely altered morphology of hepatic and colonic tissues with increased frequency of micronucleated polychromatic erythrocytes (MnPCEs/1000PCE) in the bone marrow. In addition, SA triggered increased expression of colonic CEA and MUC1 but weak Bcl-2 immunoexpression. However, cotreatment with SSO demonstrated protective activities against SA-induced damage, as indicated by significantly reduced serum ALT and AST, fewer micronucleated bone marrow erythrocytes and well-preserved hepatic and colonic morphologies compared to the SA-treated rats. Furthermore, SSO protected the colonic mucosa by boosting mucus production, elevating anti-apoptotic Bcl-2 expression and reducing CEA expression. GC–MS analysis of SSO revealed that it was predominated by linoleic acid, an omega-3 fatty acid, and tocopherols.ConclusionsOur data indicated that SSO protected the liver, colon and bone marrow potentially via anti-inflammatory and anti-apoptotic activities. The data suggest that sesame oil has potential therapeutic applications against chemical toxicities induced by arsenic.

ИССЛЕДОВАНИЕ МУТАГЕННЫХ СВОЙСТВ ПРЕПАРАТА ДИОМАСТ-КРС ПРИ МНОГОКРАТНОМ ВОЗДЕЙСТВИИ

This article considers the drug Diomast-KRS consisting of two components: component 1 - recombinant bovine interferons, component 2 - dioxidine, and vitamin A is also included in both components, from the point of view of its potential mutagenic activity with repeated use. The assessment was carried out using a micronucleus test, the experiment was performed on white non-linear laboratory mice (n=30). Five (5) experimental groups were formed, 6 individuals in each group. The study showed that in the studied doses (conditionally therapeutic and 1/10 of LD50) with repeated administration, there were no statistically significant changes in the quantitative content of micronuclei and the percentage of polychromatophilic erythrocytes in the bone marrow of experimental animals relative to control indicators. It was also shown that the use of individual components of the drug did not lead to a change in cytogenetic stability, which indicated the absence of a mutagenic effect in the drug Diomast-KRS under the studied dosing regimen.

More efficient induction of genotoxicity by high-LET Fe-particle radiation than low-LET X-ray radiation at low doses

ObjectiveTo understand differential effects on induction of genotoxicity and genomic instability (GI) by high-LET particle radiation and low-LET photon radiation, based on ground-based experiments using total body irradiation (TBI) of mice with Fe-particle radiation and X-ray radiation. MethodsTBI was delivered to C57BL/6J Jms strain female mice of 8 weeks old at a dose ranging from 0.1 to 3.0 Gy of Fe-particle radiation or at a dose ranging from 0.1 to 5.0 Gy of X-ray radiation. Induction of genotoxicity and GI by TBI was determined respectively at 1 and 2 months after exposure using frequency of micronuclei in bone marrow erythrocytes as the endpoint. Inhibition of bone marrow cell proliferation by TBI was measured as reduced erythropoiesis. Physiological conditions were also investigated. ResultsTBI, regardless of the type of radiation, caused statistically significant increase in genotoxicity at 1 month after exposure, but did not induce GI at 2 months after exposure even at higher doses (>1.0 Gy). The dose-response curve for the frequency of micronucleated polychromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7798 ​+ ​1.7889x– 0.5978x2 (R2 = 0.8109) and y ​= ​0.7421 ​+ ​1.3792x – 0.2588 x2 (R2 = 0.8081), respectively. The dose-response curve for the frequency of micronucleated normochromatic erythrocytes induced by Fe-particle radiation and X-ray radiation was y ​= ​0.7191 ​+ ​1.4545x – 0.4978x2 (R2 = 0.7047) and y ​= ​0.658 ​+ ​1.344x – 0.2531x2 (R2 = 0.7853), respectively. In general, high-LET Fe-particle radiation was more efficient in inducing genotoxicity than low-LET X-ray radiation at lower doses (<0.5 Gy). ConclusionsThese results further confirm that exposure to TBI, even at higher doses and regardless the type of radiation, does not induce GI in C57BL/6J strain mice measured as increased micronuclei in bone marrow erythrocytes. These findings indicate that radiation-induced GI is mouse strain dependent and suggest that more comprehensive studies should be done to explore the late health consequences from exposure to high-LET radiation at low doses.

Von Hipple-Lindau disease complicated with central retinal vein occlusion: a case report

BackgroundCentral Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO caused by VHL c.208G > A mutation.Case presentationA 20 s man whose left eye visual acuity gradually declined for half a year. The visual acuity of the left eye is counting fingers. Fundus examination revealed that retinal hemangioblastoma was also found in addition to typical CRVO signs such as tortuous expansion of retinal veins and flame-shaped hemorrhage of the retina. Liver tumor, cerebral infarction and erythrocytosis were found during systemic examination, and the diagnosis of polycythemia was confirmed by bone marrow smear. Furthermore, both family history and genetic analysis indicated that the patient had VHL disease caused by VHL c.208G > A. In this patient, a large number of bone marrow erythrocytes proliferated due to VHL disease, which led to the increase of blood viscosity and erythrocyte vascular adhesion, resulting in the obstruction of central retinal vein blood flow, and finally CRVO. For CRVO and its pathogenic factor polycythemia, patient received laser retinal photocoagulation and phlebotomies. After a 1-year follow-up, the vision in the left eye improved to 0.2 logMAR.ConclusionsThis is a rare case of polycythemia complicated by CRVO in patient with VHL disease. It reminds us that the systemic disease factors should be fully considered in the diagnosis of young patients with CRVO, and that treatment requires a coordinated effort of physicians.

Characterization and mechanism of aflatoxin degradation by a novel strain of Trichoderma reesei CGMCC3.5218.

Aflatoxins, which are produced mainly by Aspergillus flavus and A. parasiticus, are recognized as the most toxic mycotoxins, which are strongly carcinogenic and pose a serious threat to human and animal health. Therefore, strategies to degrade or eliminate aflatoxins in agro-products are urgently needed. We investigated 65 Trichoderma isolates belonging to 23 species for their aflatoxin B1 (AFB1)-degrading capabilities. Trichoderma reesei CGMCC3.5218 had the best performance, and degraded 100% of 50 ng/kg AFB1 within 3 days and 87.6% of 10 μg/kg AFB1 within 5 days in a liquid-medium system. CGMCC3.5218 degraded more than 85.0% of total aflatoxins (aflatoxin B1, B2, G1, and G2) at 108.2–2323.5 ng/kg in artificially and naturally contaminated peanut, maize, and feed within 7 days. Box–Behnken design and response surface methodology showed that the optimal degradation conditions for CGMCC3.5218 were pH 6.7 and 31.3°C for 5.1 days in liquid medium. Possible functional detoxification components were analyzed, indicating that the culture supernatant of CGMCC3.5218 could efficiently degrade AFB1 (500 ng/kg) with a ratio of 91.8%, compared with 19.5 and 8.9% by intracellular components and mycelial adsorption, respectively. The aflatoxin-degrading activity of the fermentation supernatant was sensitive to proteinase K and proteinase K plus sodium dodecyl sulfonate, but was stable at high temperatures, suggesting that thermostable enzymes or proteins in the fermentation supernatant played a major role in AFB1 degradation. Furthermore, toxicological experiments by a micronucleus assay in mouse bone marrow erythrocytes and by intraperitoneal injection and skin irritation tests in mice proved that the degradation products by CGMCC3.5218 were nontoxic. To the best of our knowledge, this is the first comprehensive study on Trichoderma aflatoxin detoxification, and the candidate strain T. reesei CGMCC3.5218 has high efficient and environment-friendly characteristics, and qualifies as a potential biological detoxifier for application in aflatoxin removal from contaminated feeds.

Hepatoprotective effect of the radiation countermeasure flagellin in the long term after irradiation of mice

Purpose Purpose is to study the hepatoprotective effect of a new promising radiation countermeasure flagellin, in the long term after irradiation. The results of the study can be useful for mitigating the consequences of man-made radiation accidents, protecting professional contingents, reducing the toxic effect of radiation therapy, and expanding the range of drug use. Materials and methods Effect of flagellin was investigated 10 months after its administration of irradiated male of mice F1 (CBAхC57Bl/6). Flagellin (0.2 mg/kg) was administrated once intraperitoneally before exposure of mice to low-intensive (10 mGy/min) γ-radiation at a dose of 12.65 Gy. The effect was evaluated in three groups: control, irradiated mice without of flagellin and with the administration flagellin 30 minutes before irradiation. Cytogenetic and cytotoxic effect in bone marrow was studied with micronucleus assay (OECD 474), in liver – with the original technique for cytome analysis of hepatocytes after fixation of liver pieces with 10% formalin, dissociation of cells with 50% KOH, staining with aceto-orcein and light green. The proportion of cells 2n, 2n + 2n, 4n, 4n + 4n, ≥8n and ≥8n + 8n was determined. Cytogenetic disorders were counted as cells with micronuclei, nuclear buds, and internuclear bridges. The ploidy index and nuclearity index were defined. Results In all studied groups of mice, the frequency of polychromatic bone marrow erythrocytes with micronuclei and hepatocytes with cytogenetic disorders did not exceed the background level. A decrease in the ploidy index of hepatocytes by 4.3 times was established 10 months after exposure to low-power ionizing radiation. In mice treated with flagellin before irradiation, the ploidy index was normalized to control. Conclusions A decrease in the ploidy of hepatocytes was revealed 10 months after exposure to a high dose of low-power ionizing radiation, which may indicate the initiation of carcinogenesis. For the first time, a new aspect of the anti-radiation effect of promising radiation countermeasure flagellin was established and its hepatoprotective properties were determined in the long term after exposure to ionizing radiation.

Evaluation of Predicting the Value of the Reticulocyte Hemoglobin Equivalent for Iron Deficiency in Chronic Kidney Disease Patients

Background: Iron management is essential for anemia treatment in chronic kidney disease. The reticulocyte hemoglobin equivalent (RET-He) is a reticulocyte parameter that reflects hemoglobin synthesis of newly formed erythrocytes in the bone marrow in real-time. Objectives: This study aims to evaluate the role of reticulocyte hemoglobin equivalent (RET-He) in predicting iron deficiency in chronic kidney disease (CKD) patients. Methods: Following a descriptive cross-sectional observational design, this study was conducted on 131 adult patients with CKD stages 3 - 5. Laboratory indices, including complete blood count, some biochemical indices, iron status, and reticulocyte indices (including RET-He), were measured. Iron deficiency (ID) was defined as TSAT &lt; 20%, where serum ferritin level &gt; 100 ng/mL was defined as functional ID, while serum ferritin level

Toxicological Assessments of a Proprietary Blend of Punica granatum Fruit Rind and Theobroma cacao Seed Extracts: Acute, Subchronic, and Genetic Toxicity Studies.

LN18178 (Tesnor®) is a standardized, proprietary composition of aqueous ethanol extracts of Punica granatum fruit rind and Theobroma cacao seeds. The present study demonstrates a broad-spectrum toxicological evaluation of LN18178 utilizing in vitro and in vivo preclinical models following the Organization for Economic Cooperation and Development (OECD) guidelines for testing chemicals. Wistar rats did not show any clinical signs of toxicity and morbidity in acute oral and dermal toxicity tests with the median lethal dose (LD50) values of at least 5000 mg/kg and 2000 mg/kg body weight, respectively. LN18178 was nonirritating to the skin and eyes of the treated rabbits. In a ninety-day subchronic repeated oral dose toxicity study, the LN18178-treated Wistar rats did not show dose-related signs of toxicity on their body weight, food consumption, organ weights, hematology, and clinical chemistry parameters. The estimated no-observed-adverse-effect level (NOAEL) of LN18178 in male and female rats was 2500 mg/kg body weight. The observations from the bacterial reverse mutation test, in vitro chromosomal aberration assay, micronucleus assay in mouse bone marrow erythrocytes, and in vitro mouse lymphoma TK+/− gene mutation assay suggest that LN18178 is neither mutagenic nor clastogenic. In summary, the present study demonstrates that oral consumption of the herbal blend LN18178 does not show signs of toxicity; also it does not elicit genetic toxicity in the standard preclinical models.

Study of Mutagenic and Antitoxic Properties of Gentabiferon-B

Abstract The combination of immunomodulators and antibiotics in the treatment of animals with diseases of bacterial etiology is one of the effective strategies for animal therapy. The drug gentabiferon-B combines antibiotic gentamicin and species-specific (bovine) recombinant interferons -α and -γ. The study aimed to evaluate the effect of course application of gentabiferon-B on the cytogenetic stability of bone marrow cells of outbred mice after administering mitomycin C (MMC). The proportion of polychromatophilic erythrocytes in the bone marrow was assessed. There was no effect of gentabiferon-B on the frequency of polychromatophilic erythrocytes with micronuclei in both healthy animals and mice with MMC-induced cytogenetic instability. The course application of gentabiferon-B before the administration of MMC led to an increase in the proportion of polychromatophilic erythrocytes (46.03±2.61%) which was non-significantly different than the negative control group. The administration of MMC alone caused a decrease in the proportion of polychromatophilic erythrocytes to 33.33±1.83%. The antitoxic effect of gentabiferon-B led to an increase in the level of polychromatophilic erythrocytes by 38.1% compared to the group that received only MMC. Studies have shown that gentabiferon-B does not have mutagenic activity and anticlastogenic properties, however, it reduces the toxic effect of MMC. In conclusion, it is indicative that gentabiferon-B has antitoxic properties and can be safely used in animal therapy.

STUDY OF POTENTIAL MUTAGENIC PROPERTIES OF THE DRUG DIOMAST-KRS

The article presents the results of studying mutagenic activity of the two-component drug Diomast-KRS (compo-nent 1 - recombinant bovine cytokines and vitamin A, component 2 - dioxidine and vitamin A), and its components separately with a single injection by means of a micronucleus test. White laboratory mice (n=36) were selected for the experiment. They were divided into 6 groups, 6 individuals in each one. It has been found that a single use of the drug Diomast-KRS at therapeutic and high doses (1/10 of LD50) does not cause statistically significant deviations in the number of micronuclei and the percentage of polychromatophilic erythrocytes in the bone marrow of white laboratory mice relative to the control values. The components of the drug used separately also did not cause changes in cytogenetic stability in the bone marrow cells of mice. Thus, the drug Diomast-KRS does not have a pronounced mutagenic effect at the tested doses.

Safety assessment of a novel water-soluble extract of Boswellia serrata gum resin: acute toxicity, 90-day sub-chronic toxicity, Ames’ bacterial reverse mutation, and in vivo micronucleus assays

Boswellia serrata gum resin extracts have demonstrated potential benefits in alleviating joint pain and discomfort of osteoarthritis. The major objective of the present study was to assess the safety of a water-soluble B. serrata gum resin extract (LI51202F1) in diverse models of acute oral, acute dermal, primary dermal irritation, eye irritation, and 90-day sub-chronic repeated dose toxicity studies, as well as Ames’ bacterial reverse mutation assay and in vivo micronucleus assay. The acute oral and dermal toxicity studies in Sprague Dawley (SD) rats demonstrated that the median lethal dose (LD50) of LI51202F1 is >2000 mg/kg body weight (BW). The acute dermal and eye irritation tests in New Zealand white rabbits exhibited that LI51202F1 is non-irritating to the skin and mildly irritating to the eyes, respectively. The 90-days sub-chronic repeated oral dose study demonstrated that the LI51202F1-treated male and female SD rats did not show signs of toxicity on their BW, food intake, organ weights, thyroid hormones, and on the clinical pathology, gross pathology, and histopathological assessments. In male and female rats, the no-observed-adverse-effect level (NOAEL) of LI51202F1 was 500 mg/kg/day, the highest tested dose in the study. The results of the bacterial reverse mutation assay in Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA (pKM101) strains in the presence or absence of S9 metabolic activation system and a micro-nucleus assay in mouse bone marrow erythrocytes demonstrated that LI51202F1 is neither mutagenic nor clastogenic. In conclusion, under the conditions of these studies, LI51202F1 demonstrated broad-spectrum safety.