Mielosupresión inducida por linezolid: un caso pediátrico / Myelosupression induced by linezolid: a pediatric case

El linezolid es un antibiótico de la familia de las oxazolidinonas, que actúa inhibiendo la síntesis proteica. Se emplea en infecciones graves por cocos Gram-positivos multirresistentes. Sus principales efectos secundarios son los gastrointestinales y, con menor frecuencia, la neuropatía periférica, la acidosis láctica y la mielosupresión. Se presenta el caso clínico de un niño de 12 años con diagnóstico de osteoartritis séptica de cadera derecha con osteomielitis femoral en tratamiento con linezolid, que presentó un cuadro de intolerancia digestiva, asociado a astenia y pérdida de peso. Presentaba, además, anemia normocítica, junto con leucopenia y trombopenia leves, con datos sugestivos de alteración de la hematopoyesis en el frotis sanguíneo, sugerente de toxicidad por fármacos. El cuadro se resolvió con la interrupción de la administración del fármaco. La mielosupresión reversible asociada a linezolid se relaciona con tratamientos prolongados (> 28 días), por lo que son necesarios los controles hematológicos periódicos durante ellos.

Linezolid is an antibiotic of oxazolidinones family that inhibits proteical synthesis. It is used in several Gram-positive multirresistent infections. Its more frequent side effects are gastrointestinal, followed by peripheral neuropathy and myelosuppression. We report the case of a 12-year-old boy diagnosed with septic osteoarthritis of the hip and femoral osteomyelitis, following treatment with linezolid, who complained about digestive intolerance and weight loss. He showed severe normocytic anemia and mild leukopenia and thrombocytopenia with data of hematopoiesis disorder in the blood smear that suggested drug toxicity. These findings reverted when the treatment was discontinued. Reversible myelosuppression associated with linezolid is related to long treatments (more than 28 days). So it is necessary to check the blood count during long treatments.

High consumption of sucrose induces DNA damage in male Wistar rats

ABSTRACT The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

Efecto de las nanopartículas industriales TiO 2 , SiO 2 y ZnO sobre la viabilidad celular y expresión génica en médula ósea roja de mus musculus / Effect of the Industrial Nanoparticles TiO 2 , SiO 2 and ZnO on Cell Viability and Gene Expression in Red Bone Marrow of Mus Musculus

RESUMEN Objetivos Evaluar el efecto de las nanopartículas de ZnO, TiO2 y SiO2 sobre la viabilidad celular y la expresión génica de las interleuquinas 7 y 3 y del factor estimulante de colonias de granulocito - macrófago (GM-CSF) en Mus musculus. Materiales y métodos Se extrajo médula ósea roja de cinco roedores (Balb/c) para el estudio de viabilidad celular mediante la prueba de MTT. Por otro lado, grupos cinco roedores fueron inoculados vía intraperitoneal con dosis de 0,5; 1; 2,5; 5 y 10 mg/kg de nanopartículas de ZnO y SiO2 y de 5; 10; 15; 20 y 25 mg/kg de nanopartículas de TiO2, 30 h después, se obtuvo el ARN a partir de la médula ósea roja para los análisis de expresión génica empleando las técnicas de PCR y RT-PCR cuantitativa. Resultados Las nanopartículas de ZnO y SiO2 redujeron la viabilidad celular de una manera dosis-dependiente en un 37 y 26%, respectivamente, a partir de una dosis de 1 mg/kg. En cuanto al efecto sobre la expresión génica, a las dosis 5 y 10 mg/kg, las nanopartículas de TiO2 redujeron en mayor porcentaje la expresión de las interleuquinas 7 y 3 (55,3 y 70,2% respectivamente), con respecto a la expresión del GM-CSF, el mayor porcentaje de reducción lo produjo las nanopartículas de SiO2 (91%). Las nanopartículas de ZnO redujeron a partir de las dosis de 20 y 25 mg/kg. Conclusiones Las nanopartículas de ZnO, SiO2 y TiO2 alteran la viabilidad celular y la expresión génica en la médula ósea de ratón.

ABSTRACT Objectives To evaluate the effect of ZnO, TiO2 and SiO2 nanoparticles on cell viability and expression of the interleukin 7, interleukin 3, and granulocyte-macrophage colony stimulating factor (GM-CSF) genes in Mus musculus. Material and methods Red bone marrow was extracted from five Balb/c mice for the analysis of cell viability using the MTT test. The mice were divided into two groups of five each: one group was inoculated intraperitoneally with 0.5, 1.0, 2.5, 5.0, and 10 mg/kg of ZnO and SiO2 nanoparticles, respectively, and the other group was inoculated with 5.0, 10.0, 15.0, 20.0, and 25 mg/kg of TiO2 nanoparticles, respectively. Thirty hours later, RNA was extracted from the red bone marrow of the mice in both groups for gene expression analysis using quantitative PCR and RT-PCR. Results ZnO and SiO2 nanoparticles reduced cell viability in a dose-dependent manner by 37% and 26%, respectively, starting at a dose of 1 mg/kg. TiO2 nanoparticles at 5 mg/kg and 10 mg/kg reduced the gene expression of interleukins 7 and 3 by 55.3% and 70.2%, respectively, and SiO2 nanoparticles caused the greatest decrease (91%) in the expression of GM-CSF. ZnO nanoparticles reduced the expression of GM-CSF starting at doses of 20 mg/kg and 25 mg/kg. Conclusions ZnO, SiO2 and TiO2 nanoparticles affect cell viability and gene expression in the mouse bone marrow.

Quality of life/spirituality, religion and personal beliefs of adult and elderly chronic kidney patients under hemodialysis / Qualidade de vida/espiritualidade, religião e crenças pessoais de adultos e idosos renais crônicos em hemodiálise / Calidad de vida/espiritualidad, religión y creencias personales de adultos y ancianos renales crónicos en hemodiálisis

OBJECTIVE: to assess the quality of life of chronic kidney patients undergoing hemodialysis, using the WHOQOL-bref and WHOQOL-SRPB. METHOD: a descriptive and cross-sectional study was undertaken at a kidney replacement therapy service in the interior of the state of SP. The 110subjects who complied with the inclusion criteria answered the Subject Characterization Instrument, the WHOQOL-bref and WHOQOL-SRPB. RESULTS: most of the respondents were male (67.27%), with a mean age of 55.65 years, Catholic (55.45%), with unfinished primary education (33.64%) and without formal occupation (79.08%). The WHOQOL-bref domains with the highest and lowest mean score were, respectively, "psychological" (µ=74.20) and "physical" (µ=61.14). The WHOQOL-SRPB domains with the highest and lowest mean score were, respectively, "completeness and integration" (µ=4.00) and "faith" (µ=4.40). CONCLUSIONS: the respondents showed high quality of life scores, specifically in the dimensions related to spirituality, religion and personal beliefs. Losses were evidenced in the physical domain of quality of life, possibly due to the changes resulting from the chronic kidney disease and hemodialysis treatment. .

OBJETIVO: avaliar a qualidade de vida de pacientes renais crônicos em hemodiálise, por meio do WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. MÉTODO: trata-se de um estudo descritivo, de corte transversal, realizado em uma unidade de terapia renal substitutiva do interior do Estado de São Paulo. Os 110 sujeitos que atenderam os critérios de inclusão responderam ao Instrumento de Caracterização dos Sujeitos, ao WHOQOL-bref e WHOQOL-Spirituality, Religion and Personal Beliefs. RESULTADOS: a maioria dos respondentes era do sexo masculino (67,27%), com idade média de 55,65 anos, católica (55,45%), com ensino fundamental incompleto (33,64%) e sem ocupação formal (79,08%). Os domínios do WHOQOL-bref com maior e menor pontuação média foram, respectivamente, "psicológico" (µ=74,20) e "físico" (µ=61,14). Os domínios do WHOQOL-Spirituality, Religion and Personal Beliefs de menor e maior pontuação média foram, respectivamente, "totalidade e integração" (µ=4,00) e "fé" (µ=4,40). CONCLUSÕES: os respondentes apresentaram elevados escores de qualidade de vida, especificamente nas dimensões referentes à espiritualidade, religião e crenças pessoais. Evidenciaram-se prejuízos no domínio físico da qualidade de vida, possivelmente em decorrência das alterações resultantes da doença renal crônica e do tratamento hemodialítico. .

OBJETIVO: evaluar la calidad de vida de pacientes renales crónicos en hemodiálisis, por medio del WHOQOL-bref y WHOQOL-SRPB. MÉTODO: se trata de un estudio descriptivo, de corte transversal, realizado en una unidad de terapia renal substitutiva del interior del estado de SP. Los 110 sujetos que atendieron a los criterios de inclusión respondieron al Instrumento de Caracterización de los Sujetos, al WHOQOL-bref y WHOQOL-SRPB. RESULTADOS: la mayoría de los entrevistados era del sexo masculino (67,27%), con edad promedio de 55,65 años, católicos (55,45%), con enseñanza fundamental incompleta (33,64%) y sin ocupación formal (79,08%). Los dominios del WHOQOL-bref con mayor y menor puntuación promedio fueron, respectivamente: "psicológico" (µ=74,20) y "físico" (µ=61,14). Los dominios del WHOQOL-SRPB de menor y mayor puntuación promedio fueron, respectivamente: "totalidad e integración" (µ=4,00) y "fe" (µ=4,40). CONCLUSIONES: los entrevistados presentaron elevados puntajes de calidad de vida, específicamente en las dimensiones referentes a espiritualidad, religión y creencias personales. Se evidenciaron perjuicios en el dominio físico de la calidad de vida, posiblemente en consecuencia de las alteraciones resultantes de la enfermedad renal crónica y del tratamiento de hemodiálisis. .

Assessment of methyl methacrylate genotoxicity by the micronucleus test

The aim of this study was to evaluate the genotoxic potential of methyl methacrylate (MMA) vapor by simulating standard occupational exposure of 8 hours per day and using the micronucleus test. We used 32 adult male Wistar rats divided into three groups: A - 16 rats exposed to MMA for 8 hours a day, B - Eight rats receiving single subcutaneous doses of cyclophosphamide on the first day of the experiment (positive control), C - Eight rats receiving only water and food ad libitum (negative control). Eight rats from group A and all of the rats from groups B and C were sacrificed 24 hours after beginning the experiment (acute exposure in group A). The remaining animals in group A were sacrificed 5 days after the experiment began (repeated exposure assessment in group A, simulating occupational exposure 40 hours/week). Femoral bone marrow was collected from each rat at the time of sacrifice for use in the micronucleus test. Two slides were completed per animal and were stained with Giemsa staining. Two thousand polychromatic erythrocytes were counted per animal. The Kruskal-Wallis test followed by a multiple comparisons test (Dunn test) was used for statistical analysis. The median number of micronuclei was 7.00 in the group exposed to MMA for 1 day, 2.00 in the group exposed to MMA for 5 days, 9.00 in the group exposed to cyclophosphamide (positive control) and 0.756 in the negative control group (p < 0.0001). MMA was genotoxic when measured after 1 day of exposure but was not evidently genotoxic after 5 days.

Changes in morphology of long bone marrow tissue of rats submitted to cryotherapy with liquid nitrogen / Alterações na morfologia do tecido medular de ossos longos de ratos submetido à crioterapia com nitrogênio líquido

PURPOSE: To study the main effects of local use of liquid nitrogen on bone marrow tissue in rats. METHODS: The femoral diaphyses of 42 Wistar rats were exposed to three local and sequential applications of liquid nitrogen for one or two minutes, intercalated with periods of five minutes of passive thawing. The animals were sacrificed after one, two, four and 12 weeks and the specimens obtained were analyzed histomorphologically. RESULTS: In the second experimental week of one-minute protocol, histological degree of inflammation obtained a mean score of one (mild), ranging from 0 (absent or scarce) and two (moderate) (Kruskal-Wallis test p=0.01). In the second experimental week of two-minute protocol, degree of inflammation to the medullar tissue obtained an average score of two (Kruskal-Wallis test p=0.01). CONCLUSION: The degree of inflammation of the bone marrow tissue was higher in protocol of three applications of two minutes compared to protocol of three applications of one minute.

OBJETIVO: Investigar os principais efeitos do uso local de nitrogênio líquido sobre o tecido medular ósseo em ratos. MÉTODOS: As diáfises femorais de 42 ratos Wistar foram expostas a três aplicações sequenciais locais de nitrogênio líquido por um ou dois minutos, intercaladas por períodos de cinco minutos de degelo espontâneo. Os animais foram sacrificados após uma, duas, quatro e 12 semanas e os espécimes obtidos foram analisados histomorfologicamente. RESULTADOS: Na segunda semana experimental do protocolo de um minuto, o grau histológico de inflamação obteve um escore médio de um (leve) variando entre 0 (ausente ou escarço) a dois (moderado) (Teste de Kruskal-Wallis p=0.01). Na segunda semana experimental do protocolo de dois minutos, o grau histológico de inflamação do tecido medular obteve um escore máximo de dois (moderado) (Teste de Kruskal-Wallis p=0.01). CONCLUSÃO: O grau de inflamação do tecido medular ósseo foi maior no protocolo de três aplicações de dois minutos comparado ao protocolo de três aplicações de um minuto.

Chronic ethanol consumption in mice does not induce DNA damage in somatic or germ cells, evaluated by the bone marrow micronucleous assay and the dominant lethal mutation assay

Although alcohol is known to be a carcinogen for humans, ethanol-genotoxicity studies are incomplete. Ethanol seems not to be a bacterial mutagen, but the results are conflicting in rodent assays. We investigate the genotoxicity in the bone marrow micronucleus (MN) test and in the dominant lethal mutation (DLM) assay using two long-term ethanol exposure protocols. In the MN test, mice consumed three doses (5, 10 and 15% v/v) for 32 weeks. MN induction was compared to two control groups of 5- and 38-week-old mice (the ages of the treated mice when the treatment was initiated and when they were killed, respectively). For the three groups treated with ethanol there was no significant increase in MN induction as compared to the first control group, but observed MN frequencies were significantly lower than in the 38-week-old control group. This suggests a protective effect against genotoxic damage caused by aging, probably due to ethanol action as a hydroxyl radical scavenger. In the DLM assay, male mice drank ethanol at 15% or 30% (v/v) for 20 weeks. In both groups the number of dead implants was similar to the control, but there was a significant reduction in total implants, indicating a pre-implantation loss.

Assessment of fibrosis and vascularization of bone marrow stroma of chronic myeloid Leukemia patients treated with imatinib mesylate and their relationship with the cytogenetic response / Avaliação da fibrose e vascularização do estroma da medula óssea de pacientes com leucemia mielóide crônica tratados com mesilato de imatinibe e sua relação com a resposta citogenética

Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22), resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM), which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR) and bone marrow biopsies (BMB) were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27 percent of the patients. The results from the initial BMB analysis showed that 59.09 percent presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17 percent presented this degree. With regard to vascularization of the initial sample, 90.91 percent were graded between II and IV, whereas after treatment, 40.91 percent had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.

A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22), que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI), o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC) e as biópsias de medula óssea (BMO) antes e após o tratamento com MI. As BMO foram avaliadas quanto ao grau de reticulina e vascularização. Os resultados correlacionaram-se com a RC cujo tempo médio para obtenção da RC foi de 9 meses, sendo atingida por 77.27 por cento dos pacientes. Na primeira BMO, 59.09 por cento dos pacientes apresentaram grau de reticulina entre 2+ e 4+ e após o tratamento, apenas 27.17 por cento apresentaram esta graduação. Quanto à vascularização da primeira amostra, 90.91 por cento foram graduadas entre II e IV e após o tratamento, 40.91 por cento apresentaram esta graduação. Os resultados sugerem uma correlação diretamente proporcional entre os graus de reticulina e vascularização com a RC.

Evaluation of vascular endothelial growth factor (VEGF) in interradicular bone marrow in olpadronate treated animals

Vascular endothelial growth factor (VEGF) is a protein that increases vascular permeability and induces the proliferation, migration and survival of endothelial cells. Bisphosphonates (BPs) are antiresorptive drugs that are widely used in the treatment of bone metabolism diseases and bone metastases. Since 2003, cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have been reported. Few papers explain the mechanisms that induce BRONJ; some authors mention alterations in bone remodelling and a certain antiangiogenic effect of BPs. The aim of this study is to evaluate the expression of VEGF in bone marrow cells and the number of blood vessels and area occupied by them in animals treated with the BP sodium olpadronate (OPD). We used 16 Wistar rats, 60 days old, divided into two groups, experimental (OPD) and control. The OPD group received 0.3 mg/kg/week intraperitoneal OPD for 5 weeks. The control group received an equivalent intraperitoneal volume of physiological saline solution. After euthanasia, hemimandibles were processed and mesio-distal histological sections of the first molar were prepared. Sections were stained with hematoxylin-eosin (HE), immunohistochemical detection of VEGF was performed (sc- 7269) and the following histomorphometric parameters were evaluated: In HE-stained sections - number of blood vessels per sq. mm. and percentage (%) of area occupied by blood vessels in relation to total area evaluated; in sections with immunohistochemical detection of VEGF – number of VEGF+ bone marrow cells per sq. mm. Data underwent statistical analysis. Number of blood vessels/mm2 was significantly lower in the OPD group (OPD: 92 ± 16; Control: 140 ± 31; p<0.05) and % vascular area/ total area evaluated showed no significant difference (OPD: 15.6 ± 6.1; Control: 10.2 ± 4.2). Number of VEGF+ cells/mm2 was lower in the OPD group than in the control group, with statistically significant differences (OPD: 7804.8 ± 597; Control: 13187.6 ± 894; p<0.001). The results of this study suggest that monosodium olpadronate has an antiangiogenic effect. Further studies are needed to reveal its potential as an antitumor agent and its connection with the onset of BRONJ.

El factor de crecimiento vascular (VEGF) es una proteina que incrementa la permeabilidad vascular, induce la proliferacion, migracion y supervivencia de las celulas endoteliales. Los bifosfonatos (BFs) son drogas antirresortivas ampliamente utilizadas en el tratamiento de enfermedades que alteran el metabolismo oseo y de metastasis oseas. Desde el 2003 se han reportado casos de osteonecrosis de maxilar asociada al uso de BFs (ONAB). Escasas publicaciones explican los mecanismos que inducen la ONAB, algunos autores mencionan las alteraciones en la remodelacion osea y un cierto efecto antiangiogenico de los BFs. El objetivo del presente trabajo es evaluar la expresion de VEGF en celulas de la medula osea y el numero y el area ocupada por vasos sanguineos en animales tratados con el BF olpadronato monosodico (OPD). Se utilizaron 16 ratas Wistar de 60 dias divididas en dos grupos, experimental (OPD) y control. El grupo OPD, recibio 0,3 mg/kg/sem de OPD via IP, durante 5 semanas. El grupo control, recibio un volumen equivalente via IP de solucion fisiologica. Luego de practicada la eutanasia se obtuvieron las hemimandibulas y se procesaron para obtener cortes histologicos mesio-distales del primer molar. Se realizo la coloracion hematoxilina-eosina (HE) y la deteccion inmunohistoquimica de VEGF (sc-7269) y se evaluaron los siguientes parametros histomorfometricos: En cortes con H&E: Numero de vasos sanguineos por mm2 y porcentaje (%) de area ocupada por los vasos sanguineos en relacion al area total evaluada; en cortes con la deteccion inmunohistoquimica de VEGF: Numero de celulas medulares VEGF+ por mm2. Los datos fueron estadisticamente analizados. El N° vasos sanguineos/mm2 fue significativamente menor en el grupo OPD (OPD: 92 ± 16; control: 140 ± 31; p<0,05) y el % area vascular/area total evaluada no mostro diferencias significativas (OPD: 15,6 ± 6.1; Control: 10.2 ± 4.2). El N° de celulas VEGF+/mm2 en el grupo OPD fue menor que en el grupo control con diferencias estadisticamente significativas (OPD: 7804,8 ± 597; Control: 13187,6 ± 894; p<0,001). Los resultados de este estudio sugieren que el olpadronato monosodico tiene un efecto antiangiogenico. Futuros estudios revelaran su potencial como agente antitumoral asi como tambien su relacion con la aparicion de ONAB.

Cadmium affects viability of bone marrow mesenchymal stem cells through membrane impairment, intracellular calcium elevation and DNA breakage.

Background: Cadmium is an important heavy metal with occupational and environmental hazard. Cadmium toxicity results mainly in bone-related complication such as itai-itai disease. Mesenchymal stem cells of the bone marrow have the ability to differentiate to osteoblasts which ensure the well-being of the bone tissue. Thus the aim was to investigate the effect of cadmium on viability of rat bone marrow mesenchymal stem cells. Materials and Methods: The rat bone marrow mesenchymal stem cells were grown to confluency in DMEM medium supplemented with 15% fetal bovine serum and penicillin-streptomycin up to third passage. Then the cells were treated with 0, 5, 15, 25, 35, and 45 of CdCl 2 at 12, 24, 36, and 48 h, and their viability was investigated using trypan blue staining. In addition, after treatment with selected dose (15 and 45 μM) and time (24 and 48 h) the cell morphology, DNA damage and calcium content of the cells were evaluated. Data was analyzed using one and two-way ANOVA (Tukey test) and the P<0.05 was taken as the level of significant. Results: Cadmium chloride caused significant dose and time-dependent reduction of viability. In addition, morphological changes such as nuclear breakage and chromatin condensation, as well as cytoplasm shrinkage, were observed. The Comet assay showed a significant dose-dependent increase in DNA damage and also a significant increase in the intracellular levels of Ca 2+ was observed. Conclusion: Cadmium chloride is a toxic compound which might affect the well-being of bone tissue through affecting the mesenchymal stem cells.

effect of MS14 on body weight, spleen index and structures of kidney, liver, spleen, lung, lymph node and bone marrow histology in Balb/c mice

MS 14 is an Herbal-marine preparation that has been used in experimental studies for the management of Multiple sclerosis, [MS]. In this study the effect of MS 14 on body weight, spleen index and the histological picture of various organs was evaluated. Female Balb/C mice of 6-8 weeks age were divided into control and test groups. MS 14 was orally administrated at a dose of 100 mg/kg for five days to the experimental group and normal saline given to the control group. After euthanasia on day six, the body weight was measured, spleen index was calculated and representative pieces of tissues including kidney, liver, spleen, lung, lymph node and bone marrow were collected in 10% formalin solution and processed through a standard paraffin embedding method. Sections of 5 micrometer thickness were cut and stained with hematoxylin and eosin. MS 14 at 100 mg/kg did not affect body weight and spleen index, but in the test group, at least 50% of spleen and 90% of lymph node micro sections showed lymphoid hyperplasia: no reactive changes were observed in controls. In both groups, histological evaluation of kidney, liver, spleen, lung, lymph node and bone marrow micro sections showed no significant histological alterations in the normal architecture. According to result of this study, it seems that although MS 14 has no effect on body weight and spleen index, it may induce hyperplastic changes in spleen and lymph nodes, thus signaling activation of the immune system

Suppression of doxorubicin apoptotic, histopathologic, mutagenic and oxidative stress effects in male mice bone marrow and testis tissues by aqueous rosemary leaves extract

In the present set of investigations, the anti-mutagenic and anti-cytotoxic effects of aqueous rosemary leaves extract [RE] beside the dose dependency of these effects on male mice bone marrow and germ cells have been evaluated using in vivo cytogenetic, histopathologic and apoptotic assays, as well as biochemical analysis. Doxorubicin [DXR], a well-known mutagen and cytotoxic agent, was given at a single dose of 25 mg/kg b. wt. intraperitoneally at the fifteenth day. 25, 125, 250 and 375 mg/kg b. wt. of RE were given through oral intubation once a day/three days for 15 days prior to DXR administration. The animals of the positive control group [DXR alone] showed significant increase in the mutagenic effect in bone marrow cells, histological damage, incidence of apoptotic cells [TUNEL-positive cells], level of lipid peroxidation and activity of superoxide dismutase in testis. Though, the activities of the other antioxidant enzymes such as glutathione peroxidase, catalase and glutathione reduced form beside the serum level of testosterone and the rate of primary spermatocytes' transformation to spermatids were significantly declined [P < 0.001]. The ratio of dismutase to glutathione peroxidase and/or catalase was significantly elevated. Pretreatment with each dose of RE showed significant reduction in these frequency of chromosomal aberrations and mitotic index of bone marrow cells and the level of peroxidation, the ratio of SOD/ GPX or CAT, the histological damage and the incidence of apoptotic cells in testes. Also, it caused increase in the levels of some antioxidant enzymes [GSH, CAT and GPX], the level of testosterone and returned the semineferous tubular cell populations' ratio to the control distribution.The protective efficacy of the RE was much pronounced following pretreatment with 125 mg/kg b. wt

Aspirin intake suppresses MMC-induced genotoxicity in mice.

The genotoxicity induced by mitomycin C (MMC) was found to be decreased by aspirin on alkaline single cell gel electrophoresis (SCG) assay in multiple organs of mice. Aspirin at doses of 0.5, 5 and 50 mg/kg and MMC at 2 mg/kg were administered and then liver, lung, kidney, spleen, colon and bone marrow were sampled after 3 h. Significant protective effects of aspirin against MMC-induced genotoxicity was observed in all but the bone marrow, where no change was evident. The results suggest that the radical scavenging ability of aspirin prevents danage by MMC-induced reactive oxygen species (ROS) in multiple organs.

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg-1. For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg-1 of EEA and 4 mg.kg-1 of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg-1 at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg-1 co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg-1 EEA doses co-administered with 4 mg.kg-1 of MMC.

O araticum (Annona crassiflora Mart.) é uma planta tipicamente brasileira, largamente utilizada em humanos como remédio para o tratamento de diversas doenças como diarréia, reumatismo e sífilis. Esta planta contém acetogeninas que apresentam propriedades citotóxica, antitumorigênica e antiparasitária. Neste estudo, foram avaliados os possíveis efeitos mutagênico, antimutagênico e citotóxico do extrato etanólico de folhas de araticum, pelo teste de micronúcleos em camundongos. Para a investigação da atividade mutagênica, os animais foram tratados com o extrato etanólico de araticum (EEA) utilizando 10, 20, 50, 100 e 160 mg.kg-1. Para todas as doses, as freqüências de eritrócidos policromáticos micronucleados (MNPCE) foram avaliadas em 24, 48 e 72 horas após o tratamento. Para a investigação da atividade antimutagênica, os animais foram tratados com 10, 20, 50 e 100 mg.kg-1 de EEA simultaneamente com 4 mg.kg-1 de MMC. A freqüência de MNPCE foi avaliada após 36 horas de exposição. A citotoxicidade foi avaliada pela razão de eritrócitos policromáticos e normocromáticos (PCE/NCE). Na avaliação da mutagenicidade, todas as doses de EEA não aumentaram significativamente o número de MNPCE (P > 0,05), comparativamente as do grupo solvente-controle. Em relação ao tempo de administração, não foi constatada diferença significativa entre os 3 períodos avaliados (P > 0,05). Esses resultados indicam que o EEA não exerceu atividade mutagênica.A citotoxicidade foi evidente nas doses de 50, 100 e 160 mg.kg-1 em 24 e 48 horas depois da exposição. Em relação à antimutagenicidade, exceto para a dose de 10 mg.kg-1 co-administrada com 4 mg.kg-1 de MMC, todas reduziram significativamente a freqüência de MNPCE, comparativamente as do grupo controle positivo (P < 0,05). Esses resultados, portanto, indicam uma atividade antimutagênica do EEA. A citotoxicidade foi significativamente aumentada (P < 0,01) na dose de 100 mg.kg-1 de EEA co-administrada com 4 mg.kg-1 de MMC.

Anti-genotoxic effect of vitamin E administration in acrylamide intoxicated rat bone marrow cells

This study aims to investigate the effect of oral administration of vitamin E [VE, 300 mg/kg, oral intubation daily for 21 consecutive days] to normal and acrylamide-intoxicated [ACR, 25 mg/kg daily for 21 consecutive days] rats. Bone marrow was used to monitor the changes in micronucleus [MN] incidence and modulating the genotoxic effects of gavaged ACR. Treatment of rats with acrylamide [ACR] significantly elevated the frequency of bone marrow MN. Moreover, VE administration decreased the MN frequency to be near the control values; suggesting the ameliorative effect of VE against ACR toxicity

[Genotoxic effect of hydrogen peroxide on bone marrow erythrocytes of female Balb/C mouse]

Hydrogen peroxide is a strong oxidant which is being widely used in hairdresser places. Genotoxic effect of such substances, referred to as "interaction between gene and environment, is one of the most worrying problems of international health society. On the basis of the wide use of hydrogen peroxide, its capability on induction of chromosomal damages on polychromatic erythrocytes of bone marrow of exposed female Balb/C mice was investigated. The female Balb/C mice were used as experimental model. The mice were divided to three different groups including: control, Sham-exposed and experimental groups. The experimental group was exposed to inhalation of 9% oxidant vapor, containing hydrogen peroxide, for 2 and 3.5 hours per day for 7 days. Bone marrow cells of exposed as well as control and sham-exposed mice were collected using FCS, and micronucleus assay was performed. The chromosomal aberration was investigated by scoring the micronucleus containing polychromatic erythrocytes. The data was statistically analyzed by t-test. The results showed that mean No. of polychromatic erythrocytes in sham-exposed 1 and treated 1 [2 hours exposure to H2O2] were 8.87 +/- 1.01 and 5.75 +/- 3.05 respectively [P<0.05], and sham-exposed 2 and treated 2 [3.5 hours exposed to H2O2] were 8 +/- 2.36 and 42.37 +/- 4.8 respectively [P<0.01]. Also increasing the exposure treatment time with H2O2 could increase the chromosomal abnormality [P<0.05]. Results of this study revealed the genotoxic effects of inhalation of 9% H2O2 on bone marrow cells of female Balb/C mouse

Antimutagenic effects of piperine on cyclophosphamide-induced chromosome aberrations in rat bone marrow cells.

Piperine is a major pungent substance and active component of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). Both plants are used worldwide as household spices and condiments. They are also used as important ingredients in folklore medicine in many Asian countries. Therefore, it is of interest to study antimutagenic effects of piperine. In this study, its influence on chromosomes was investigated in rat bone marrow cells. Male Wistar rats were orally administered piperine at the doses of 100, 400 and 800 mg/kg body weight for 24 hours then challenged with cyclophosphamide at a dose of 50 mg/kg body weight by intraperitoneal injection. Twenty-four hours thereafter, all animals were sacrificed and bone marrow samples were collected for chromosomal analysis. The results demonstrated that piperine at a dose of 100 mg/kg body weight gave a statistically significant reduction in cyclophosphamide-induced chromosomal aberrations. In conclusion, piperine may have antimutagenic potential. The underlying molecular mechanisms now require attention.