Tartrazina induce genotoxicidad en linfocitos de BALB/c Mus musculus / Tartrazine induces genotoxicity in BALB/c Mus musculus lymphocytes

RESUMEN Objetivos. Determinar el efecto genotóxico de la tartrazina en linfocitos de sangre periférica de Mus musculus BALB/c. Materiales y métodos. Se realizó un estudio experimental, a través de cinco grupos, con cinco ratones en cada uno. Se les registró el peso durante 17 semanas y, en la semana 15 se les administró suero fisiológico (control negativo), dicromato de potasio 25 mg/kg de peso corporal (pc) (control positivo) y tartrazina a dosis de 0,75 mg/kg pc, 7,5 mg/kg pc y 75 mg/kg pc, durante siete días, a excepción del control positivo que fue en dosis única. Luego, cada 24 h se obtuvo una muestra de sangre periférica de la cola y se realizó el frotis, secado y coloración. Posteriormente, se realizó el conteo de 1000 linfocitos por muestra de cada ratón, en todos los tratamientos. Resultados. Los tres tratamientos con tartrazina no causaron diferencias significativas en el peso de ratones a la semana 15, pero sí produjeron diferencias significativas en la frecuencia de linfocitos micronucleados, siendo el tratamiento con tartrazina de 75 mg/kg pc el de mayor efecto genotóxico, induciendo un promedio de 1,63 ± 0,08 linfocitos micronucleados, comparado con el control positivo que generó un promedio de 1,42 ± 0,08 linfocitos micronucleados. Conclusiones. La tartrazina produjo un efecto genotóxico, incrementando el número de linfocitos micronucleados, a dosis de 0,75; 7,5 y 75 mg/kg pc y no afecta el peso corporal durante siete días de administración en M. musculus BALB/c.

ABSTRACT Objectives. To determine the genotoxic effect of tartrazine on peripheral blood lymphocytes of BALB/c Mus musculus. Materials and methods. An experimental study was carried out using five groups, with five mice in each group. Their weight was registered for 17 weeks, and at week 15 they were administered physiological saline solution (negative control), potassium dichromate at 25 mg/kg body weight (bw) (positive control) and tartrazine at doses of 0.75 mg/kg bw, 7.5 mg/kg bw and 75 mg/kg bw, for seven days, with the exception of the positive control which was a single dose. Then, every 24 hours, a peripheral blood sample was obtained from the tail, which was then smeared, dried and stained. Subsequently, 1000 lymphocytes were counted for each sample from each mouse, for all treatment groups. Results. The three tartrazine treatments did not cause significant differences in the weight of mice at week 15, but did produce significant differences in the frequency of micronucleated lymphocytes, with the 75 mg/kg bw tartrazine treatment having the greatest genotoxic effect, inducing an average of 1.63 ± 0.08 micronucleated lymphocytes, compared to the positive control which obtained an average of 1.42 ± 0.08 micronucleated lymphocytes. Conclusions. Tartrazine produced a genotoxic effect, increasing the number of micronucleated lymphocytes, at doses of 0.75; 7.5 and 75 mg/kg bw and did not affect body weight during seven days of administration to BALB/c M. musculus.

Interaction of genetic background and exercise training intensity on endothelial function in mouse aorta

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

This study aimed to investigate the feasibility of the establishment of a human cancer xenograft model using samples from computed tomography (CT)-guided percutaneous biopsy. Fresh tumor tissues obtained from 10 cancer patients by CT-guided percutaneous biopsy were subcutaneously inoculated into NOD-Prkdcem26Il2rgem26Nju (NCG) mice to establish human patient-derived tumor xenograft (PDTX) models. The formation of first and second generation xenografts was observed, and tumor volume was recorded over time. Tumor tissue consistency between the PDTX model and primary tumors in patients was compared using H&E staining and immunohistochemistry. Pharmacodynamic tests of clinically used chemotherapeutic drugs were conducted on second generation xenografts, and their effects on tumor growth and body weight were observed. CT-guided percutaneous biopsy samples were successfully collected from 10 patients with advanced cancers. The PDTX model was established in mice using tumor samples obtained from 4 cancer patients, including one small cell carcinoma sample, two adenocarcinoma samples, and one squamous cell carcinoma sample. The success rate was 40%. The obtained PDTX model maintained a degree of differentiation, and morphological and structural characteristics were similar to primary tumors. The pharmacodynamic test of chemotherapeutic drugs in the PDTX model revealed a therapeutic effect on tumor growth, as expected. CT-guided percutaneous biopsy samples can be effectively used to establish a PDTX model, and test these chemotherapy regimens.

Comparative study of fertilization rates of C57BL/6NKorl and C57BL/6N mice obtained from two other sources / 한국실험동물학회지

C57BL/6N is the most widely used inbred mouse strain applied in a wide variety of research areas including cancer, cardiovascular biology, developmental biology, diabetes and obesity, genetics, immunology, neurobiology, and sensorineural research. To compare the fertilization rates of C57BL/6NKorl mice with two commercial C57BL/6N stocks, differences in reproductive organ structures, sperm and egg numbers, fertilization rates, and embryo development rates among C57BL/6NKorl (Korea FDA source), C57BL/6NA (USA source), and C57BL/6NB (Japan source) mice were determined. Among the stocks, no significant differences were detected in organ weight and histological structure of male and female reproductive organs, although body weight was higher in C57BL/6NKorl mice than that in the other groups. The concentration and morphology of sperm and eggs in C57BL/6NKorl mice were similar to those of C57BL/6NA and C57BL/6NB mice. Furthermore, the three stocks had similar in vitro fertilization and embryo development rates, although these rates tended to be higher in C57BL/6NB mice. Pup body weight was higher in C57BL/6NKorl and C57BL/6NB mice than that in C57BL/6NA mice. The results of the present study suggest that C57BL/6NKorl, C57BL/6NA, and C57BL/6NB mice obtained from three different sources have similar fertilization and embryo development rates, although there were slight differences in the magnitude of their responses rates.

Antioxidant activities of crude phlorotannins from Sargassum hemiphyllum / 华中科技大学学报（医学）（英德文版）

Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl4), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds.

Anti-inflammatory and analgesic effects of Bi-yuan-ling granules / 华中科技大学学报（医学）（英德文版）

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

Effect of CCM3 gene defect on lead-induced cell genotoxicity in mouse embryonic fibroblasts / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of CCM3 gene defection on lead induced cell genotoxicity in mouse embryonic fibroblasts.</p><p><b>METHODS</b>C57 female mice were mated with CCM3 gene heterozygous male mice. E13.5 embryos were taken to isolate primary mouse embryonic fibroblasts. After genotyping, wild type and heterozygous cells were treated with different doses of lead acetate. Cell viability, genotoxicity and protein expression were detected by MTS assay, CB micronucleus method and Western blot, respectively.</p><p><b>RESULTS</b>Mouse embryonic fibroblasts with lead acetate treatment for 24 h, wild-type cells 100.00 µmol/L lead acetate-treated group (69.16±1.36) and the control group (100.00±2.33) compared to cells decreased by 30%, CCM3 heterozygous type cell 100.00 µmol/L lead acetate-treated group (87.16±5.50) and the control group (100.00±2.06) compared to cells decreased by 13%, the difference was statistically significant (F values were 98.59, 82.63, P<0.001). Lead acetate treatment after 48 h, wild-type cells 100.00 µmol/L lead acetate-treated group (51.99±5.62) and the control group (100.00±3.11) compared to cells decreased by 50%, heterozygous type cells 100.00 µmol/L lead acetate treatment group (66.33±4.06) and the control group (100.00±5.72) compared to cells decreased by 35%, the differences were statistically significant (F values were 82.63, 36.86, P < 0.001). The results of CBMN test showed that with increased dose, micronucleus cell rate of two genotypes showed an increasing trend, in the wild-type cells, the micronucleus cell rate (/1 000) for the control group, 29.6±2.2, 6.25 µmol/L dose group 47.3±6.6, 25 µmol/L dose group 55.5±9.1, 100.00 µmol/L dose group 66.8±3.5; heterozygous cells micronucleus cell rate (/1 000) for the control group, 35.3±5.6, 6.25 µmol/L dose of 50.0±8.3, 25.00 µmol/L dose group 57.0±8.5, 100.00 µmol/L dose group 58.8±2.1. Micronucleus cell rates (/1 000) were significant differences, in 100.00 µmol/L dose groups of two genotypes. Western blot results showed that wild-type cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.70±0.03) was 1.32 times higher than the control group (0.53±0.07), heterozygous cells CCM3 expression 100.00 µmol/L lead acetate-treated group (0.48±0.02) was 1.77 times higher than control group that of 0.27±0.04, there was statistically significant difference (F values were 14.77, 25.74, P < 0.001); wild-type cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.69±0.03) was 1.06 times higher than the control group (0.65±0.07), heterozygous cells γ-H2AX expression 100.00 µmol/L lead acetate-treated group (0.99±0.04) was 1.55 times higher than the control group CCM3 expression levels (0.64±0.06), there was statistically significant difference (wild-type cells: F = 7.08, P = 0.012, heterozygous type cell: F = 13.49, P = 0.002).</p><p><b>CONCLUSION</b>CCM3 gene may play a role in lead-induced genetic toxicity of mouse embryonic fibroblasts, CCM3 gene-lead interactions effects on mouse embryonic fibroblasts cell toxicity.</p>

Effect of γ-secretase inhibitor on hyperoxia-induced brain white matter injury in mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of γ-secretase inhibitor (N-[N-(3,5-difluorophenacetyl)-l -alanyl]-S-phenylglycine t-butyl ester, DAPT) on hyperoxia-induced brain white matter injury in mice.</p><p><b>MWTHODS</b>Three-day-old C57BL/10J mouse pups were divided into air control (C) group, control+DAPT (10 mg/kg, injected intraperitoneally) group, hyperoxia group (exposed to 80% oxygen for 48 h), and hyperoxia+DAPT group. The brain and body weights of the mice were measured at postnatal days 3, 5, 12, and 28. Real-time PCR was used to detect Notch intracellular domain (NICD) mRNA expression in the brain after modeling, and the expressions of NG2 and myelin basic protein (MBP) were detected by double-labeled immunofluorescence assay to verify the oligdendrocycle type at postnatal day 12. The mice in each group were bred until postnatal day 28 for Morris water maze test.</p><p><b>RESULTS</b>The brain and body weights were significantly decreased in mice in hyperoxia group compared to the control mice, but increased significantly after DAPT treatment (P<0.05). Real-time PCR showed that a 48-hour hyperoxia exposure significantly increased NICD mRNA expression in the brain (P<0.05), which was decreased by co-treatment by DAPT (P<0.05). Hyperoxia also resulted in enhanced NG2 expression and lowered MBP expression in the brain (P<0.05). Compared with the control mice, the mice exposed to hyperoxia showed prolonged escape latency (P<0.05) and spent less time in the target quadrant with a lowered number of passing through the virtual platform (P<0.05). All these parameters were significantly improved by co-treatment with DAPT.</p><p><b>CONCLUSION</b>Specific inhibition of Notch signaling pathway activation in the brain by the γ-secretase inhibitor DAPT can ameliorate white matter injury and learning and memory impairment in newborn mice with hyperoxia exposure.</p>

Monitoring Nonsurgical and Surgical Root Canal Treatment of Teeth with Primary and Secondary Infections

The aim of this study was to monitor nonsurgical and surgical root canal treatment (RCT) of teeth with primary and secondary infections and apical periodontitis (AP). This prospective clinical study comprised the treatment of 80 patients with primary and persistent secondary infections and AP. Of this initial sample, forty patients did not return. Periapical index using cone beam computed tomography scans (CBCTPAI) was used to aid diagnosis, planning and to determine the better therapeutic strategy. Twenty patients (26 teeth) diagnosed with primary infection and AP received conventional RCT and were followed up for 10 to 36 months. Twenty patients (31 teeth) diagnosed with persistent secondary infection were submitted to periapical surgical and followed up for 6 to 30 months. The results showed RCT successful in 19/26 cases with complete AP healing (5/26 with partial repair) in 10-36 months of follow up. For the surgically managed cases, effectiveness of surgical therapy was detected in 10/31 cases with complete healing (10/31 cases with partial repair) within 6-30 months follow up. The return of patients for clinical and radiographic follow-up, and obedience to the proposed time period was very short from ideal. The levels of success in both therapeutic protocols were high. RCT failures were detected even with rigorous standard clinical protocols.

O objetivo do estudo foi monitorar tratamentos de canais radiculares (TCR) convencionais e com auxílio de cirurgia periapical. Este estudo prospectivo constituiu de 80 pacientes portadores de infecções primárias e secundárias persistentes e periodontite apical (PA). O índice periapical utilizando tomografia computadorizada de feixe cônico (CBCTPAI) foi utilizado como auxiliar no diagnóstico, planejamento e para determinar a melhor estratégia terapêutica. Apenas 40 pacientes retornaram para o TCR. Em 20 pacientes (26 dentes) com diagnósticos de infecções primárias e PA foram feitos TCR convencionais e monitoramentos por 10 a 36 meses. Em 20 pacientes (31 dentes) com diagnósticos de infecções secundárias persistentes foram submetidos a procedimentos cirúrgicos e acompanhamentos durante 6 a 30 meses. Os resultados mostraram TCR bem sucedidos em 19 de 26 casos, com curas completas das PA (5 de 26 com reparação parcial) em controles de 10 a 36 meses. Para os casos de tratamentos cirúrgicos foram detectadas eficácias das terapêuticas cirúrgicas em 10 de 31 casos com curas completas (10 de 31 casos com reparação parcial) em controles de 6 a 30 meses. O retorno dos pacientes para controle clínico e radiográfico e a obediência ao período de tempo proposto está muito aquém do ideal. Os níveis de sucesso em ambos os protocolos terapêuticos se mostraram elevados. Fracassos no TCR foram detectados mesmo utilizando protocolo clínico com rigoroso padrão.

Entre o campo e o laboratório: a dinâmica de produção de conhecimento no Ambulatório de Menopausa do Caism/Unicamp / Between the country and the laboratory: the dynamics of the production of knowledge at the Menopause Outpatients Clinic at Caism, Unicamp

Este estudo investiga as práticas de produção de conhecimento sobre a menopausa no Caism/Unicamp, centro de referência para políticas públicas em saúde da mulher. Foram realizadas observações de consultas ginecológicas, entrevistas com mulheres e médicos e observação de reuniões de apoio psicológico, buscando identificar os discursos que circulam no lugar e o processo de alistamento de diferentes atores para que os conhecimentos ali produzidos alcancem credibilidade e “viajem” além dos limites do hospital-escola, tornando-se “universais”. A análise baseia-se nos “estudos localistas”, alinhados aos estudos sociais de ciência e tecnologia.

This study investigates the practices involved in the production of knowledge about menopause at Caism, Unicamp, a reference center for public policies for women’s health. Gynecological appointments and psychological support meetings were observed, and women and doctors were interviewed in order to identify what discourse circulates there and how different actors are brought in to ensure that the knowledge produced attains credibility and “travels” beyond the boundaries of the teaching hospital to become “universal”. The analysis is based on localized studies aligned with social studies of science and technology.

Adenosina trifosfato bioluminescência para avaliação da limpeza de superfícies: uma revisão integrativa / Adenosine triphosphate bioluminescence to evaluate the effectiveness of surface cleaning: an integrative review / Bioluminiscencia adenosina trifosfato para evaluar la eficacia de la limpieza de superficies: una revisión integrativa

Objetivo: Identificar na literatura indicações e controvérsias do ATP bioluminescência para avaliação da efetividade da limpeza de superfícies em estabelecimentos de saúde. Método: Revisão integrativa da literatura, entre 2000 e 2012, nas bases de dados MEDLINE, LILACS, Science Direct, SCOPUS e Isi Web of Knowledge. Resultados: Selecionou-se para esta revisão 15 artigos. O ATP bioluminescência foi apontado como importante recurso educacional e método complementar à inspeção visual e às análises microbiológicas na avaliação da efetividade da limpeza. A impossibilidade de indicar a contaminação da superfície por micro-organismos viáveis, a interferência por substâncias químicas e a dificuldade de interpretação dos resultados constituem as principais controvérsias para o uso deste nos serviços de saúde. Conclusão: Apesar de constituir importante recurso na avaliação da limpeza de superfícies, mais estudos são necessários para incorporação efetiva do método nos serviços de saúde. .

Objective: To identify indications and controversies in the literature of the use of ATP bioluminescence to evaluate the effectiveness of surface cleaning in healthcare facilities. Method: Integrative literature review between 2000 and 2012 in the following databases: MEDLINE, LILACS, Science Direct, SCOPUS and Isi Web of Knowledge. Results: were selected for this review 15 articles. The ATP bioluminescence was considered an important educational resource and complementary method to visual inspection and microbiological evaluation of the effectiveness of cleaning. The impossibility to indicate surface contamination by microorganisms, interference by chemicals and the difficulty of interpreting the results constitute the main controversies in the use of ATP in health services. Conclusion: Although this is an important resource in the evaluation of surface cleaning, more studies are necessary for effective incorporation of the method in health services. .

Objetivo: Identificar en la literatura las indicaciones y controversias sobre el uso de la bioluminiscencia ATP para evaluar la eficacia de la limpieza de superficies en los servicios de salud. Método: Revisión integrativa de la literatura, entre 2000 y 2012, en las siguientes bases de datos: MEDLINE, LILACS, Science Direct, SCOPUS e ISI Web of Knowledge. Resultados: Se seleccionaron para esta revisión 15 artículos. La bioluminiscencia del ATP se considera un importante recurso educativo y método complementario a la inspección visual y la análisis microbiológica de la evaluación de la efectividad de la limpieza. La imposibilidad de indicar contaminación de la superficie por los microorganismos, la interferencia por los productos químicos y la dificultad de interpretar los resultados constituyen las principales controversias en la utilización de ATP en los servicios de salud. Conclusión: Aunque esto es un elemento importante en la evaluación de limpieza de superficies, se necesitan más estudios para incorporación eficaz del método en los servicios de salud. .

Some current challenges in research on air pollution and health / Desafíos actuales de la investigación sobre contaminación del aire y salud

This commentary addresses some of the diverse questions of current interest with regard to the health effects of air pollution, including exposure-response relationships, toxicity of inhaled particles and risks to health, multipollutant mixtures, traffic-related pollution, accountability research, and issues with susceptibility and vulnerability. It considers the challenges posed to researchers as they attempt to provide useful evidence for policy-makers relevant to these issues. This commentary accompanies papers giving the results from the ESCALA project, a multi-city study in Latin America that has an overall goal of providing policy-relevant results. While progress has been made in improving air quality, driven by epidemiological evidence that air pollution is adversely affecting public health, the research questions have become more subtle and challenging as levels of air pollution dropped. More research is still needed, but also novel methods and approaches to address these new questions.

Este comentario aborda algunos de los temas de interés actual en relación con los efectos de la contaminación del aire sobre la salud, tales como las relaciones exposición-respuesta, la toxicidad y riesgos para la salud de las partículas inhaladas, las mezclas de contaminantes múltiples, la contaminación relacionada con el tráfico, la investigación sobre responsabilidad, y los problemas de susceptibilidad y vulnerabilidad. Considera los retos que se presentan a los investigadores que intentan proporcionar evidencia para los responsables políticos en estas cuestiones. Este texto acompaña otros trabajos con resultados del proyecto ESCALA, un estudio en varias ciudades de América Latina que tiene como objetivo general proporcionar resultados relevantes para la política pública. Aunque ha habido avances para mejorar la calidad del aire, gracias a la evidencia epidemiológica de que la contaminación aérea está afectando negativamente a la salud pública, las preguntas de investigación se han vuelto más sutiles y difíciles a medida que los niveles de contaminación se reducen. Se necesita más investigación, pero también nuevos métodos y enfoques capaces de enfrentar estas preguntas.

Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice / 中国天然药物

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.

Buspirone along with melatonin attenuates oxidative damage and anxiety-like behavior in a mouse model of immobilization stress / 中国天然药物

AIM@#Stress is recognized to precipitate anxiety and related psychological problems characterized by a wide range of biochemical and behavioral changes. The present study was carried out to investigate the protective effects of melatonin and buspirone, and their combination, against six hours immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice.@*METHOD@#Male Laca mice were pre-treated with melatonin (2.5, 5 mg·kg(-1)), buspirone (5, 10 mg·kg(-1)), and their combination for consecutive five days. On the 6(th) day, animals were immobilized for six hours, and thereafter various behavioral tests were performed followed by biochemical tests.@*RESULTS@#Immobilization stress significantly impaired body weight, locomotor activity, and caused anxiety-like behavior, along with increased oxidative damage. Pretreatment with melatonin and buspirone significantly improved the loss in body weight and locomotor activity, attenuated anxiety-like behavior (in both the mirror chamber and plus maze performance tasks), further restored the levels of brain total proteins, and caused antioxidant-like effects, as evidenced by reduced lipid peroxidation, nitrite concentration, and restoration of reduced glutathione and catalase activity, as compared to control animals. In addition, combination of melatonin (2.5, 5 mg·kg(-1)) with buspirone (5 mg·kg(-1)) significantly potentiated their protective effects, as compared to their effects individually.@*CONCLUSION@#The present study suggests that melatonin potentiates the beneficial effect of buspirone against immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice possibly by involving a serotonergic mechanism.

Effects of sildenafil citrate on mice hearing / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>The purpose of this investigation was to study the effects of the Sildenafil citrate on mice hearing.</p><p><b>METHODS</b>Seven-week-old adult male Kunming mice were used. The mice were randomly divided into four groups with 10 mice in each group.Sildenafil groups were orally administered daily with sildenafil [0.1 mg/(kg·d), 1 mg/(kg·d), 10 mg/(kg·d)] and control group was orally administered with normal saline. Then mice were tested for auditory brainstem response (ABR) to observe the changes of ABR's thresholds at before administration and 1, 5, 10, 15, 20 day afterwards. The mice basilar membrane samples were studied by immunofluorescent labeling.High performance liquid chromatography was used for determination the concentration of sildenafil in endolymph of mice cochlea. Statistical analysis was performed using SPSS 13.0.</p><p><b>RESULTS</b>After 30 min following administration, the Sildenafil in endolymph of mice cochlear could be assayed by high performance liquid chromatography, and it was dose-related.Sildenafil increased the hearing thresholds with the time of administration. Hearing thresholds increased significantly in the sildenafil group at 20 d compared to the control group (P < 0.05). After administered high dose of Sildenafil, on the 20th day, the ABR thresholds average threshold was (60.0 ± 10.0) dBnHL, and the control group was (14.5 ± 6.0) dBnHL.Hair cells damages in the base ring of cochlea could be observed in experimental group in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Sildenafil can pass through blood-labyrinth barrier to the inner ear, and doses of sildenafil administration can induce hearing impairment in mice.</p>

Protective effect of baicalin solid dispersion on D-galactosamine induced acute hepatic injury in mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the protective effect of baicalin solid dispersion (BSD) on D-galactosamine (D-GalN) induced acute hepatic injury in mice, and to compare it with baicalin alone.</p><p><b>METHODS</b>Sixty mice were randomly divided into six groups, i.e., the normal control group, the D-GalN model group, the bifendate group (at the daily dose of 200 mg/kg), the baicalin group (at the daily dose of 50 mg/kg), the low dose BSD group (at the daily dose of 50 mg/kg), and the high dose BSD group (at the daily dose of 100 mg/kg), 10 in each group. 0.5% CMC-Na at 20 mL/kg was administered to mice in the normal group and the model group by gastrogavage, while corresponding medication was administered to mice in the other three groups by gastrogavage. Seven days after administration, acute hepatic injury model was induced by intraperitoneal injection of D-GalN. The liver index and the spleen index were calculated. The serum activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST), the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the liver homogenate were measured. The pathological changes of the liver tissue were observed by HE staining.</p><p><b>RESULTS</b>Compared with the normal control group, widespread inflammation and necrosis was significant in the liver tissue of the D-GalN model group; the liver index, serum ALT and AST levels and hepatic MDA content obviously increased, hepatic SOD activity decreased, showing statistical difference (P < 0.05). Compared with the model group, the liver index, the serum levels of ALT and AST, and hepatic MDA decreased, hepatic SOD increased, the degree of hepatic tissue injury was significantly improved in the low dose and high dose BSD groups. Besides, better effects were obtained in the low dose BSD group than in the baicalin group with statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>BSD could significantly protect D-GalN induced acute hepatic injury of mice, and its effect was superior to that of baicalin alone.</p>

Effect of Fuzhenghuayu compound on hepatocyte expression of Nrf2 in a mouse model of hepatic fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Fuzhenghuayu compound (FZHc) on expression of nuclear factor E2-related factor 2 (Nrf2) in hepatocytes under conditions of hepatic fibrosis using a mouse model.</p><p><b>METHODS</b>Mice were randomly assigned to a control group and a hepatic fibrosis model group. The control group was further divided into three subgroups for use as normal controls (A1), mineral oil-treated controls (A2), and FZHc-treated controls (A3); the hepatic fibrosis model group was administered carbon tetrachloride (CC14 dissolved in mineral oil and injected intraperitoneally) and further divided into four subgroups for use as 6-weeks models (B1), 10-weeks models (B2), low-dose (L)-FZHc models (C1), and high-dose (H)-FZHc models (C2). The FZHc (capsule powder diluted with double-distilled water to 0.1 g/mL) was administered via gastric perfusion to groups A3, C1, and C2 starting at week 7 of the experiment. At the end of week 6 and 10, hepatic specimens were collected and evaluated for degree of hepatic fibrosis and inflammation using routine haematoxylin-eosin staining and Masson staining. Immunohistochemical analysis was performed to measure the hepatocyte expression of Nrf2, NAD(P)H quinine oxidoreductase 1 (Nqol), a-smooth muscle actin (a-SMA) and fibronectin (FN). Real-time fluorescence quantitative PCR was used to measure Nrf2 mRNA expression. Western blotting was used to detect Nrf2 and Nqol total protein expression and Nrf2 nuclear translocation. F test, LSD test and ridit test were used for statistical analyses.</p><p><b>RESULTS</b>Compared with the B2 group (ridit value: 0.09), the model groups treated with FZHc showed significantly lower degrees of hepatic inflammation and fibrosis for both the low (C1 group, ridit value: 0.32) and high doses (C2 group, ridit value: 0.40) (F =82.927, P less than 0.05). In addition, compared with the B2 group, the model groups treated with FZHc showed significantly decreased expression of a-SMA and FN proteins, with a dose-dependent trend (by immunohistochemistry: C 1 group at the end of 10 weeks, F =77.421, 118.262, P less than 0.05; C2 group, P =0.002, 0.013) and significantly increased expression of Nrf2 and Nqol proteins (by immunohistochemistry:C1 and C2 groups at the end of 10 weeks, F =182.537, 75.615, P less than 0.05 and by westen blotting: F =45.664, 127.673, P less than 0.05), which also showed a dose-dependent trend (C2 group, P =0.000, 0.014; 0.005, 0.014). Western blotting also indicated that the amount of nuclear transported Nrf2 was higher in the C1 and C2 groups at the end of 10 weeks (vs. B2 group, F =94.787, P less than 0.05), and the amount of nuclear transported Nrf2 was significantly higher in the C2 group (vs. C1 group, P =0.044). Nrf2 mRNA expression was significantly higher in the C1 group than in the B2 group (F =3230.105, P less than 0.05), and the C2 group had more substantially increased expression (P =0.001); there was no statistical difference found between groups B1 and B2 (P =0.094).</p><p><b>CONCLUSION</b>Fuzhenghuayu compound increased the expression of Nrf2 mRNA and protein under conditions of hepatic fibrosis in mice and stimulated Nrf2 nuclear transport, as well as increased expression of the Nrf2 target gene Nqol that is known to suppress activation of hepatic stellate cells and decrease the deposition of FN. Therefore, Fuzhenghuayu compound may ameliorate hepatocyte injury in hepatic fibrosis in mice by exerting an antihepatic fibrosis effect.</p>

Protective effects of antioxidants on chronic intermittent hypoxia-induced cardiac remodeling in mice / 中华心血管病杂志

<p><b>OBJECTIVE</b>Chronic intermittent hypoxia (CIH) animal model was used to mimic the status of obstructive sleep apnea (OSA) in order to investigate the pathological mechanism of CIH-induced cardiac remodeling and observe the protective effect of antioxidants.</p><p><b>METHODS</b>FVB mice (8-10 weeks-old) were randomly divided into control (saline, i.p.) group and CIH group, reduced form of nicotinamide adenine dinucleotide phosphate oxidase inhibitor, apocynin (APO, 3 mg×kg(-1)×d(-1), i.p.) alone or CIH+APO, SOD mimic MnTMPyP (SODM, 5 mg×kg(-1)×d(-1), i.p.) alone or CIH+SODM (n = 5 each). After 4 weeks, cardiac function and structure were determined by echocardiography, cardiac inflammation, apoptosis, cardiac fibrosis and cardiac MDA contents were examined by Western blot and chemical-biological methods, respectively.</p><p><b>RESULTS</b>(1) Heart weight, LVIDd and LVIDs were increased while LVEF and FS were reduced in CIH group compared to control group (all P < 0.05). (2) Myocardial protein expression of ANP and VCAM-1 was significantly upregulated, myocardial MDA content and apoptosis as well as myocardial fibrosis marker CTGF and PAI-1 were increased in CIH group compared to control group (all P < 0.05). (3) Above parameters were similar between APO and CIH+APO as well as SODM and CIH+SODM (all P > 0.05).</p><p><b>CONCLUSION</b>CIH could induce cardiac remodeling and CIH-induced cardiac inflammation, cardiac oxidative injury, cardiac apoptosis and cardiac fibrosis serve as the pathological mechanisms of CIH-induced cardiac remodeling. The protective effects of the two antioxidants suggest that the main mechanism of CIH-induced cardiac injury is oxidative stress.</p>

Effect of jujube on the expression of CYP2E1 and TNF-alpha in the hepatic tissue of mice with alcoholic liver disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of jujube pretreatment on serum levels of AST and ALT, liver pathology, and the expression of cytochrome P4502e1 (CYP2E1) and tumor necrosis factor-alpha (TNF-alpha) in the liver tissue of alcoholic liver disease (ALD) mice.</p><p><b>METHODS</b>Totally 88 Kunming mice were randomly divided into the control group (n = 28), the model group (n = 32), and the jujube treatment group (n = 28). The animal model was prepared using intragastric alcoholism for mice in the model group and the jujube treatment group, while distilled water was intragastrically given to those in the control group. Extraction of jujube was intragastrically given to mice in the jujube treatment group at week 4, while equal volume of distilled water was intragastrically given to mice in the rest two groups. The therapeutic course lasted for 12 weeks. Serum levels of AST and ALT, liver pathology, and the expression of CYP2E1 and TNF-alpha in the liver tissue of ALD mice were observed after administration of jujube.</p><p><b>RESULTS</b>Compared with the model group, serum levels of AST and ALT decreased, the liver pathology was improved, and the expression of CYP2E1 and TNF-alpha in the liver tissue decreased, showing statistical difference (P < 0.05).</p><p><b>CONCLUSION</b>Jujube had certain effect in treating ALD.</p>