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Braz. j. biol ; 84: e253061, 2024. tab, graf
Article in English | LILACS-Express | MEDLINE, LILACSEXPRESS, LILACS, VETINDEX | ID: biblio-1364520


Abstract Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

Resumo A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Journal of Clinical Hepatology ; (12): 392-396, 2022.
Article in Chinese | WPRIM | ID: wpr-920890


Objective To investigate the effect of the mitochondria-targeted antioxidant SS-31 on acute liver injury in a mouse model of sepsis. Methods A total of 24 adult male C57BL/6J mice were randomly divided into control group, control+SS-31 group, lipopolysaccharide (LPS) group, and LPS+SS-31 group, with 6 mice in each group. The mice were given intraperitoneal injection of LPS (10 mg/kg) to establish a model of sepsis and acute liver injury, followed by intraperitoneal injection of SS-31 (10 mg/kg) for treatment, and the mice in the control group were given intraperitoneal injection of an equal volume of PBS solution, followed by intraperitoneal injection of an equal volume of normal saline. After 12 hours, ELISA was used to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), superoxide dismutase (SOD), tumor necrosis factor-α (TNFα), interleukin-1β(IL-1β), and interleukin-6 (IL-6), and HE staining was used to observe liver histopathological changes. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the LPS group, the LPS+SS-31 group had significant reductions in the serum levels of ALT (140.05±12.22 U/L vs 102.64±8.75 U/L, P < 0.05) and AST (80.22±4.71 U/L vs 69.26±5.37 U/L, P < 0.05) and the levels of ROS (1 030.21±115.87 pg/mL vs 847.84±63.65 pg/mL, P < 0.05), TNFα (767.18±60.60 ng/mL vs 698.89±16.99 ng/mL, P < 0.05), IL-1β (29.97±1.37 ng/mL vs 26.70±3.09 ng/mL, P < 0.05), and IL-6 (59.13±7.09 pg/mL vs 49.29±3.41 pg/mL, P < 0.05) in liver tissue. Compared with the control group based on HE staining, the LPS group showed destruction of hepatic lobular structure, inflammatory cell infiltration, ambiguous intercellular space, and hepatocyte swelling, while the LPS+SS-31 group showed alleviation of inflammatory cell infiltration and hepatocyte swelling. Conclusion The mitochondria-targeted antioxidant SS-31 can reduce the production of ROS, downregulate the highly expressed inflammatory factors in sepsis, and alleviate sepsis-related acute liver injury in mice.

Article in Chinese | WPRIM | ID: wpr-920744


Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of alveolar echinococcosis using high-resolution mass spectrometry with data independent acquisition (DIA), and to identify the key proteins contributing to the pathogenesis of alveolar echinococcosis. Methods Protoscoleces were isolated from Microtus fuscus with alveolar echinococcosis and the experimental model of alveolar echinococcosis was established in female Kunming mice aged 6 to 8 weeks by infection with Echinococcus multilocularis protoscoleces. Mice were divided into the experimental and control groups, and animals in the experimental group was injected with approximately 3 000 protoscoleces, while mice in the control group were injected with the same volume of physiological saline. Mouse liver specimens were sampled from both groups one year post-infection and subjected to pathological examinations. In addition, the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the experimental group and the normal liver specimens (the normal group) were sampled from mice in the control group for DIA proteomics analysis, and the differentially expressed proteins were subjected to bioinformatics analysis. Results A total of 1 020 differentially expressed proteins were identified between the lesion group and the normal group, including 671 up-regulated proteins and 349 down-regulated proteins, and 495 differentially expressed proteins were identified between the peri-lesion group and the normal group, including 327 up-regulated proteins and 168 down-regulated proteins. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these differentially expressed proteins were involved in peroxisome, peroxisome proliferator-activated receptor (PPAR) and fatty acid degradation pathways, and the peroxisome and PPAR signaling pathways were found to correlate with liver injury. Several differentially expressed proteins that may contribute to the pathogenesis of alveolar echinococcosis were identified in these two pathways, including fatty acid binding protein 1 (Fabp1), Acyl-CoA synthetase long chain family member 1 (Acsl1), Acyl-CoA oxidase 1 (Acox1), Enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) and Acetyl-Coenzyme A acyltransferase 1B (Acaa1b), which were down-regulated in mice in the experimental group. Conclusion A large number of differentially expressed proteins are identified in the liver of the mouse model of alveolar echinococcosis, and Fabp1, Acsl1, Acox1, Ehhadh and Acaa1b may contribute to the pathogenesis of alveolar echinococcosis.

Article in Chinese | WPRIM | ID: wpr-920743


Objective To identify the differentially expressed proteins in different liver tissues in the mouse model of cystic echinococcosis (CE), so as to provide insights into the research and development of therapeutic drugs targeting CE. Methods Female Kunming mice at ages of 6 to 8 weeks were randomly assigned into the CE group and the control group. Mice in the CE group were intraperitoneally infected with 2 000 Echinococcus multilocularis protoscoleces, while mice in the control group were injected with the same volume of physiological saline. All mice in both groups were sacrificed after breeding for 350 d, and the lesions (the lesion group) and peri-lesion specimens (the peri-lesion group) were sampled from the liver of mice in the CE group and the normal liver specimens (the normal group) were sampled from mice in the control group for data independent acquisition (DIA) proteomics analysis, and the differentially expressed proteins were subjected to Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results A total of 26 differentially expressed proteins were identified between the lesion group and the normal group and between the peri-lesion group and the normal group, including 8 up-regulated proteins and 18 down-regulated proteins. GO term enrichment analysis showed that these differentially expressed proteins were predominantly enriched in endoplasmic reticulum membrane (biological components), oxidoreductase activity (molecular function) and oxoacid metabolic process and monocarboxylic acid metabolic process (biological processes). KEGG pathway enrichment analysis revealed that the differentially expressed protein Acyl-CoA oxidase 1 (Acox1), which contributed to primary bile acid biosynthesis during the fatty acid oxidation, was involved in peroxisome signaling pathway, and the differentially expressed protein fatty acid binding protein 1 (Fabp1), which contributed to fatty acid transport, was involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Conclusion Differentially expressed proteins are identified in the liver specimens between mouse models of CE and normal mice, and some differentially expressed proteins may serve as potential drug targets for CE.

Acta cir. bras ; 37(1): e370105, 2022. tab, graf
Article in English | LILACS-Express | MEDLINE, LILACSEXPRESS, LILACS, VETINDEX | ID: biblio-1364250


ABSTRACT Purpose: To evaluate how the induction of liver damage by ischemia and reperfusion affects the adipose tissue of lean and obese mice. Methods: Lean and diet-induced obese mice were subjected to liver ischemia (30 min) followed by 6 h of reperfusion. The vascular stromal fraction of visceral adipose tissue was analyzed by cytometry, and gene expression was evaluated by an Array assay and by RT-qPCR. Intestinal permeability was assessed by oral administration of fluorescein isothiocyanate (FITC)-dextran and endotoxemia by serum endotoxin measurements using a limulus amebocyte lysate assay. Results: It was found that, after liver ischemia and reperfusion, there is an infiltration of neutrophils, monocytes, and lymphocytes, as well as an increase in the gene expression that encode cytokines, chemokines and their receptors in the visceral adipose tissue of lean mice. This inflammatory response was associated with the presence of endotoxemia in lean mice. However, these changes were not observed in the visceral adipose tissue of obese mice. Conclusions: Liver ischemia and reperfusion induce an acute inflammatory response in adipose tissue of lean mice characterized by an intense chemokine induction and leukocyte infiltration; however, inflammatory alterations are already present at baseline in the obese adipose tissue and liver ischemia and reperfusion do not injure further.

Braz. j. med. biol. res ; 55: e11735, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1355914


Oral tolerance blocks the development of specific immune responses to proteins ingested by the oral route. One of the first registries of oral tolerance showed that guinea pigs fed corn became refractory to hypersensitivity to corn proteins. Mice fed with chow containing corn are tolerant to zein, and parenteral injection of zein plus adjuvant blocks immunization to unrelated proteins injected concomitantly and reduces unspecific inflammation. Extensive and prolonged inflammatory infiltrate in the wound bed is one of the causes of pathological wound healing. Previous research shows that intraperitoneal injection of zein concomitant with skin injuries reduces the inflammatory infiltrate in the wound bed and improves wound healing. Herein, we tested if one subcutaneous injection of zein before skin injury improves wound healing. We also investigated how long the effects triggered by zein could improve skin wound healing. Mice fed zein received two excisional wounds on the interscapular skin under anesthesia. Zein plus Al(OH)3 was injected at the tail base at 10 min, or 3, 5, or 7 days before skin injuries. Wound healing was analyzed at days 7 and 40 after injury. Our results showed that a zein injection up to 5 days before skin injury reduced the inflammatory infiltrate, increased the number of T-cells in the wound bed, and improved the pattern of collagen deposition in the neodermis. These findings could promote the development of new strategies for the treatment and prevention of pathological healing using proteins normally found in the common diet.

Article in English | LILACS-Express | LILACS | ID: biblio-1360788


ABSTRACT The Western-blotting technique was applied to identify antigenic fractions of excretory-secretory Toxocara canis antigen recognized by IgG antibodies throughout an experimental infection in mice challenged by different inocula. Mice were inoculated with 5, 50 and 500 embryonated eggs and serum samples were collected 15, 30, 60, 90 and 120 days post-infection. Serum samples were analyzed using an excretory-secretory Toxocara antigen. Antibodies recognized antigenic fractions from 30 to 90 kDa. The protein fraction of 30-35 kDa was the most frequently recognized regardless of the size of inoculum and the stage of infection represented by the different collection times, but the antigenic recognition was more evident in groups infected with 50 and 500 eggs. This study presents an antigenic panel of the excretory-secretory antigen of T. canis and suggests that the 30-35 kDa antigenic fraction is a promising marker of the infection and should be further explored in future studies on experimental toxocariasis.

Braz. arch. biol. technol ; 65: e22200620, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364468


Abstract: Asthma is a chronic respiratory disease affecting 300 million people worldwide. It results in several structural changes in the airways, which are minimally accessible in clinical practice. Cell therapy using mesenchymal stromal cells (MSCs) is a promising strategy for treating asthma due to the paracrine activity of MSCs, which influences tissue regeneration and modulates the immune response. Studies using extracellular vesicles (EV) released by MSCs have demonstrated their regenerative properties in animal models. The aim of this study was to evaluate the potential of EVs isolated from human bone marrow MSCs (hBM-MSCs) to control lung tissue remodeling in ovalbumin-induced allergic asthma in Balb/c mice. We isolated hBM-MSCs from a single donor, expanded and characterized them, and then isolated EVs. Asthma was induced in 43 male Balb/c mice, divided into four groups: control, asthmatic (AS), asthmatic plus systemic EVs (EV-S), and asthmatic plus intratracheal EVs (EV-IT). Upon completion of asthma induction, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S). Seven days after, we performed bronchoalveolar lavage (BAL) and the total nuclear cells were counted. The animals were euthanized, and the lungs were collected for histopathological analysis of the airways. The EV-S group showed improvement in only the total BAL cell count compared with the AS group, while the EV-IT group showed significant improvement in almost all evaluated criteria. Therefore, we demonstrate that the local application of EVs derived from hBM-MSCs may be a potential treatment in controlling asthma.

Braz. j. med. biol. res ; 55: e11774, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364555


Elastase-2 (ELA-2) is an angiotensin II-generating enzyme that participates in the cardiovascular system. ELA-2 is involved in hemodynamic and autonomic control and is upregulated in myocardial infarction and hypertension. The inhibition of angiotensin-converting enzyme (ACE) increased ELA-2 expression in the carotid arteries and heart of spontaneously hypertensive rats. In this study, we sought to investigate the role of ACE inhibition in hemodynamic and autonomic balance in elastase-2 knockout (ELA-2 KO) mice. Male ELA-2 KO and C57BL/6 mice were treated with the ACE inhibitor enalapril or saline for 10 days. After treatment, mice underwent surgery for cannulation of the femoral artery and arterial pressure recordings were made five days later in awake animals. The variability of systolic blood pressure (SBP) and pulse interval (PI) was evaluated in the time and frequency domain. Spontaneous baroreflex was assessed by the sequencing method. ACE inhibition caused a significant decrease in mean arterial pressure (117±2.2 vs 100±2.8 mmHg) and an increase in heart rate (570±32 vs 655±15 bpm) in ELA-2 KO mice. Despite a tendency towards reduction in the overall heart rate variability (standard deviation of successive values: 7.6±1.1 vs 4.7±0.6 ms, P=0.08), no changes were found in the root of the mean sum of squares or in the power of the high-frequency band. ACE inhibition did not change the spontaneous baroreflex indices (gain and baroreflex effectiveness index) in ELA-2 KO mice. Altogether, this data suggested that ACE played a role in the maintenance of hemodynamic function in ELA-2 KO mice.

Braz. J. Pharm. Sci. (Online) ; 58: e18524, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364432


Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali

Animals , Male , Female , Mice , Stomach/drug effects , Stomach Ulcer/pathology , Tissues/drug effects , Tissue Distribution , Astragalus Plant/adverse effects , Plants, Medicinal , Administration, Oral
Protein & Cell ; (12): 102-119, 2022.
Article in English | WPRIM | ID: wpr-922497


The use of two inhibitors of Mek1/2 and Gsk3β (2i) promotes the generation of mouse diploid and haploid embryonic stem cells (ESCs) from the inner cell mass of biparental and uniparental blastocysts, respectively. However, a system enabling long-term maintenance of imprints in ESCs has proven challenging. Here, we report that the use of a two-step a2i (alternative two inhibitors of Src and Gsk3β, TSa2i) derivation/culture protocol results in the establishment of androgenetic haploid ESCs (AG-haESCs) with stable DNA methylation at paternal DMRs (differentially DNA methylated regions) up to passage 60 that can efficiently support generating mice upon oocyte injection. We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations. Furthermore, we demonstrate that TSa2i-treated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation. Strikingly, AG-haESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells, in part through the enhanced proliferation of H19-DMR hypermethylated cells. Together, we establish AG-haESCs that can long-term maintain paternal imprints.

Article in English | WPRIM | ID: wpr-906678


@#BACKGROUND: To investigate effects of Maxingloushi decoction on lung inflammation and programmed death markers (programmed death-1 [PD-1], programmed death-ligand 1 [PD-L1]) in the lung tissue, peripheral blood, and bronchoalveolar lavage fluid (BLF) in a mouse model of chronic obstructive pulmonary disease (COPD). METHODS: Thirty-six mature male BALB/C mice were randomly divided into normal group (group A, n=6), COPD model group (group B, n=10), Maxingloushi decoction + COPD group (group C, n=10), and PD-1 inhibitor + COPD group (group D, n=10). The COPD model was established by smoke inhalation combined with lipopolysaccharide (LPS). Levels of PD-1 and PD-L1 in plasma and BLF were measured by enzyme-linked immunosorbent assay (ELISA). Histopathological techniques were used to semi-quantitatively analyze the immuno-fluorescence optical density (IOD) value of the lung tissue. RESULTS: In plasma and BLF, the expression of PD-1 in the group B was higher than that in the group A, and the expression of PD-L1 was lower than that in the group A. The expression of PD-1 and PD-L1 in the lung tissue was normalized in the group C in comparison with the group B (P<0.05) and the group D (P<0.05), and inflammatory cell infiltration in the lung tissue was also improved. CONCLUSIONS: These findings reveal that COPD causes an immune imbalance in the peripheral blood and lung tissue, and that both Maxingloushi decoction and PD-1 inhibitor treatment can mitigate lung inflammation in COPD by reducing PD-1 expression and increasing PD-L1 expression. The treatment effect of Maxingloushi decoction may be superior to that of PD-1 inhibitor.

Biomédica (Bogotá) ; 41(4): 706-720, oct.-dic. 2021. tab, graf
Article in English | LILACS | ID: biblio-1355744


Abstract | Introduction: Broccoli (Brassica oleracea) is well known for its properties as an anticancer, antioxidant, and scavenger of free radicals. However, its benefits in enhancing spermatogenesis have not been well established. Objective: To study broccoli aqueous extract effects on sperm factors and the expression of genes Catsper1, Catsper2, Arl4a, Sox5, and Sox9 in sperm factors in mice. Materials and methods: Male mice were divided randomly into six groups: (1) Control; (2) cadmium (3 mg/kg of mouse body weight); (3) orally treated with 200 µl broccoli aqueous extract (1 g ml-1); (4) orally treated with 400 µl of broccoli aqueous extract; (5) orally treated with 200 broccoli aqueous extract plus cadmium, and (6) orally treated with 400 µl of broccoli aqueous extract plus cadmium. We analyzed the sperms factors and Catsper1, Catsper2, Arl4a, Sox5, and Sox9 gene expression. Results: An obvious improvement in sperm count and a slight enhancement in sperm motility were observed in mice treated with broccoli extract alone or with cadmium. Sperm viability was reduced by broccoli extract except for the 200 µl dose with cadmium, which significantly increased it. Interestingly, Arl4a gene expression increased in the 400 µl broccoli- treated group. Likewise, the Arl4a mRNA level in mice treated with cadmium and 200 µl of broccoli extract was higher than in the cadmium-treated mice. Furthermore, broccoli extract enhanced the mRNA level of Catsper2 and Sox5 genes in mice treated with 200 µl and 400 µl broccoli extract plus cadmium compared with the group treated solely with cadmium. Conclusion: The higher sperm count in broccoli-treated mice opens the way for the development of pharmaceutical products for infertile men.

Resumen | Introducción. El brócoli (Brassica oleracea) se conoce por sus propiedades como anticancerígeno, antioxidante y eliminador de radicales libres. Sin embargo, sus beneficios en la espermatogénesis aún no se han determinado suficientemente. Objetivo. Estudiar los efectos del extracto acuoso de brócoli sobre los factores espermáticos y la expresión de los genes Catsper1, Catsper2, Arl4a, Sox5 y Sox9 en ratones. Materiales y métodos. Los ratones machos se dividieron aleatoriamente en seis grupos: 1) control; 2) tratados con cadmio, 3 mg/kg de peso corporal; 3) tratados con 200 µl de extracto acuoso de brócoli (1 g ml-1); 4) tratados con 400 µl de extracto acuoso de brócoli; 5) tratados con 200 µl de extracto acuoso de brócoli más cadmio, y 6) tratados con 400 µl de extracto acuoso de brócoli más cadmio. El extracto acuoso de brócoli se administró por vía oral. Se analizaron los factores espermáticos y la expresión de los genes Catsper1, Catsper2, Arl4a, Sox5 y Sox9. Resultados. Se observó una mejoría obvia en el recuento y una ligera mejoría en la motilidad de los espermatozoides, en ratones tratados con extracto de brócoli solo o con cadmio. La viabilidad de los espermatozoides se redujo con el extracto de brócoli, excepto con la dosis de 200 µl más cadmio, la cual la aumentó significativamente. Curiosamente, la expresión del gen Arl4a aumentó en el grupo tratado con 400 µl del extracto. Asimismo, el ARNm del Arl4a en ratones tratados con cadmio y 200 µl del extracto, fue más abundante que en los ratones tratados solo con cadmio. Además, el extracto de brócoli aumentó la cantidad de ARNm de los genes Catsper2 y Sox5 en ratones tratados con 200 y 400 µl de extracto de brócoli más cadmio, en comparación con el grupo tratado únicamente con cadmio. Conclusión. El mayor número de espermatozoides en ratones tratados con brócoli abre el camino al desarrollo de productos farmacéuticos para hombres infértiles.

Spermatogenesis , Brassica , Cadmium , Gene Expression , Mice
Rev. peru. med. exp. salud publica ; 38(4): 587-594, oct.-dic. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1365918


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.

Arq. bras. cardiol ; 117(4): 737-747, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345234


Resumo Fundamento A síndrome metabólica é caracterizada por um conjunto de comorbidades. Durante a síndrome, observam-se alterações estruturais no sistema cardiovascular, especialmente o remodelamento vascular. Uma das causas predisponentes para essas alterações é a inflamação crônica oriunda de mudanças na estrutura e composição do tecido adiposo perivascular. Atorvastatina é eficaz no tratamento das dislipidemias. No entanto, seus efeitos pleiotrópicos não são totalmente compreendidos. Supõe-se que, durante a síndrome metabólica, ocorre remodelamento vascular e que o tratamento com atorvastatina pode ser capaz de atenuar tal condição. Objetivos Avaliar os efeitos do tratamento com atorvastatina sobre o remodelamento vascular em modelo experimental de síndrome metabólica. Métodos Camundongos Swiss receberam dieta controle ou dieta hiperglicídica por 18 semanas. Após 14 semanas de dieta, os camundongos foram tratados com veículo ou atorvastatina (20mg/kg) durante 4 semanas. Foram avaliados o perfil nutricional e metabólico por testes bioquímicos; análise estrutural da artéria aorta por histologia e dosagem de citocinas por ensaio imunoenzimático. O nível de significância aceitável para os resultados foi p <0,05. Resultados A dieta hiperglicídica promoveu o desenvolvimento de síndrome metabólica. Tal fato culminou no remodelamento hipertrófico do músculo liso vascular e tecido adiposo perivascular. Além disso, houve aumentos das citocinas TNF-α e IL-6 circulantes e no tecido adiposo perivascular. O tratamento com atorvastatina reduziu significativamente os danos metabólicos, o remodelamento vascular e os níveis de citocinas. Conclusão Atorvastatina ameniza danos metabólicos associados à síndrome metabólica induzida por dieta hiperglicídica, além de atenuar o remodelamento vascular, sendo esses efeitos associados à redução de citocinas pró-inflamatórias.

Abstract Background Metabolic syndrome is characterized by an array of comorbidities. During this syndrome, structural changes are observed in the cardiovascular system, especially vascular remodeling. One of the predisposing causes for these changes is chronic inflammation resulting from changes in the structure and composition of perivascular adipose tissue. Atorvastatin is effective in the treatment of dyslipidemias. However, its pleiotropic effects have not been completely understood. We hypothesize that metabolic syndrome may lead to vascular remodeling and that atorvastatin therapy may be able to attenuate this condition. Objectives To assess the effects of atorvastatin therapy on vascular remodeling in an experimental model of metabolic syndrome. Methods Swiss mice received a control diet or a hyperglicemic diet for 18 weeks. After 14 weeks of diet, mice were treated with vehicle or atorvastatin (20mg/kg) during for 4 weeks. Nutritional and metabolic profiles were assessed by biochemical tests; moreover, a histological assessment of aorta structure was conducted, and cytokine levels were determined by the immunoenzyme assay. The acceptable level of significance for the results was set at p<0.05. Results Hyperglicemic diet promoted the development of metabolic syndrome. It indeed culminated in hypertrophic remodeling of vascular smooth muscle and perivascular adipose tissue. Furthermore, there were increases in the levels of circulating TNF-α and IL-6 and in the perivascular adipose tissue. Atorvastatin therapy significantly reduced metabolic damages, vascular remodeling, and cytokine levels. Conclusion Atorvastatin attenuate metabolic damages associated with metabolic syndrome induced by hyperglycemic diet, in addition to attenuating vascular remodeling; both effects are associated with reduced levels of pro-inflammatory cytokines.

Animals , Mice , Metabolic Syndrome/drug therapy , Adipose Tissue , Cytokines , Vascular Remodeling , Atorvastatin/pharmacology
Rev. peru. med. exp. salud publica ; 38(3): 424-433, jul.-sep. 2021. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1357372


RESUMEN Objetivo: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. Materiales y métodos: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40 mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. Resultados: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p = 0,037 y cerebro, p = 0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40 mg/kg y el control. Conclusiones: La DL50 para las tres chalconas fue superior a 550 mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

ABSTRACT Objective: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. Materials and methods: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. Results: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. Conclusions: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.

An. Fac. Med. (Perú) ; 82(2): 140-145, abr.-jun 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1339086


RESUMEN Objetivos. Evaluar el efecto de la harina de Myrciaria dubia (camu camu) sobre el tejido hepático inducido a toxicidad por acetaminofén en ratones. Métodos. Diseño experimental. Se preparó una suspensión de harina de camu camu (HCC) con almidón al 1,6%. Se emplearon 40 ratones machos de la cepa BALB/c, con un peso promedio de 30,8 g y de dos meses de edad, los cuales fueron divididos en cinco grupos, recibiendo el siguiente tratamiento, vía orogástrica, por un período de 10 días, grupos I y II: almidón 1,6% 10 mL/kg; grupo III: HCC 200 mg/kg, grupo IV: HCC 500 mg/kg y grupo V: HCC 800 mg/kg. Al 6to día de tratamiento se le administró acetaminofén (300 mg/kg) a los grupos II-V hasta el 10mo día. Terminada la intervención los animales fueron puestos en ayunas de 12 horas, para luego ser sacrificados previa anestesia con pentobarbital sódico. Se extrajo el hígado, se identificó y seccionó el lóbulo mayor para el estudio bioquímico e histológico. Resultados. La harina de camu camu redujo los niveles del índice hepático, y presentó un mejor perfil del sistema glutatión, comparado con el grupo II; sin embargo, las cifras de lipoperoxidación no mostraron diferencia significativa. A nivel histológico, en los grupos que recibieron HCC se observaron hepatocitos binucleados, así como un mayor mantenimiento de la polaridad; sin embargo, algunas muestras evidenciaron microvacuolas y leve fragmentación de la cromatina. Conclusión. La harina de camu camu evidenció efecto hepatoprotector frente a la toxicidad por acetaminofén en ratones.

ABSTRACT Objectives . To evaluate the effect of Myrciaria dubia (camu camu) flour on liver tissue induced to acetaminophen toxicity in mice. Methods. Experimental design. A suspension of camu camu flour (HCC) with 1.6% starch was prepared. 40 male mice of the BALB/c strain were used, with an average weight of 30.8 g and two months of age, which were divided into five groups, receiving the following treatment, orogastric route, for a period of 10 days, groups I and II: 1.6% starch 10 mL / kg; group III: HCC 200 mg / kg, group IV: HCC 500 mg / kg and group V: HCC 800 mg / kg. On the 6th day of treatment, acetaminophen (300 mg / kg) was administered to groups II-V until the 10th day. After the intervention, the animals were fasted for 12 hours, to then be sacrificed after anesthesia with sodium pentobarbital. The liver was removed, the greater lobe was identified and sectioned for biochemical and histological study. Results. The camu camu flour reduced the levels of the hepatic index, and presented a better profile of the glutathione system, compared to group II; however, the lipoperoxidation figures did not show a significant difference. At the histological level, in the groups that received HCC, binucleated hepatocytes were observed, as well as a greater maintenance of polarity; however, some samples showed microvacuoles and slight chromatin fragmentation. Conclusion. Camu camu flour showed a hepatoprotective effect against acetaminophen toxicity in mice.

Biomédica (Bogotá) ; 41(1): 99-110, ene.-mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1249062


Resumen | Introducción. El arsénico es un tóxico ambiental ampliamente diseminado en todo el mundo. En hombres y animales, diversos órganos y tejidos son blancos de sus efectos deletéreos, entre ellos, el los del sistema inmunológico. Objetivo. Determinar la intoxicación aguda por arsénico en tejidos y células diana de ratones Balb/c in vivo. Materiales y métodos. Se aplicó una inyección intraperitoneal de 9,5 o 19 mg/kg de arsenito de sodio (NaAsO2) o un volumen equivalente de solución fisiológica como control, en ratones Balb/c con 3 por cada grupo experimental. Tras media hora, los animales fueron sacrificados y se extrajeron bazos, timos, hígados, riñones y sangre. En cada muestra, se determinó la concentración de arsénico, polifenoles y hierro, y también, se evaluaron marcadores oxidativos, como peróxidos, productos avanzados de oxidación proteica y grupos sulfhidrilos libres. En los esplenocitos obtenidos del bazo, se determinaron la viabilidad celular y el potencial mitocondrial. Resultados. La dosis aguda inyectada de NaAsO2 redujo la función mitocondrial de los esplenocitos, lo que derivó en muerte celular. La presencia confirmada de arsénico en las muestras de bazo y la citotoxicidad resultante, produjeron disminución de los polifenoles y de los grupos sulfhidrilos libres, y alteraron el contenido y la distribución del hierro, pero no se aumentó la producción de peróxidos. Conclusión. Estos hallazgos aportan evidencia científica sobre los cambios en biomarcadores involucrados en la inmunotoxicidad del arsénico y ofrecen, además, una metodología para ensayar potenciales tratamientos frente a la acción deletérea de este compuesto en el sistema inmunológico.

Abstract | Introduction: Arsenic is an environmental toxic present worldwide. In men and animals, various organs and tissues are targets of its deleterious effects including those of the immune system. Objective: To determine acute arsenic toxicity in tissues and target cells of Balb/c mice using an in vivo methodology. Materials and methods: We injected Balb/c mice intraperitoneally with 9.5 or 19 mg/ kg of sodium arsenite (NaAsO2), or an equivalent volume of physiological solution as a control (with 3 per experimental group). After 30 minutes, the animals were sacrificed to obtain spleen, thymus, liver, kidneys, and blood. We determined arsenic, polyphenols, and iron concentrations in each sample and we evaluated the oxidative markers (peroxides, advanced products of protein oxidation, and free sulfhydryl groups). In splenocytes from the spleen, cell viability and mitochondrial potential were also determined. Results: The exposure to an acute dose of NaAsO2 reduced the mitochondrial function of splenocytes, which resulted in cell death. Simultaneously, the confirmed presence of arsenic in spleen samples and the resulting cytotoxicity occurred with a decrease in polyphenols, free sulfhydryl groups, and an alteration in the content and distribution of iron, but did not increase the production of peroxides. Conclusion: These findings provide scientific evidence about changes occurring in biomarkers involved in the immunotoxicity of arsenic and offer a methodology for testing possible treatments against the deleterious action of this compound on the immune system.

Arsenic , Mice , Oxidative Stress , Acute Toxicity , Immune System
Article in Chinese | WPRIM | ID: wpr-847215


BACKGROUND: Skin transplantation is one of the most effective methods for treating large-area burns. How to effectively suppress the immune rejection after allogeneic skin transplantation is a problem that needs to be solved urgently. OBJECTIVE: To investigate the effect of human adipose derived mesenchymal stem cells (hADSCs) on the immunoregulation of skin grafts in different strains of mice. METHODS: Isolated hADSCs were cultured to the 3rd generation. Sixty ICR neonatal mice, 2-4 days of age, were randomly divided into four groups (n=15). The skin tissues of ICR neonatal mice were transplanted into adult C57BL/6 mice to establish a different strain of mouse skin graft immune rejection model. PBS and low dose (5×104), medium dose (10×104), high dose (20×104) hADSCs were injected into the model mice through tail vein, and the survival time of transplanted skin in each group was recorded. On the 7th day after operation, five mice from each group were randomly selected to remove their spleen and serum, and the expression of immune factors interleukin-10, tumor necrosis factor-α and interferon-γ were detected by RT-PCR and ELISA respectively. The transplanted part of the skin was taken to make pathological sections for observing the infiltration of lymphocytes. RESULTS AND CONCLUSION: Compared with the PBS group, the survival time of the skin was prolonged in the low dose hADSCs group; however, there was no significant difference between the two groups (P > 0.05). Compared with the PBS and low dose hADSCs groups, the survival time of the skin was significantly increased in the medium and high dose groups (P 0.05). Compared with the PBS group, the relative expression of tumor necrosis factor-α and interferon-γ in the spleen and serum was significantly decreased in the low, medium and high dose hADSCs groups (P < 0.05), whereas the level of interleukin-10 was significantly elevated in the medium and high dose hADSCs groups (P < 0.05). To conclude, the appropriate dose of hADSCs can significantly prolong the survival time of transplanted skin between different strains of mice, by regulating the expression of related immune factors in the recipient mice.

Article in Chinese | WPRIM | ID: wpr-847084


BACKGROUND: In the previous study, we have successfully prepared a silk fibroin/curcumin composite film, which possesses good physicochemical properties, sustained-release properties, antibacterial activity and biocompatibility. OBJECTIVE: To further observe the effect of the prepared silk fibroin/curcumin composite film, as the wound dressing, in the field of wound healing. METHODS: The silk fibroin/curcumin composite film was prepared by referring to the previously established methods. The mechanical properties and light transmittance of the prepared composite film were then investigated. Escherichia coli and Staphylococcus aureus were used as strains. The plate-counting technique was applied to evaluate the antibacterial activity of the light illuminated silk fibroin/curcumin composite film, silk fibroin/curcumin composite film without light exposure, and silk fibroin film without light exposure. The full-thickness excisional lesions were created on the dorsum of 20 Kunming mice. The wounds of 10 mice were covered with silk fibroin/curcumin composite film, and the wounds of other 10 mice were dressed with sterile gauze. The healing status and histological morphology of the wound sites were observed at 3, 7, and 14 days post operation. The animal experimental design and the protocols were approved by the Laboratory Animal Ethics Committee of Southwest University (approval number: IACUC-2019011). RESULTS AND CONCLUSION: (1) Compared to silk fibroin film, the fracture strength of silk fibroin/curcumin composite film increased significantly (P < 0.05), while the Young’s modulus of silk fibroin/curcumin composite film decreased significantly (P < 0.01). (2) Both silk fibroin film and the silk fibroin/curcumin composite film exhibited excellent transparency, but the silk fibroin/curcumin composite film showed a stronger absorption in visible light region at a wavelength of 400-450 nm. (3) Without light illumination, the silk fibroin/curcumin composite film exhibited stronger antibacterial activity than that of silk fibroin film. While, the silk fibroin/curcumin composite film with light illumination demonstrated stronger antibacterial activity than that of silk fibroin/curcumin composite film without light illumination. (4) The wound healing rate of the experimental group was higher than that of the control group at each time point (P <0.05). Analysis on histological morphology reveals that the length of regenerated epithelia of dermal tissue and the thickness of granulation tissue in the experimental group were greater than those in the control group at 3 and 7 days post operation (P < 0.01). While, the thickness of granulation tissue was smaller than that in the control group at 14 days post operation (P < 0.01). (5) The results indicated that the silk fibroin/curcumin composite film can facilitate skin wound healing.