RESUMEN
Carbon tetrachloride (CCl4) is a strong hepatotoxic agent. The ability of the anti-inflammatory agent, lactoferrin (LF), to alleviate hepatic inflammation in a Wistar rat model administered with carbon tetrachloride (CCl4) was examined. Thirty male Wistar rats were segregated into 5 groups (6 rats per group): Control group, LF group (300 mg LF/kg b. wt daily for three weeks), CCl4 group (1 ml CCl4/kg b. wt once orally), LF-protected group (300 mg LF/kg b. wt daily for 3 weeks followed by 1 mL CCl4/kg b. wt once orally), and LF-treated group (1 mL CCl4/kg b.wt once orally followed by 300 mg LF/kg b. wt orally every day for three weeks). Erythrogram, leukogram, activity of oxidative stress markers (Superoxide dismutase [SOD], Glutathione peroxidase [GPx], and Malondialdehyde [MDA]), and expression of hepatic paraoxonase-1 (PON1), interleukin (IL)-1ß, and IL-10 mRNA were determined. Histopathological examination of the hepatic tissue was carried out. CCl4 caused liver injury, loss of liver antioxidant activity of SOD and GPx, and a significant increase in the level of malondialdehyde in the serum. Moreover, CCl4 induced up-regulation of hepatic pro-inflammatory (IL-1ß) factors, and down-regulation of anti-inflammatory (IL-10 and PON1) factors. Based on histopathological examination, the hepatic tissues had severe inflammation and were damaged. However, LF mitigated the liver damage, oxidative stress, and hepatotoxicity caused by CCl4. Overall, these results suggest that LF-mediated immunological mechanisms alleviate CCl4-induced hepatic toxicity and provide a novel perspective on the potential use of LF for prophylactic and therapeutic applications in treating liver diseases.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Lactoferrina/farmacología , Administración Oral , Animales , Tetracloruro de Carbono/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Glutatión Peroxidasa/metabolismo , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Fluoroquinolones are some of the most common antibiotics used by clinicians all over the world. Levofloxacin, a fluoroquinolone, is used therapeutically in numerous countries; however, it can cause an increase in liver function tests and liver dysfunction. The current study was designed to determine the effect of Levofloxacin (40 mg/kg body weight (b.wt.) daily for 2 weeks) on rat liver function and oxidative stress markers as well as to evaluate the potential hepatoprotective effects of Moringa oleifera leaf extract as a known antioxidant herb. M. oleifera leaf extract was found to improve the hepatic dysfunction induced by Levofloxacin by recovering liver enzymatic activities (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transferase [GGT]) to normal levels. The extract also reversed the antioxidant imbalance as measured by catalase and superoxide dismutase activities as well as by reduced glutathione and malondialdehyde levels. Moreover, M. oleifera leaf extract induced anti-inflammation by improving the production of interleukin (IL)-10. Additionally, its presence attenuated the downregulation of IL-1 induced by Levofloxacin alone from hepatic tissue. It can be concluded that M. oleifera extract can help reduce the side effects caused by Levofloxacin administration.
Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Moringa oleifera , Extractos Vegetales/farmacología , Hojas de la Planta , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Levofloxacino , Hígado/metabolismo , Hígado/patología , Masculino , Moringa oleifera/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Ratas WistarRESUMEN
This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 µL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-ß (TGF-ß) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.
Asunto(s)
Tejido Adiposo/citología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Rinitis Alérgica/inmunología , Rinitis Alérgica/terapia , Animales , Células Cultivadas , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , Modelos Animales de Enfermedad , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Mucosa Nasal/patología , Mucosa Nasal/ultraestructura , Ratas , Rinitis Alérgica/sangre , Rinitis Alérgica/genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
BACKGROUND: Little is known about the potential adverse effects of a chronic zoonotic nematode Trichinella spiralis infection on hepatic inflammation and its relationship to paraoxonase (PON)-1 and butyrylcholinesterase (BuChE) activities. Therefore, we aimed to examine the effects of T. spiralis infection on hepatic synthesis of PON1. METHODS: Wistar rats were infected with 2500 first-stage larvae (L1) of T. spiralis, and serum PON1 and BuChE activities were evaluated. Hepatic expression levels of PON1, BuChE and various cytokines and chemokines [interleukin (IL)-1, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and transforming growth factor (TGF)-ß1] were evaluated for up to 9 weeks post-infection (p.i.). The effect of these changes on the degree of hepatic apoptosis was also investigated. RESULTS: Trichinella spiralis infection in rats induced significant decreases in serum PON1 activities from day 2 until week 7 p.i. and BuChE activity starting from day 4 until 2 weeks p.i. Moreover, T. spiralis infection increased serum pro-inflammatory cytokines IL-1, IL-6 and TNF-α as well as chemokines MCP-1, MIP-1α and TGF-ß1 during the enteral phase of the parasite life cycle. The anti-inflammatory cytokines IL-4 and IL-10 showed significant increases during the enteral phase for the former and the muscle phase for the latter. These were associated with hepatic inflammation and apoptosis. These events typically decreased hepatic PON1 and BuChE mRNA expression. CONCLUSIONS: Immune responses mounted against T. spiralis infection in rats were associated with hepatic inflammation and a subsequent decrease in serum PON1 and BuChE activities.
Asunto(s)
Arildialquilfosfatasa/metabolismo , Hepatitis/etiología , Trichinella spiralis/enzimología , Triquinelosis/complicaciones , Animales , Butirilcolinesterasa/metabolismo , Hepatitis/metabolismo , Hepatitis/patología , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Intestinos/enzimología , Intestinos/parasitología , Masculino , Músculos/enzimología , Músculos/parasitología , Ratas , Ratas Wistar , Triquinelosis/metabolismo , Triquinelosis/parasitologíaRESUMEN
We investigated the immunomodulatory and parasiticidal effects of garlic extract on coccidiosis caused by Eimeria vermiformis infection in male ICR mice. One group received garlic extract daily until the end of the experiment by the oral route from 10 days prior to oral infection with 300 sporulated E. vermiformis oocysts (infected-garlic(+)). The other group served as a control positive with E. vermiformis infection alone (infected-garlic(-)). In the infected-garlic(+) group, garlic extract treatment induced a significant reduction in fecal oocyst output when compared with the infected-garlic(-) group. Histopathological, immunohistochemical, and gene expression analysis for inflammatory cytokines in ileal tissues showed that the garlic extract treatment impaired intracellular development of E. vermiformis during the early stages by increasing the number of intraepithelial CD8(+) T cells and decreasing IL-10 expression. This induced cell cytotoxicity which was reflected by a decrease in oocyst numbers in the intestinal villi and the feces, indicating anticoccidial effects of the garlic extract. However, further studies to explore the precise mechanism of the observed effects of garlic treatment during Eimeria infection are needed to verify our results.
Asunto(s)
Antiparasitarios/administración & dosificación , Coccidiosis/tratamiento farmacológico , Eimeria/efectos de los fármacos , Ajo/química , Factores Inmunológicos/administración & dosificación , Extractos Vegetales/administración & dosificación , Animales , Linfocitos T CD8-positivos/inmunología , Coccidiosis/inmunología , Coccidiosis/parasitología , Heces/parasitología , Humanos , Intestino Delgado/inmunología , Intestino Delgado/parasitología , Masculino , Ratones , Ratones Endogámicos ICRRESUMEN
Alzheimer's disease (AD) is a devastating neurological condition characterized by cognitive decline, motor coordination impairment, and amyloid plaque accumulation. The underlying molecular mechanisms involve oxidative stress, inflammation, and neuronal degeneration. This study aimed to investigate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-exos) on AD and explore the molecular pathways involved, including the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation. To assess the potential of MSC-exos for the treatment of AD, rats were treated with AlCl3 (17â¯mg/kg/once/day) for 8 weeks, followed by the administration of an autophagy activator (rapamycin), or MSC-exos with or without an autophagy inhibitor (3-methyladenin; 3-MA+ chloroquine) for 4 weeks. Memory impairment was tested, and brain tissues were collected for gene expression analyses, western blotting, histological studies, immunohistochemistry, and transmission electron microscopy. Remarkably, the administration of MSC-exos improved memory performance in AD rats and reduced the accumulation of amyloid-beta (Aß) plaques and tau phosphorylation. Furthermore, MSC-exos promoted neurogenesis, enhanced synaptic function, and mitigated astrogliosis in AD brain tissues. These beneficial effects were associated with the modulation of autophagy and the PI3K/Akt/mTOR signalling pathway, as well as the inhibition of neuroinflammation. Additionally, MSC-exos were found to regulate specific microRNAs, including miRNA-21, miRNA-155, miRNA-17-5p, and miRNA-126-3p, further supporting their therapeutic potential. Histopathological and bioinformatic analyses confirmed these findings. This study provides compelling evidence that MSC-exos hold promise as a potential therapeutic approach for AD. By modulating the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation, MSC-exos have the potential to improve memory, reduce Aß accumulation, enhance neurogenesis, and mitigate astrogliosis. These findings shed light on the therapeutic potential of MSC-exos and highlight their role in combating AD.
Asunto(s)
Enfermedad de Alzheimer , Autofagia , Exosomas , Células Madre Mesenquimatosas , Transducción de Señal , Animales , Masculino , Ratas , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/terapia , Autofagia/efectos de los fármacos , Autofagia/fisiología , Modelos Animales de Enfermedad , Exosomas/metabolismo , Insulina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows. RESULTS: A comparative cohort study using serum specimens from Holstein-Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (P<0.001) in cows suffering from fatty liver. The area under the receiver operating characteristic curve (AUC-ROC) of PON1 activity for diagnosis of fatty liver was 0.973-0.989 [95% confidence interval (CI) 0.941, 1.000] which was higher than the AUC-ROC of aspartate aminotransferase (AST), lecithin-cholesterol acyltransferase (LCAT), alkaline phosphatase (ALP), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). We found that adding serum PON1 measurement to different batteries of serum diagnostic panels showed a combination of high sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver. CONCLUSIONS: The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.
Asunto(s)
Arildialquilfosfatasa/sangre , Enfermedades de los Bovinos/sangre , Hígado Graso/veterinaria , Animales , Biomarcadores/sangre , Bovinos/sangre , Enfermedades de los Bovinos/diagnóstico , Hígado Graso/sangre , Hígado Graso/diagnóstico , Femenino , Hígado/enzimología , Pruebas de Función Hepática/veterinaria , Curva ROCRESUMEN
The paraoxonase (PON) gene family includes three members, PON1, PON2 and PON3, aligned in tandem on chromosome 7 in humans and on chromosome 6 in mice. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. The major goal of this review is to highlight the modulation of each of the PONs by infective (bacterial, viral and parasitic) agents, which may shed a light on the interaction between infectious diseases and PONs activities in order to effectively reduce the risk of developing atherosclerosis.
Asunto(s)
Arildialquilfosfatasa/metabolismo , Aterosclerosis/enzimología , Infecciones Bacterianas/enzimología , Enfermedades Parasitarias/enzimología , Virosis/enzimología , Animales , Arildialquilfosfatasa/genética , Arildialquilfosfatasa/fisiología , Aterosclerosis/etiología , Aterosclerosis/inmunología , Infecciones Bacterianas/inmunología , Regulación de la Expresión Génica , Humanos , Inmunidad Innata , Enfermedades Parasitarias/inmunología , Virosis/inmunologíaRESUMEN
Paraoxonase-1 (PON1) is an HDL-associated enzyme with anti-atherogenic properties. Reduced PON1 activity has previously been observed in Nippostrongylus brasiliensis-infected rats. However, the effect of chronic zoonotic nematode infections on serum PON1 activity has not yet been studied. Therefore, we evaluated the effect of Trichinella spiralis infection on serum PON1 activity, the lipid profile, and oxidative stress in rats. There were significant reductions in serum PON1 activities (Day 2-Week 7 post-infection) in rats infected with T. spiralis, and these reductions were associated with significant increases in the serum levels of triglyceride and LDL/VLDL, as well as a significant reduction in the level of HDL. Moreover, T. spiralis infection was associated with a status of oxidative stress indicated by increased concentrations of superoxide dismutase and malondialdehyde. Given the zoonotic prevalence of T. spiralis and the cardioprotective role of PON1, further mechanistic research in this area is warranted.
Asunto(s)
Arildialquilfosfatasa/sangre , Lípidos/sangre , Estrés Oxidativo , Trichinella spiralis/fisiología , Triquinelosis/metabolismo , Animales , Colesterol/sangre , Lipoproteínas/sangre , Masculino , Ratones , Distribución Aleatoria , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Triquinelosis/sangre , Triquinelosis/enzimología , Triglicéridos/sangreRESUMEN
BACKGROUND: Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells. OBJECTIVE: We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG). METHODS: Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined. RESULTS: Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V. CONCLUSION: VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.
Asunto(s)
Células Madre Mesenquimatosas , Ovario , Animales , Médula Ósea , Células Madre Embrionarias , Femenino , Gonadotropinas , Oogénesis , RatasRESUMEN
BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
Asunto(s)
Diabetes Mellitus Experimental , Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Animales , Diabetes Mellitus Experimental/terapia , Ratas , Factor A de Crecimiento Endotelial Vascular , Cicatrización de HeridasRESUMEN
BACKGROUND: Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/ß-catenin signaling in liver development and generation. METHODS: Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/ß-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. RESULTS: iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/ß-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. CONCLUSION: This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.
Asunto(s)
Células Madre Pluripotentes Inducidas/citología , Hígado/citología , Andamios del Tejido/química , Regulación hacia Arriba , Vía de Señalización Wnt , Albúminas/metabolismo , Animales , Diferenciación Celular , Hepatocitos/citología , Células Madre Pluripotentes Inducidas/ultraestructura , Masculino , Ratas , Urea/metabolismo , alfa-Fetoproteínas/metabolismo , beta Catenina/metabolismoRESUMEN
BACKGROUND: Inflammation and oxidative stress are associated with cardiovascular diseases and underlying atherosclerosis. The high density lipoprotein (HDL)-associated paraoxonase-1 (PON1) enzyme is known to be involved in the protection of serum lipids from such oxidation. Nonetheless, the disturbances of lipid profile during nematode-infected model have not yet been studied. Therefore, we aimed to explore the effects of Nippostrongylus brasiliensis infection in male Wistar rats, a model of human gastrointestinal nematode infections, on hepatic PON1 synthesis and the levels of lipid parameters. MATERIALS AND METHODS: Nippostrongylus brasiliensis-infected rats fed standard and high-fat diets. Serum paraoxonase and arylesterase activities were measured on day 0, 2, 4, 7, and 14 post-infection (PI). Hepatic PONs and pro-inflammatory cytokines mRNA expression levels were evaluated in a standard diet-fed groups, and the disturbances in lipid profile as well as the levels of thiobarbituric acid reactive species (TBARS) and oxidized-LDL (Ox-LDL) were measured in high-fat diet-fed groups. RESULTS: We found that N. brasiliensis-infected rats fed the standard diet show a significant reduction in serum PON1 activity and down-regulation of hepatic PON1 mRNA expression as well as up-regulation of hepatic IL-1ß, IL-ß receptor (R), TNF-α, and TNFR1 mRNA expressions in association with hepatic recruitments of Kupffer cells and neutrohils. In the presence of the high-fat diet, N. brasiliensis infection increases serum triglycerides, total cholesterol, LDL/VLDL, TBARS and Ox-LDL as well as decreases serum HDL coinciding with a maximum serum PON1 reduction. CONCLUSIONS: Nippostrongylus brasiliensis infection can induce atherogenic lipid profile and reduce serum PON1 activity.
Asunto(s)
Arildialquilfosfatasa/metabolismo , Aterosclerosis/metabolismo , Lípidos/sangre , Lipoproteínas LDL/metabolismo , Infecciones por Nematodos/sangre , Nippostrongylus/crecimiento & desarrollo , Anciano , Anciano de 80 o más Años , Animales , Arildialquilfosfatasa/análisis , Grasas de la Dieta , Modelos Animales de Enfermedad , Ingestión de Energía , Humanos , Lipoproteínas LDL/análisis , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Ratas , Ratas Wistar , Estadística como AsuntoRESUMEN
Plasma butyrylcholinesterase (BChE) hydrolyzes ester-containing compounds such as succinylcholine, as well as acting as a scavenger against neurotoxic organophosphates (OPs). We previously found that Nippostrongylus brasiliensis infection makes rats more susceptible to OP toxicity by decreasing serum paraoxonase-1 (PON1) activity. In the present study, we examined the effects of N.brasiliensis infection on acetylcholinesterase (AChE) activity in plasma, red blood cells (RBCs), brain and diaphragm, as well as serum PON1 activity, in rats at day 7 after infection. N.brasiliensis infection significantly decreased plasma BChE and PON1 activities without significantly altering AChE activity in RBCs, brain and diaphragm. These results provide further insight into the unusual deleterious effects of intestinal nematode infections on body homeostasis.
Asunto(s)
Butirilcolinesterasa/sangre , Nippostrongylus/fisiología , Infecciones por Strongylida/enzimología , Acetilcolinesterasa/análisis , Acetilcolinesterasa/sangre , Animales , Arildialquilfosfatasa/sangre , Encéfalo/enzimología , Hidrolasas de Éster Carboxílico/metabolismo , Diafragma/enzimología , Eritrocitos/enzimología , Heces/parasitología , Masculino , Recuento de Huevos de Parásitos , Distribución Aleatoria , Ratas , Ratas Wistar , Infecciones por Strongylida/sangreRESUMEN
Adult worms of Strongyloides papillosus were surgically implanted into the duodenum and successfully established in Mongolian gerbils (Meriones unguiculatus). These worms persisted in the small intestine for at least four days after implantation. Following decreased fecal output, however, increased death rate and decreased survival time were observed. The increase in death rate and the decrease in survival time correlated with the increase in the number of implanted adult worms. Animals were then intraperitoneally inoculated with extracts from adult S. papillosus, and the pathogenetic effects of gastrointestinal (GI) motility were assessed by contrast radiography after oral administration of barium sulfate. Paralytic ileus was observed in the GI tracts of Mongolian gerbils and these symptoms intensified with increasing inoculation of adult worm extract. The results suggest that paralytic ileus underlies the subsequent death observed in Mongolian gerbils after implantation of adult S. papillosus. Furthermore, experimental infection with S. papillosus in Mongolian gerbils will provide a good model for laboratory investigations into GI motor disturbances in animals and humans caused by parasites.
Asunto(s)
Seudoobstrucción Intestinal/veterinaria , Strongyloides , Estrongiloidiasis/veterinaria , Animales , Antihelmínticos/uso terapéutico , Susceptibilidad a Enfermedades , Gerbillinae , Seudoobstrucción Intestinal/parasitología , Masculino , Mebendazol/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Conejos , Ratas , Ratas Wistar , Estrongiloidiasis/tratamiento farmacológico , Estrongiloidiasis/mortalidad , Estrongiloidiasis/parasitologíaRESUMEN
Infections with gastrointestinal nematodes provoke immune and inflammatory responses mediated by cytokines released from T-helper type-2 (Th2) cells. Infections with Trichinella species have been reported to differ by the host species. Previously, in rats, we observed acute liver inflammation in response to infection with Trichinella spiralis, and the rat hosts showed a series of biochemical changes characterized by a decrease in serum paraoxonase (PON) 1 activity associated with the down-regulation of hepatic PON1 synthesis. In the present study, we investigated the effect(s) of species differences on the immune response against T. spiralis infection by analyzing serum PON1 activity and the associated inflammatory/anti-inflammatory mediators in mice. There were inconsistent changes in the serum PON1 activity of mice infected with T. spiralis, and these changes were associated with significant increases in the serum levels of interleukin (IL)-2, IL-4, IL-10, IL-12 (p70), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α during the enteric phase of the infection, while the levels of IL-5 and interferon γ were significantly increased throughout the entire experimental period. Moreover, T. spiralis infection in mice was associated with little inflammatory cell infiltration in hepatic tissues. Given the zoonotic prevalence of T. spiralis, further mechanistic research in this area is warranted.
Asunto(s)
Hígado/parasitología , Trichinella spiralis/inmunología , Triquinelosis/veterinaria , Animales , Arildialquilfosfatasa/sangre , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Interferón gamma/sangre , Interleucina-5/sangre , Interleucinas/sangre , Hígado/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Triquinelosis/inmunología , Triquinelosis/parasitología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
AIM: The current study was designed to evaluate the potential hepatoprotective and immunomodulatory effects of copper-nicotinate complex (CNC) against methionine- and choline-deficient diet (MCDD)-induced fatty liver in rats. MATERIALS AND METHODS: Forty male Wistar rats were randomly allocated into one of four equal-sized groups (G1-G4). The G1 group was fed a balanced diet and kept under normal conditions; the G2 group received CNC orally at a dose of 0.043 mg/kg body weight, 3 times/week for 4 weeks, and a balanced diet; the G3 group was fed an MCDD for 4 weeks; and the G4 group was fed an MCDD and administered CNC at the same dose and route as G2. Blood samples were collected for the determination of serum enzyme activity. After 4 weeks of treatment, liver specimens were collected for the evaluation of the oxidative/antioxidative markers, cytokine gene expression, and histopathological examination. RESULTS: CNC improved MCDD-induced liver dysfunctions by recovering serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase activities to their normal levels. The glutathione (GSH) level and superoxide dismutase (SOD) activity significantly decreased, while lipid peroxidation (as reflected by malondialdehyde [MDA]) markedly increased in the liver tissue of the MCDD group. After cotreatment with MCDD and CNC, the GSH level and SOD activity markedly increased and the MDA level significantly decreased to return to normal levels. After cotreatment with MCDD and CNC, significant downregulation of the mRNA expression of hepatic interleukin (IL)-1ß, IL-4, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 genes was found. Moreover, CNC reduced fatty liver complications by reducing the number of hepatic vacuolations, degenerative changes in the hepatocytes, and hemorrhage. CONCLUSION: CNC has the potential to limit tissue injury and possibly prevent the progression to severe liver disease caused by an MCDD.
RESUMEN
It is known that hypersensitivity reactions in the gastrointestinal tract, which are primarily mediated by mast cells, are associated with a secretory response of the epithelium and often increased permeability to macromolecules. Studies to date have not examined the effects of hyperpermeability on the absorption of toxic substances normally present in the intestinal lumen such as bacterial LPS. In the present study, we observed that Strongyloides venezuelensis infection in mice decreases the mRNA expression of intestinal epithelial cell junctional molecules (occludin and zonula occludens 1) and increases portal endotoxin levels 4 h after intragastric administration of LPS (20 mg/kg body weight). Furthermore, an increase in the flux of immunoglobulin G into the intestinal lumen was observed 10 days postinfection (PI). An increased rate of LPS absorption was also seen in mice infected with Nippostrongylus brasiliensis on day 14 PI and rats concurrently infected with S. venezuelensis and N. brasiliensis on day 20 PI. On the other hand, infection with Eimeria vermiformis and Eimeria pragensis was not observed to enhance LPS absorption 4 h after intragastric administration of LPS (20 mg/kg body weight), although E. vermiformis infection did inhibit the epithelial cell mRNA expression of zonula occludens 1, but not occludin, on day 9 PI, resulting in a reduced immunoglobulin G flux than that produced by S. venezuelensis infection. Our results suggest that mastocytosis accompanying intestinal nematode infection increases the intestinal absorption of LPS into the portal circulation by suppressing the expression of tight junction molecules.
Asunto(s)
Coccidiosis/sangre , Eimeria , Absorción Intestinal , Lipopolisacáridos/sangre , Mastocitos/metabolismo , Mastocitosis/sangre , Nippostrongylus , Infecciones por Strongylida/sangre , Strongyloides , Estrongiloidiasis/sangre , Animales , Coccidiosis/complicaciones , Hipersensibilidad/sangre , Hipersensibilidad/etiología , Absorción Intestinal/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Mastocitosis/etiología , Proteínas de la Membrana/biosíntesis , Ratones , Ocludina , Fosfoproteínas/biosíntesis , Ratas , Ratas Wistar , Infecciones por Strongylida/complicaciones , Estrongiloidiasis/complicaciones , Uniones Estrechas , Factores de Tiempo , Proteína de la Zonula Occludens-1RESUMEN
Serum paraoxonase-1 (PON1) is an esterase associated with high-density lipoproteins in plasma and is involved in the detoxification of organophosphates (OP). We have previously reported a significant decrease in serum PON1 activity following Nippostrongylus brasiliensis infection in Wistar rats. In the present study we investigated the effects of decreased serum PON1 activity due to N. brasiliensis infection on acute toxicity induced by chlorpyrifos oxon (CPO) and paraoxon (PO) in rats. CPO and PO were dermally applied at doses of 8 mg/kg and 0.2 mg/kg body weight, respectively, to infected (on day 7 post-infection) and uninfected rats, after which acetylcholinesterase (AChE) activity was measured within the brain, diaphragm, plasma, and red blood cells, 4h after administration as a measure of toxicity. In addition, serum PON1 activity was measured immediately prior to administration of CPO and PO. N. brasiliensis infection significantly increased the degree of inhibition of AChE in the brain and diaphragm after treatment with CPO and PO in association with a significant reduction in PON1 activity. Likewise, similar findings were observed in the blood (plasma and RBCs) ChE activity after treatment with PO, but not CPO. These results indicate that N. brasiliensis infection makes rats more susceptible to CPO and PO toxicity, suggesting that gastrointestinal nematode infection might be a potential factor affecting OP toxicity.
Asunto(s)
Cloropirifos/análogos & derivados , Inhibidores de la Colinesterasa/toxicidad , Insecticidas/toxicidad , Parasitosis Intestinales/enzimología , Paraoxon/toxicidad , Enfermedades Parasitarias en Animales/enzimología , Infecciones por Strongylida/enzimología , Acetilcolinesterasa/metabolismo , Administración Cutánea , Animales , Arildialquilfosfatasa/sangre , Cloropirifos/toxicidad , Relación Dosis-Respuesta a Droga , Heces/parasitología , Parasitosis Intestinales/sangre , Parasitosis Intestinales/patología , Ratones , Nippostrongylus/fisiología , Recuento de Huevos de Parásitos , Enfermedades Parasitarias en Animales/sangre , Enfermedades Parasitarias en Animales/patología , Ratas , Ratas Wistar , Infecciones por Strongylida/patologíaRESUMEN
BACKGROUND: Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs). METHODS: In this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-ß as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and ß-actin expression. RESULTS: The therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-ß, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen. CONCLUSIONS: We conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment.