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Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune-neuroendocrine system. Most immune cells express dopamine receptors and other dopamine-related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS-CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS-CoV-2 infection. COVID -19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID -19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS-CoV-2 infection.
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COVID-19 , Enfermedades del Sistema Nervioso , Humanos , SARS-CoV-2 , Dopamina , ARN Viral , Receptores DopaminérgicosRESUMEN
AIMS: Apoptosis may contribute to a considerable proportion of neuron death after acute cerebral ischemia, although the underlying mechanisms remain unknown. The purpose of this research is to investigate the effect of cerebral ischemia-reperfusion on miR-27a/smurf1 axis in rat cerebral cortex alone and in combination with chlorogenic acid. METHODS: To create a model of ischemic brain injury, nylon monofilament occlusion of the common carotid artery (CCAO) was used for 20 min. Chlorogenic acid (30 mg/kg) was given intraperitoneally (ip) 10 min before ischemia and 10 min before reperfusion. RESULTS: TUNEL staining of cerebral cortex neurons revealed an increase in the number of apoptotic neurons 24 h after reperfusion. At the molecular level, IR damage lowered bcl2 protein expression while simultaneously increasing bax levels and the bax/bcl2 ratio. Also, we observed higher miR-27a gene expression and higher TNF-α protein level as well as lower smurf1 protein expression after 24 h following CCAO. Treatment with chlorogenic acid significantly reduced the apoptotic damage and reversed molecular alterations in cerebral cortex neurons after IR. CONCLUSION: Our findings indicate that miR-27a/smurf1/TNF-α axis may play a regulatory function in cerebral cortex cell death, providing a new target for novel therapeutic approaches during transit ischemic stroke. It was also shown that chlorogenic acid could restore these molecular changes, demonstrating that it is an effective agent against cerebral cortex apoptotic damage after acute IR injury.
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Isquemia Encefálica , MicroARNs , Daño por Reperfusión , Ratas , Animales , Factor de Necrosis Tumoral alfa , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismo , Apoptosis , Isquemia Encefálica/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , MicroARNs/metabolismoRESUMEN
Tissue engineering and regenerative medicine (TERM) as an emerging field is a multidisciplinary science and combines basic sciences such as biomaterials science, biology, genetics and medical sciences to achieve functional TERM-based products to regenerate or replace damaged or diseased tissues or organs. Probiotics are useful microorganisms which have multiple effective functions on human health. They have some immunomodulatory and biocompatibility effects and improve wound healing. In this article, we describe the latest findings on probiotics and their pro-healing properties on various body systems that are useable in regenerative medicine. Therefore, this review presents a new perspective on the therapeutic potential of probiotics for TERM.
Tissue engineering and regenerative medicine can design processes or products to restore, repair, or replace injured or diseased cells, tissues or organs. It contains the generation and making use of therapeutic stem cells, and engineered scaffolds for the manufacture of artificial organs. This field focuses on the development and application of new treatments to heal tissues and organs as well as repair functions lost due to damage, defects, disease or aging. The World Health Organization has described probiotics as "live microorganisms that, when administered in sufficient amounts, confer a health advantage on the host". Probiotics are found naturally in certain foods, such as kimchi and fermented yogurt. They are also found in your gut, where they partake in a type of important bodily processes, such as vitamin production, digestion, mood regulation, and immune function. Probiotics with their suitable pro-healing effects on different systems of the body can be used in regenerative medicine. Probiotic bacteria induce their beneficial effects via proven mechanisms including pathogens killing, modulating the gut microbiota, immunomodulatory effects, and anti-diabetic, anti-obesity and anti-cancer functions. Moreover, recent studies indicated that probiotics could neutralize infections caused by COVID-19. Probiotics are healthy microorganisms that exert multiple positive effects on human health, especially through the battle against pathogens and repairing different types of body tissues.
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Probióticos , Medicina Regenerativa , Ingeniería de Tejidos , Materiales Biocompatibles , Cicatrización de Heridas , Humanos , Microbiota , AnimalesRESUMEN
BACKGROUND: Cyclosporine A (CsA)-induced cardiac interstitial fibrosis and cardiac hypertrophy are highly known phenomena; however, the basic mechanisms of CsA cardiotoxicity are unclear. The present study evaluated the role of the Transforming growth factor-beta (TGF-ß)/Smad3/miR-29b signaling pathway and CaMKIIδ isoforms gene expression in cardiac remodeling under CsA exposure alone or combined with moderate exercise. METHODS: A total of 24 male Wistar rats were divided into control, cyclosporine (30 mg/kg BW), and cyclosporine-exercise groups. RESULTS: After 42 days of treatment, the findings revealed a significant decline in miR-29 and miR-30b-5p gene expression and an increase in gene expression of Smad3, calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) isoforms, Matrix Metalloproteinases (MMPs), protein expression of TGF-ß, heart tissue protein carbonyl and oxidized LDL (Ox-LDL), and plasma LDL and cholesterol levels in the CsA-treated group compared to the control group. The CsA group presented greater histological heart changes such as fibrosis, necrosis, hemorrhage, infiltrated leukocyte, and left ventricular weight/heart weight than the control group. Moreover, combined moderate exercise and CsA relatively improved gene expression changes and histological alternations compared to the CsA group. CONCLUSION: TGF-ß-Smad3-miR-29 and CaMKIIδ isoforms may mainly contribute to the progression of heart fibrosis and hypertrophy due to CsA exposure, providing new insight into the pathogenesis and treatment of CsA-induced side effects on the heart tissue.
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Ciclosporina , MicroARNs , Ratas , Animales , Masculino , Ciclosporina/farmacología , Remodelación Ventricular , Ratas Wistar , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Fibrosis , MicroARNs/metabolismo , Isoformas de Proteínas/genética , Transducción de Señal , Expresión GénicaRESUMEN
As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes-induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes-induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM-tropisetron, and DM-glibenclamide groups. Streptozotocin (50 mg/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real-time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes-induced testis damages, lowered TLR4, TRAF6, IRAK1, NF-κB, and caspase3 protein expressions, and decreased TNF-α and IL-1 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4/IRAK1/TRAF6 signaling pathway and thereby the attenuation of NF-κB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes-induced testicular injuries.
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Complicaciones de la Diabetes , Diabetes Mellitus Experimental , Masculino , Ratas , Animales , FN-kappa B/metabolismo , Tropisetrón , Receptor Toll-Like 4/metabolismo , Estreptozocina , Diabetes Mellitus Experimental/metabolismo , Gliburida , Factor 6 Asociado a Receptor de TNF/metabolismo , InflamaciónRESUMEN
Background and purpose: The present study investigated the role of the prostaglandin I2/peroxisome proliferator activator receptor (PGI2/PPAR) signaling pathway in cardiac cell proliferation, apoptosis, and systemic hemodynamic variables under cyclosporine A (CsA) exposure alone or combined with moderate exercises. Experimental approach: Twenty-four male Wistar rats were classified into three groups, namely, control, CsA, and CsA + exercise. Findings/Results: After 42 days of treatment, the findings showed a significant enhancement in the expression of the ß-MHC gene, enhancement in protein expression of Bax and caspase-3, and a significant decline in the protein expression of Bcl-2 expression, as well as increased proliferation intensity in the heart tissue of the CsA group compared to the control group. Systolic pressure, pulse pressure, mean arterial pressure (MAP), QT and QRS duration, and T wave amplitude, as well as QTc amount in the CsA group, showed a significant increase compared to the control group. PPAR-γ and PGI2 showed no significant changes compared to the control group. Moderate exercise along with CsA significantly enhanced the protein expression of PPAR-γ and PGI2 and declined protein expression of Bax, and caspase-3 compared to those in the CsA group. In the CsA + exercise group, systolic pressure, MAP, and Twave showed a significant decrease compared to the CsA group. Moderate exercises along CsA improved heart cell proliferation intensity and significantly reduced ß- MHC gene expression compared to the CsA group. Conclusions and implications: The results showed moderate exercise alleviated CsA-induced heart tissue apoptosis and proliferation with the corresponding activation of the PGI2/PPAR-γ pathway.
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Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.
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Background: Alcohol consumption in pregnancy is associated with an increased risk of cardiovascular abnormalities, but the mechanisms are unknown. This study evaluated the impact of ethanol exposure on the offspring's aorta structural, functional, and molecular alterations on postnatal (PN) both on days 21 and 90. Methods: This experimental study was conducted at Urmia University of Medical Sciences (Urmia, Iran) in 2019. Twenty Pregnant Wistar rats on the seventh day of Gestation Day (GD) were randomly divided into two groups: control and ethanol-treated groups (n=10 per group). From the seventh day of GD throughout lactation, rats in the ethanol group were fed binge alcohol (4.5 g/Kg body weight) once daily. Systemic hemodynamic variables in the offspring were analyzed using waveform contour analysis 90 days after birth. On postnatal days (PN) 21 and 90, aorta wall histological alterations and the level of inflammatory factors were assessed in the aorta of male offspring. The statistical differences were examined via an independent samples t test. P<0.05 was considered to be statistically significant. Results: The results revealed that offspring in the ethanol group had higher systolic, diastolic, mean arterial pressure, and dicrotic pressure than the control group (P<0.001). The level of aorta tissue tumor necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-κ, and endothelin-1 were significantly higher in the ethanol offspring group than in the control group (P<0.001). Histopathological changes such as total aorta thickness, tunica media, tunica adventitia, elastin fiber thickness, fiber interval, and elastin/media ratio significantly increased in the aorta of the offspring of the ethanol group compared to the control group 21 and 90 days after birth. Conclusion: Our findings suggest that prenatal and early postnatal ethanol exposure-induced cardiovascular abnormalities are, in part, due to predisposing the aorta to atherosclerosis, which was mediated through the aorta wall remodeling and inflammation process.
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Elastina , Endotelina-1 , Animales , Aorta , Moléculas de Adhesión Celular , Etanol/efectos adversos , Femenino , Estudios de Seguimiento , Hemodinámica , Masculino , Embarazo , Ratas , Ratas Wistar , Factores de Necrosis TumoralRESUMEN
Diabetic peripheral neuropathy (DPN) is a common nerve disorder of diabetes. The aim of this study was to explore the protective effects of tropisetron in DPN. Type 1 diabetes was created by a single injection of streptozotocin (50 mg/kg, ip). Tropisetron (3 mg/kg, ip) was administered daily for 2 weeks. Our analysis showed that nerve fibers and their myelin sheaths were thinned with decreased myelinated fiber number in diabetic animals. The intensity of Bcl-2 staining decreased and the intensity of Bax staining increased in the sciatic nerves of diabetic rats by using immunohistochemical staining. Furthermore, diabetes significantly increased tumor necrosis factor-alpha, interleukin 1-ß (TNFα and IL-1ß) and Bax/Bcl-2 ratio in sciatic nerves of rats. However, intraperitoneal injection of tropisetron significantly reversed these alterations induced by diabetes. These findings suggest that tropisetron attenuates diabetes-induced peripheral nerve injury through its anti-inflammatory and anti-apoptotic effects, and may provide a novel therapeutic strategy to ameliorate the process of peripheral neuropathy in diabetes.
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Diabetes Mellitus Experimental , Neuropatías Diabéticas , Animales , Antiinflamatorios/uso terapéutico , Apoptosis , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/patología , Inflamación/tratamiento farmacológico , Interleucina-1/efectos adversos , Ratas , Estreptozocina/efectos adversos , Tropisetrón/uso terapéutico , Factor de Necrosis Tumoral alfa , Proteína X Asociada a bcl-2RESUMEN
Ethanol exposure during pregnancy induces cardiac fibrosis in the fetal heart. However, the mechanisms by which consumption of ethanol induces fibrotic changes are not known. Pregnant rats were received ethanol 4.5 g/kg BW once per day from the 7th day of pregnancy (GD7) throughout lactation. Our findings demonstrated that, area of fibrosis increased in cardiac tissue in the pups on both postnatal day twenty one (PN21) and postnatal day ninety (PN90) after prenatal and early postnatal period ethanol treatment compared with the controls. It was accompanied by a decline in the expression of SIRT1 protein along with the elevation of FOXO3a and TGF-ß protein expressions which were determined by western blot. Overall, our data reveal that prenatal alcohol usage increase in fibrotic regions in the pup hearts possibly by regulating TGF-ß, FOXO3a and SIRT1 protein levels. These are potential therapeutic molecular targets that can be modulated to protect heart against maternal ethanol exposure.
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Efectos Tardíos de la Exposición Prenatal , Sirtuina 1 , Animales , Animales Recién Nacidos , Etanol/toxicidad , Femenino , Fibrosis , Estudios de Seguimiento , Humanos , Masculino , Embarazo , Ratas , Factor de Crecimiento Transformador betaRESUMEN
Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.
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Enzima Convertidora de Angiotensina 2 , Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas/metabolismo , Humanos , Sistema Renina-Angiotensina/fisiología , SARS-CoV-2 , Transducción de SeñalRESUMEN
Coronavirus Disease 2019 [COVID-19], caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], has rapidly evolved into a global health emergency. Neopterin [NPT], produced by macrophages when stimulated with interferon [IFN-]gamma, is an essential cytokine in the antiviral immune response. NPT has been used as a marker for the early assessment of disease severity in different diseases. The leading cause of NPT production is the pro-inflammatory cytokine IFN-. Macrophage activation has also been revealed to be linked with disease severity in SARS-CoV-2 patients. We demonstrate the importance of NPT in the pathogenesis of SARS-CoV-2 and suggest that targeting NPT in SARS-CoV-2 infection may be critical in the early prediction of disease progression and provision of timely management of infected individuals.
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COVID-19 , Neopterin , Antivirales , COVID-19/diagnóstico , Citocinas , Humanos , Pronóstico , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Apoptosis is the main pathological aspect of neuronal injury after cerebral ischemia-reperfusion (I/R) injury. However the detailed molecular mediators are still under debate. The aim of this study is to explore the effect of cerebral I/R on miR-23a/TGF-ß-activated kinase 1 binding protein 3 (TAB3)/nuclear factor kappa B (NF-κB)/p53 axis in rat hippocampus alone and in combination with chlorogenic acid (CGA). Common carotid artery occlusion (CCAO) was performed by nylon monofilament for 20 min to establish a model of ischemic brain injury. CGA (30 mg/kg) was administered intraperitoneally (ip), 10 min prior to ischemia and 10 min before reperfusion. Examination of hippocampus neurons by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining showed that the number of apoptotic neurons was elevated at 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of p53 with a concomitant upregulation of cleaved-caspase3/phosphorelated-caspase3 ratio and cytochrome c level. Further miR-23b gene expression was significantly downregulated after 24 h of reperfusion. Also, we observed increased TAB3 and NF-κB protein expressions after 24 h following CCAO. Treatment with CGA significantly reduced the apoptotic damage and also reversed miR-23b gene expression, TAB3 and NF-κB protein expressions in hippocampus neurons in I/R rats. In conclusion our data suggest that miR-23b/TAB3/NF-κB/p53 axis could play a regulatory role in hippocampus cell death, which provide a new target for novel therapeutic interventions during transit ischemic stroke. It also demonstrated that CGA could reverse these molecular alterations indicating an effective component against hippocampus apoptotic insult following acute I/R injury.
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Isquemia Encefálica , MicroARNs , Daño por Reperfusión , Animales , Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/genética , Proteínas Portadoras , Ácido Clorogénico/farmacología , Modelos Animales de Enfermedad , Hipocampo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Ratas , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: Breast cancer is the second leading cause of death and the most common cancer among women. 10 to 20 percent of breast cancer samples have a negative triple phenotype that is more metastatic and more difficult to diagnose. Tumor invasion to other tissues and the formation of a secondary tumor depend on the epithelial to mesenchymal transition process, and the STAT3 pathway, which is associated with tumor proliferation and invasion and is the target gene for the drug, alantolactone. In this study, the EMT process is evaluated in negative triple-breasted cancer cells treated with alantolactone. METHODS: We used MDA-MB-231 cell line for assessing the survival rate of triple negative breast cancer cells and MTT test for determining alantolactone dose. We used three doses of 0.01 0.1, and 1 µM of alantolactone for evaluating the cell behavior in cancer invasion pathway. Real-time PCR was used to evaluate the expression of Vimentin, and N-cadherin genes. All of the tests were repeated thrice and the data were analyzed using Prism version 7.0. RESULTS: The expression of Vimentin and N-cadherin decreased significantly at 1 µM alantolactone compared to the control group, p < 0.05. CONCLUSION: Alantolactone affects the expression of Vimentin and N-cadherin through STAT3 signaling pathway and suppresses EMT process, metastasis and cancer invasion. This component may be used for treatment of patients with breast cancer.
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Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.
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Nefropatías Diabéticas/tratamiento farmacológico , Fibrosis/tratamiento farmacológico , Riñón/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Tropisetrón/uso terapéutico , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Fibrosis/patología , Fibrosis/prevención & control , Glucosa/metabolismo , Riñón/patología , Masculino , Proteínas/metabolismo , Ratas Wistar , EstreptozocinaRESUMEN
This study aimed to evaluate the effect of tropisetron on liver injury induced by diabetes. Thirty-five male Wistar rats were assigned to five groups (n = 7): control (C), tropisetron (T), diabetic (D), diabetic + tropisetron (D + T) and diabetic + glibenclamide (D + G). Diabetic rats were treated with tropisetron (3 mg/kg body weight/day) or glibenclamide (1 mg/kg/day) for two weeks. Liver from diabetic rats exhibited a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), cholesterol (Chol), triglycerides (TG), low-density lipoprotein (LDL), and atherogenic index, and a significant decrease in liver glycogen, serum albumin and high-density lipoprotein. Treatment with tropisetron significantly abrogated diabetes-induced perturbation in these parameters. These effects were equipotent with glibenclamide, suggesting that tropisetron treatment is associated with a hepatoprotective effect against diabetic injury. Therefore, the results of this study manifested the significance of using tropisetron as a promising remedial agent to improve diabetic complications.
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Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Experimental/complicaciones , Hepatopatías/prevención & control , Estrés Oxidativo/efectos de los fármacos , Tropisetrón/farmacología , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Glucemia/análisis , Complicaciones de la Diabetes/etiología , Complicaciones de la Diabetes/patología , Hepatopatías/etiología , Hepatopatías/patología , Masculino , Ratas , Ratas Wistar , Antagonistas del Receptor de Serotonina 5-HT3/farmacologíaRESUMEN
Tropisetron is a 5-HT3 receptor antagonist that exerts protective effect against DN. The aim of this study was to investigate the possible molecular mechanisms associated with the renoprotective effects of tropisetron in STZ-induced diabetic rats. Animals were subdivided into 5 equal groups; control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). For induction of type 1 diabetes, a single injection of STZ (55 mg/kg, i.p.) was administered to the animals. Diabetic rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) for 2 weeks. According to the conducted analysis, diabetes led to renal dysfunction (reduction in glomerular filtration rate and urine urea and creatinine as well as elevation in plasma urea and creatinine) and abnormalities in antioxidant defense system (reduction in TAC and elevation in MDA), compared with the control group, which was prevented by tropisetron treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting analysis demonstrated that SIRT1 gene expression decreased while FOXO3a and NF-κB gene expression as well as phosphorylated FOXO3a/total FOXO3a protein ratios and claudin-1 protein level increased in the kidney of diabetic rats compared with the control group. Herein, the results of this research showed that tropisetron treatment reversed these changes. Besides, all these changes were comparable with those produced by glibenclamide as a positive control. Hence, tropisetron ameliorated renal damage due to diabetic nephropathy possibly by suppressing oxidative stress and alteration of SIRT1, FOXO3a, and claudin-1 levels.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Tropisetrón/uso terapéutico , Animales , Claudina-1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Proteína Forkhead Box O3/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Ratas , Ratas Wistar , Sirtuina 1/metabolismoRESUMEN
Introduction: microRNAs (miRs) play a critical role in both physiological and pathological processes. Recent studies have shown that garlic and exercise training have many beneficial effects in different disorders including cardiovascular disease. However, their mechanisms have not been fully understood. This study sought to investigate the impact of garlic and voluntary training alone or together on themiR-126 and miR-210 gene expressions and cardiac angiogenesis. Methods: Male Wistar rats were divided into four groups (n=7): (1) Control, (2) Garlic, (3) Exercise, and (4) Garlic+ Exercise. Animals were gavaged with raw fresh garlic homogenate (250 mg/kg body weight/day) or were subjected to voluntary training alone or together for about 6 weeks. The expressions of miR-126 and miR-210 in the heart tissue were measured by real-time PCR and lipid profile in serum was assessed by enzymatic kits. Angiogenesis was determined by immuno staining detection of PECAM-1 and CD31 in the heart tissue. Results: Garlic and exercise up-regulated myocardial miR-126 (P < 0.01), miR-210 (P < 0.001)expressions, and angiogenesis (P < 0.001) which was evidenced by higher CD31 expression. Besides, combination of garlic and exercise amplified their effects on those parameters (P < 0.001). Moreover, both voluntary exercise and garlic alone (P < 0.01) or together (P < 0.001) markedly modulated serum lipid profile. Conclusion: Voluntary exercise and garlic treatment for 6 weeks enhanced myocardial angiogenesis. These alterations were partly due to the increment of miR-126 and miR-210 expressions in the heart tissue in relation to improvement in lipid profile.
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BACKGROUND: This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. METHODS: Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. RESULTS: A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. CONCLUSION: Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.
Asunto(s)
Curcumina/farmacología , Ciclosporina/toxicidad , Enfermedades Renales/inducido químicamente , Metaloproteínas/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Tasa de Filtración Glomerular , Inmunosupresores/toxicidad , Enfermedades Renales/prevención & control , Masculino , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Ratas , Ratas WistarRESUMEN
BACKGROUND: Diabetes mellitus (DM) is one of the most common diseases in the worldwide. Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency and beta cells apoptosis. Tropisetron as a 5-HT3 receptor antagonist has positive effects on the inflammation, apoptosis and glucose lowering. The aim of this study was to investigate the effect of tropisetron on ß-cells apoptosis and its possible pathways. METHODS: Animals were divided into five equal groups: the control, tropisetron, diabetes, tropisetron-DM and glibenclamide-DM (seven in each group). Tropisetron and glibenclamide were administrated for 2 weeks after type 1 diabetes induction. Real-time PCR, western blot analysis and TUNEL assay were performed. RESULTS: We found that tropisetron decreased blood glucose and increased insulin secretion. Protein expression of NF-κB was downregulated, while protein expression of SIRT1 upregulated after tropisetron treatment. Moreover, Bax/Bcl2 ratio decreased in tropisetron-DM group and finally, apoptosis improved in pancreas tissue. CONCLUSIONS: It seems that tropisetron administration improves STZ-induced apoptosis and diabetes in the animals. This effect might be resulted from involvement in NF-κB/ SIRT1 pathway.