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Chronic and excessive alcohol consumption leads to liver toxicity. There is a need to investigate effective therapeutic strategies to alleviate alcohol-induced liver injury, which remains the leading cause of liver-related morbidity and mortality worldwide. Therefore here, we looked into and evaluated how ethanol-induced hepatotoxicity was affected by coenzyme Q10 (CoQ10) and its analog, idebenone (IDE), on the NLRP3/caspase-1/IL-1 pathway. Hepatotoxicity induced in rats through the oral administration of gradually increasing dosages of ethanol (from 2 to 6 g/kg/day) over 30 days and the effect of CoQ10 (10 or 20 mg/kg) and IDE (50 or 100 mg/kg) were evaluated. Serum hepatotoxicity markers (ALT, AST, GGT, ALP, and TBIL), tissue oxidative stress markers and the mRNA expressions of IL-1ß, IL-18, TGF-ß, NF-κB, NLRP3, and caspase-1 were evaluated. Masson's trichrome staining was also used to visualize fibrosis in the liver tissue. The results indicated that ethanol exposure led to hepatotoxicity as well as considerable NLRP3/caspase-1/IL-1ß pathway activation. Moreover, CoQ10 or IDE treatment reduced measured parameters in a dosage-dependent manner. Thus, by inhibiting the NLRP3/caspase-1/IL-1 pathway, CoQ10 and IDE can prevent the hepatotoxicity caused by ethanol, although CoQ10 is more effective than IDE. This study will provide insight into new therapeutic avenues that take advantage of the anti-inflammatory and antioxidant properties of CoQ10 and IDE in ethanol-induced liver diseases.
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This study aimed to examine the effect of Phosphodiesterase 4 (PDE4) inhibition on Aquaporin-5 (AQP5) and its potential cell signaling pathway in the ovarian ischemia reperfusion (OIR) model. Thirty adult female rats were divided into five groups: Group 1; Control: Sham operation, Group 2; OIR that 3 hour ischemia followed by 3 hour reperfusion, Group 3; OIR + Rolipram 1 mg/kg, Group 4; OIR + Rolipram 3 mg/kg, Group 5; OIR + Rolipram 5 mg/kg. Rolipram was administered intraperitoneally to the rats in groups 3-4 and 5 at determined doses 30 minutes before reperfusion. From ovary tissue; Tumor necrosis factor-a (TNF-α), Cyclic adenosine monophosphate (cAMP), Nuclear factor kappa (NF-κB), Interleukin-6 (IL-6), Phosphodiesterase 4D (PDE4D), Mitogen-activated protein kinase (MAPK) and AQP5 levels were measured by ELISA. We also measured the level of AQP5 in ovary tissue by real-time reverse-transcription polymerase chain reaction (RT-PCR). In the OIR groups; TNF-α, NF-κB, IL-6, MAPK inflammatory levels increased, and cAMP and AQP5 levels decreased, which improved with the administration of rolipram doses. Also histopathological results showed damaged ovarian tissue after OIR, while rolipram administration decrased tissue damage in a dose dependent manner. We propose that the protective effect of PDE4 inhibition in OIR may be regulated by AQP5 and its potential cell signaling pathway and may be a new target in OIR therapy. However, clinical studies are needed to appraise these data in humans.
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Acuaporina 5 , Ovario , Inhibidores de Fosfodiesterasa 4 , Daño por Reperfusión , Rolipram , Animales , Femenino , Inhibidores de Fosfodiesterasa 4/farmacología , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Rolipram/farmacología , Rolipram/uso terapéutico , Ovario/efectos de los fármacos , Ovario/patología , Ovario/metabolismo , Ovario/irrigación sanguínea , Acuaporina 5/metabolismo , Ratas , AMP Cíclico/metabolismo , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
PURPOSE: The effect of urotensin II (U-II), a powerful endogenous vasoconstrictor substance, on the immune system and its mediators is very important. It was herein aimed to demonstrate the possible relationship between the calcineurin/nuclear factor of activated T-cells cytoplasmic 1/interleukin-2 (CaN/NFATc/IL-2) pathway and urotensin receptors (UTRs) in inflammatory response due to lipopolysaccharide (LPS). METHODS: An LPS-induced inflammation model was used on the human umbilical vein endothelial cells (HUVEC) cell line and drugs were applied accordingly, forming the following groups: Control Group, LPS Group, Agonist Group (10-8 âM U-II), Antagonist Group (10-6 âM palosuran), Tacrolimus (TAC) Group (10 âng/mL FK-506), Agonist â+ âTAC Group, and Antagonist â+ âTAC Group. Gene expression analyses were performed using real-time polymerase chain reaction (RT-PCR). RESULTS: In the analysis of the cell viability at 48 and 72 âh, there was a decrease in the Agonist Group, while in the Agonist â+ âTAC Group, the cell viability increased. In the Antagonist Group, cell viability was maintained when compared to the LPS Group, while in the TAC Group, this effect was reduced. The mRNA expression levels of UTR, CaN, NFATc, IL-2 receptor (IL-2R), IL-6 and nuclear factor kappa B (NF-κB) were higher in the LPS Group than in the Control Group, and even the UTR, CaN, NFATc, IL-2R were higher with agonist administration. This effect of the agonist was shown to be completely mitigated in the presence of the CaN inhibitor. CONCLUSION: U-II and its receptors can perform key functions regarding the endothelial cell damage via the CaN/NFATc/IL-2 pathway.
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Interleucina-2 , Lipopolisacáridos , Humanos , Lipopolisacáridos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Interleucina-2/metabolismo , Interleucina-2/farmacología , Calcineurina/metabolismo , Calcineurina/farmacología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objectives: Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats. Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3â hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation. Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL-1ß, TNF-α, and NF-κB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion. Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.
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PURPOSE: The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor ß1 (TGF-ß1), the high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process. MATERIALS AND METHODS: Bleomycin (0.1 âmL of 5 âmg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 âh after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF â+ âRM2 (pulmonary fibrosis model with bleomycin â+ âramelteon at 2 âmg/kg) and PF â+ âRM4 (pulmonary fibrosis model with bleomycin â+ âramelteon at 4 âmg/kg) at 2 and 4 âmg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining were performed on lung tissues. Lung tomography images of the rats were also examined. RESULTS: The levels of TGF-ß1, HMGB1, NLRP3, and interleukin 1 beta (IL-1ß) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p â< â0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume. CONCLUSIONS: The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.
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Proteína HMGB1 , Melatonina , Fibrosis Pulmonar , Animales , Ratas , Bleomicina/toxicidad , Proteína HMGB1/efectos de los fármacos , Proteína HMGB1/metabolismo , Pulmón , Melatonina/antagonistas & inhibidores , Melatonina/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56-100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.
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Polygonum , Úlcera Gástrica , Ratas , Animales , Indometacina/toxicidad , Antioxidantes/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Extractos Vegetales/farmacología , Ratas WistarRESUMEN
Objectives: Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 µg/kg lipopolysaccharide (LPS), SC), DEX group (200 µg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 µg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 µg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 µg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 µg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hr. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and caspase 3 and caspase 9 mRNA expression), biochemically (Superoxide dismutase activity (SOD), Glutathione (GSH), and malondialdehyde levels (MDA)) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-α, VEGF, caspase 9, and caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.
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The renin-angiotensin-aldosterone system (RAAS) is an important pathway that contributes to the pathophysiology of acute liver injury due to paracetamol toxicity. Omapatrilat, a RAAS-acting agent, inhibits both angiotensin converting enzyme (ACE) and neprilysin/neutral endopeptidase (NEP). The aim of the present study was to investigate the hepatoprotective effects of omapatrilat and examine the role of ACE/NEP pathway on the physiopathology of paracetamol toxicity. A total of 56 BALB/c mice were separated into seven groups: Control, 40 mg/kg omapatrilat only, 400 mg/kg paracetamol only, paracetamol and 140 mg/kg N-acetylcysteine and three groups with paracetamol and 10-40 mg/kg omapatrilat. Blood and liver tissue samples were studied through histopathological imaging, alanine transaminase (ALT) and aspartate transaminase (AST) liver function tests and oxidant/antioxidant biomarker measurements including superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA). ACE and NEP activities were also measured. Histopathological analysis revealed that paracetamol toxicity resulted in a number of apoptotic and necrotic cells in liver tissue samples. By contrast, with 40 mg/kg omapatrilat administration in toxicity-induced mice, hepatocytes were significantly improved and exhibited similar appearance to the control group. Biochemical measurements also supported these histopathological results. Omapatrilat pretreatment provided a dose-dependent reduction in oxidative stress and reversed paracetamol toxicity indications by reducing ALT and AST activities, increasing SOD activity and GSH levels and reducing MDA levels. Dose-dependent increase of ACE and NEP enzymes in omapatrilat groups was also observed. The results demonstrated promotion of antioxidant activity by omapatrilat and suppression of oxidative stress associated with acute liver injury. These findings revealed the potential role of ACE/NEP pathway in paracetamol toxicity and hepatoprotective effects of omapatrilat against oxidative stress.
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Chronic aluminium(Al) exposure can affect the antioxidant and glutaminergic systems through N-methyl-D-aspartate receptors (NMDAR). This study was aimed to investigate the neurotoxic effect of Al through different mechanisms in rat hippocampus and to evaluate the protective role of epigallocatechin gallate (EGCG), a well-known antioxidant, with simultaneous administration of Al,as well as post-treatment after Al exposure.For this purpose, aluminum chloride(AlCl3) was administered simultaneously with two different EGCG doses for 8 weeks as the first part of the study.In the second part of the study, after 4 weeks of AlCl3 pre-administration, two different EGCG doses were also administered during four additional weeks as post-treatment.Al administration led to oxidative stress and increased acetylcholinesterase levels.NMDAR subunit mRNA expressions were down-regulated by Al, which was apparent in NMDAR1/2B subunits.Simultaneous EGCG treatment has shown a better neuroprotective effect in terms of these mechanisms and represents novel approach for the prevention of neurodegenerative diseases likely to be induced by Al.
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Catequina , Fármacos Neuroprotectores , Síndromes de Neurotoxicidad , Ratas , Animales , Aluminio/toxicidad , Antioxidantes/farmacología , Ratas Wistar , Acetilcolinesterasa/metabolismo , Hipocampo , Síndromes de Neurotoxicidad/tratamiento farmacológico , Estrés Oxidativo , Catequina/farmacología , Catequina/uso terapéutico , Fármacos Neuroprotectores/farmacologíaRESUMEN
BACKGROUND/AIMS: Sepsis is one of the major problems encountered in intensive care units, causing organ damage and increasing mortality. Suberosin (SBR) is a type of coumarin with antioxidant and anti-inflammatory activities. The goal of this study is to explore the protective effects of SBR on the lungs in a rat model of sepsis. METHODS: Male Wistar rats were utilized in this study. A cecal ligation and puncture (CLP) model was applied to induce sepsis. Rats were separated into six groups with nine animals in each group, including healthy control, SBR, CLP, and CLP + SBR (5, 10, and 20 mg/kg) groups. Superoxide dismutase (SOD), glutathione (GSH) enzyme activities, and malondialdehyde (MDA) level were measured via enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were evaluated by real-time polymerase chain reaction (RT-PCR). Histopathological changes in the lungs were investigated with hematoxylin and eosin (H&E). RESULTS: MDA levels and GSH and SOD enzyme activities were negatively affected in the CLP group, but SBR treatment ameliorated these oxidative stress parameters in the SBR1-3 groups (p< 0.05). The mRNA expressions of TNF-α and IL-1ß were increased in the CLP group, and SBR treatment decreased those expression levels in a dose-dependent manner (p < 0.05). Organ damage and necrosis were seen in the CLP group and were alleviated in the SBR3 group. Immunohistochemical (IHC) analysis of lung tissues demonstrated decreased TNF-α and IL-1ß immunopositivity in the SBR1-3 groups (p< 0.05). CONCLUSIONS: SBR ameliorated sepsis-related lung injury in a dose-dependent manner. This compound has significant potential as a future agent in the treatment of sepsis.
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Lesión Pulmonar , Sepsis , Ratas , Masculino , Animales , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Wistar , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Cumarinas/farmacología , Ligadura/efectos adversos , Pulmón/patología , Punciones , Glutatión/metabolismo , Superóxido Dismutasa/metabolismo , ARN Mensajero , Modelos Animales de EnfermedadRESUMEN
PURPOSE: The aim of this study is to investigate insulin-like growth factor binding protein 5 (IGFBP5) expression in coronavirus disease 2019 (COVID-19) patients and its relationships with COVID-19 laboratory findings and plasma osteopontin (OPN) levels. MATERIALS AND METHODS: We enrolled 60 patients with COVID-19 and 30 healthy individuals in this study. mRNA expression of IGFBP5 was measured by RT-PCR. Plasma OPN levels were measured via the ELISA method. RESULTS: Plasma OPN levels were higher and IGFBP5 expression levels were lower in COVID-19 patients than in the healthy individuals (p â= â0.0057 and p â= â0.0142, respectively). Critically ill patients had higher OPN and lower IGFBP5 than non-critically ill patients. Patients with affected lungs demonstrated increased OPN and decreased IGFBP5 (p â= â0.00032 and p â= â0.044, respectively). Receiver operating characteristic (ROC) analysis indicated that IGFBP5 expression and OPN levels can be used discriminate non-critically from critically ill patients (p â= â0.049; p â= â0.0016, respectively). CONCLUSION: This study demonstrated that patients with a poor prognosis had increased OPN and decreased IGFBP5. High values of OPN and low values of IGFBP5 may be considered as signs of disease severity. Tissue-specific IGFBP5 expression may contribute to understanding the role of IGFBP5 in the lungs in COVID-19 cases.
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COVID-19 , Osteopontina , Humanos , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: Coronavirus-19 is still considered a pandemic that influences the world. Other molecular alterations should be clearer besides the increasing cytokine storm and pro-inflammatory molecules. Hypoxic conditions that induce HIF-1α lead to stimulate gene expression of STC-2 that targets PAPP-A expression. This study aimed to determine gene expression levels of PAPP-A, STC-2, and HIF-1α in COVID-19 infection. We also aimed to reveal the relationship of these genes with laboratory and clinical data of COVID-19 patients. MATERIALS AND RESULTS: We extracted RNA from peripheral blood samples of COVID-19(+) and COVID-19(-) individuals. The real-time PCR method was used to measure mRNA expression of PAPP-A, STC-2, and HIF-1α. Gene expression analysis was evaluated by the 2-ΔΔCt method. PAPP-A, STC-2, and HIF-1α mRNA expressions of severe patients were higher than healthy individuals (p = 0.0451, p = 0.4466, p < 0.0001, respectively). Correlation analysis of gene expression patterns of severe patients demonstrated a positive correlation between PAPP-A and STC-2 (p < 0.0001, r = 0.8638). CONCLUSION: This is the first study that investigates the relation of PAPP-A, STC-2, and HIF-1α gene expression in patients with COVID-19 infection. Besides the routine laboratory findings, PAPP-A, STC-2, and HIF-1α mRNA expressions may be considered to patients' prognosis as a sign of increased cytokines and pro-inflammatory molecules.
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COVID-19 , Glicoproteínas , Subunidad alfa del Factor 1 Inducible por Hipoxia , Péptidos y Proteínas de Señalización Intercelular , Proteína Plasmática A Asociada al Embarazo , COVID-19/genética , Expresión Génica , Glicoproteínas/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína Plasmática A Asociada al Embarazo/genética , ARN Mensajero/genética , SARS-CoV-2RESUMEN
AIM: We aimed to investigate the effects of rasagiline on acute lung injury that develops in the sepsis model induced with the cecal ligation and puncture in rats. MAIN METHODS: The rats were separated into the following six groups, Group 1: Sham, Group 2: Sham + Rasagiline 4 mg/kg, Group 3: Sepsis, Group 4: Sepsis + Rasagiline 1 mg/kg, Group 5: Sepsis + Rasagiline 2 mg/kg, Group 6: Sepsis + Rasagiline 4 mg/kg. A total of four holes were opened with a 16-gauge needle through the cecum distal to the point of ligation. KEY FINDINGS: Rasagiline treatment increased glutathione level and superoxide dismutase activity while decreased the malondialdehyde level after the sepsis. There was a statistically significant improvement in the doses of 2 mg/kg and 4 mg/kg. Rasagiline also increased Tnf-α, IL1ß, IL6, NF-κßand HMGB1 gene expressions in dose-dependent at 2 mg/kg and 4 mg/kg doses. In increased doses, rasagiline prevent the development of edema, the formation of inflammation, and hemorrhage. SIGNIFICANCE: Rasagiline exerts both antioxidant and anti-inflammatory effects on the cecal ligation and puncture induced acute lung injury in rats.
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Lesión Pulmonar Aguda , Sepsis , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Animales , Ciego/metabolismo , Ciego/patología , Modelos Animales de Enfermedad , Indanos , Ligadura , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Sepsis/tratamiento farmacológico , Sepsis/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine. AIM OF STUDY: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied. MATERIALS AND METHODS: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H2O2-induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined. RESULTS: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H2O2-induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-ß and IL-1ß levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group. CONCLUSION: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis.
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Abelmoschus/química , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antioxidantes/aislamiento & purificación , Células Cultivadas , Fibroblastos/efectos de los fármacos , Frutas , Humanos , Peróxido de Hidrógeno , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Medicina Tradicional , Ratones , Estrés Oxidativo/efectos de los fármacos , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , TurquíaRESUMEN
Objectives: We aimed to evaluate the impact of the tryptanthrin (TRP) compound, with antimicrobial and anti-inflammatory effects, on the excisional wound (EW) model. In an EW model in mice, we tried to explain the possible effect of TRP through vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) that contribute significantly to wound healing. Methods: A total of 90 BALB-C female mice aged 6 - 8 weeks were used in the present study. Animals were randomly divided into five groups. After creating the EW model, three different doses (1, 2.5, 5 mg/kg) of TRP compound were applied topically for 14 days, and wound closure rates were measured on days 0, 3, and 7. Vascular endothelial growth factor and MMP-9 were evaluated on days 3, 7, and 14 on wound explants and on day 14 on serum samples by enzyme-linked immunosorbent assay. Histopathological analysis was performed on wound explants. Results: After the EW model creation, significant healing of the wound areas was observed in the groups for which TRP was applied, especially on the third day. Moreover, in groups that received the third dose of TRP, the wound closure rate was 94%. It was found that the wound areas were closed due to the increase in TRP dose. In line with wound healing, VEGF and MMP-9 levels gradually rose on the third and seventh days and decreased on the 14th day. Conclusions: Tryptanthrin compound usage on the EW model increased wound healing and did not leave a scar after 14 days.
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PURPOSE/AIMS: This study focused on delineating the possible effects of roflumilast (ROF), a selective phosphodiesterase 4 (PDE4) inhibitor, in rats with cecal ligation and puncture (CLP)-induced polymicrobial sepsis, and investigated whether ROF can act as a protective agent in sepsis-induced lung damage. MATERIAL AND METHODS: Four experimental groups were organized, each comprising eight rats: Control, Sepsis, Sepsis + ROF 0.5 mgkg-1, and Sepsis + ROF 1 mgkg-1 groups. A polymicrobial sepsis model was induced in the rats by cecal ligation and puncture under anesthesia. Twelve hours after sepsis induction, the lungs were obtained for biochemical, molecular, and histopathological analyses. RESULTS: In the sepsis group's lungs, the TNF-α, IL-1ß, and IL-6 mRNA expression levels peaked in the sepsis group's lung tissues, and ROF significantly decreased these levels compared with the sepsis group dose-dependently. ROF also significantly decreased MDA levels in septic lungs and increased antioxidant parameters (SOD and GSH) compared with the sepsis group. Histopathological analysis results supported biochemical and molecular results. CONCLUSIONS: ROF, a PDE4 inhibitor, suppressed the expression levels of pro-inflammatory cytokines, alleviated lung damage (probably by blocking neutrophil infiltration), and increased the capacity of the antioxidant system.
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Lesión Pulmonar , Sepsis , Aminopiridinas , Animales , Benzamidas , Ciego/cirugía , Ciclopropanos , Modelos Animales de Enfermedad , Ligadura/efectos adversos , Pulmón , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , FN-kappa B , Punciones/efectos adversos , Ratas , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: A sepsis model was created, induced by cecal ligation and puncture (CLP), in juvenile rat groups. Milrinone (MIL), which is known to have a modulatory effect on pro-inflammatory cytokines, was administered to the designated rat groups in the early period before severe sepsis developed. The study was aimed at investigating the possible protective effects of milrinone on the lung and kidney tissues of rats in the late phase of sepsis. METHODS: The rat pups were divided into seven groups with six animals in each group: (1) healthy rats who received no drug; (2) CLP-S12 (sacrificed at hour 12); (3) CLP-S24 (sacrificed at hour 24); (4) CLP-MIL1-S12 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 12); (5) CLP-MIL1-S24 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 24): (6) CLP-MIL12-S24 (administered with 0.5 mg/kg milrinone at hour 12 and sacrificed at hour 24), (7) and CLP-MIL1,12-S24 (administered with 0.5 mg/kg milrinone at hours 1 and 12 and sacrificed at hour 24). RESULTS: Significant differences were found between the early and late administration of milrinone in terms of both molecular and histopathological results. The results showed that the tissues were significantly preserved in the groups in which milrinone had been started in the early period compared to the sepsis control groups and the groups in which milrinone had been started in the late period. CONCLUSIONS: In addition to the positive inotropic effects of milrinone, its immunomodulatory properties that result in decreased cytokine storm can be beneficial during early period of sepsis.
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Milrinona , Sepsis , Ratas , Animales , Milrinona/uso terapéutico , Milrinona/farmacología , Pulmón/patología , Riñón/patología , Punciones , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Modelos Animales de Enfermedad , LigaduraRESUMEN
OBJECTIVES: Our aim is to explain the relationship between Ang II and Scl in osteoporotic (OP) rats and the contribution of Scl in the antiosteoporotic effect mechanism of angiotensin receptor blockers (ARB). METHODS: This study consists of two sub-studies conducted on 4th and 12th weeks after ovariectomy. In study 1, treatment was started immediately after bilateral ovariectomy (OVX), while, in study 2, treatment was started 2 months after OVX. Two different doses of telmisartan (5 and 10 mg/kg) were administered with the aid of gavage for 30 days in both sub-study groups. RESULTS: Serum and tissue Scl, osteocalcin, osteopontin and tartrate-resistant acid phosphatase mRNA expressions were higher and bone mineral densities (BMD) and bone-specific alkaline phosphatase (BALP) mRNA expressions were found to be lower in the OVX groups compared with the sham group. In OVX groups where two different doses of telmisartan were administered, BMD and BALP mRNA expressions increased and serum and tissue Scl decreased. CONCLUSION: There may be a close relationship between angiotensin II and sclerostin in the development of osteoporosis. In this study, telmisartan administration showed an antiosteoporotic effect and significantly decreased the level of sclerostin. These results strongly support this relationship.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Densidad Ósea , Proteínas Morfogenéticas Óseas/metabolismo , Osteoporosis/metabolismo , Receptores de Angiotensina/metabolismo , Telmisartán/farmacología , Fosfatasa Alcalina/metabolismo , Angiotensina II/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Conservadores de la Densidad Ósea/farmacología , Modelos Animales de Enfermedad , Estrógenos/deficiencia , Femenino , Marcadores Genéticos , Osteocalcina/metabolismo , Osteogénesis/efectos de los fármacos , Osteopontina/metabolismo , Osteoporosis/etiología , Osteoporosis/prevención & control , Ovariectomía , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC-MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.
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Aminoácidos/sangre , COVID-19/sangre , SARS-CoV-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/diagnóstico , Cromatografía Liquida , Femenino , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , PronósticoRESUMEN
OBJECTIVES: We examined the antiosteoporotic effect of bosentan (Bose) by radiographic, histopathological, and molecular methods. MATERIALS AND METHODS: Rats were divided into 4 groups of 8 rats each: one control (Sham), one osteoporosis only (OP), and two osteoporosis groups treated with Bose doses of 50 and 100 mg/kg (OP+Bose50, OP+Bose100). Six weeks later, Bose was administered for eight weeks to animals undergoing ovariectomy. The left femoral bone of the rats was evaluated in vitro after surgical removal. Bone mineral density (BMD) was analyzed by Dual-energy X-ray absorptiometry (DEXA). Endothelin 1 (ET-1), ET-A, and ET-B expressions were examined by real-time polymerase chain reaction (real time-PCR). In addition, bone tissue was evaluated histopathologically. RESULTS: Compared with the osteoporosis group, Bose significantly increased BMD values at both 50 and 100 mg/kg doses. ET-1 mRNA levels were significantly higher in the OP group than in the Sham group, while ET-1 mRNA levels were significantly lower in Bose treatment groups. ET-A mRNA levels were significantly lower in the OP group than in the Sham group, while ET-A mRNA levels were significantly higher in Bose treatment groups. Histopathological results supported the molecular results. CONCLUSION: Our study is the first to demonstrate the molecular, radiological, and histopathological effects of Bose in preventing osteoporosis in rats.