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BACKGROUND: Gadolinium deposition in biological tissues was first reported in patients with renal failure. We aimed to investigate gadolinium deposition in the rat kidney after exposure to single and multiple doses of gadolinium and evaluate deposition for 1- and 3-month periods. We also aimed to determine any correlation between the amount of deposition and T1-weighted image intensity. METHODS: Seventy rats (5 animals per group) were included in the sample, and 9 groups received a single dose (0.3, 0.6, and 1.2 mmol/kg) of gadolinium, and 1 group for each dose was sacrificed at the end of the first day, week, and month. Four groups received weekly doses (0.3 and 0.6 mmol/kg) and were sacrificed at the end of 6 and 12 weeks. Measurement of T1 intensities was carried out with postinjection images before sacrifice, and deposition was determined using inductively coupled plasma mass spectrometry. RESULTS: The number of injections was associated with increased gadolinium deposition (P <.001) in the kidney. After the weekly injections, the deposited gadolinium levels did not significantly difer between the low and medium doses at the end of the sixth week (P=.067). There was no agreement between the observers regarding the measurement of T1 signal intensity in both single-dose and multidose experiments (P=.263 and P=.307, respectively). CONCLUSION: Deposition was dose dependent in the postinjection stage in contrast to the late stage in which deposition was not associated with dose or number of injections until the 12th week. T1 signal intensity measurement is unreliable for assessing deposition in the rat kidney.
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OBJECTIVE: The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. METHODS: 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. RESULTS: IL-1ß, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1ß, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. CONCLUSION: Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1ß, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.
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Isquemia Encefálica , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Pirimidinas , Ratas Wistar , Daño por Reperfusión , Animales , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Inflamasomas/metabolismo , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Modelos Animales de Enfermedad , Interleucina-1beta/metabolismo , Inhibidores de Fosfodiesterasa 5/farmacología , Inhibidores de Fosfodiesterasa 5/uso terapéuticoRESUMEN
OBJECTIVE: The study aimed to evaluate serum interleukin-28 levels in COVID-19 patients and correlate the results with disease severity. MATERIAL AND METHODS: This study included 90 patients who presented to the COVID-19 outpatient clinics, hospital wards, and intensive care units. Serum interleukin-28, C-reactive protein, lactate dehydrogenase, fibrinogen, d-dimer, and ferritin levels were measured. Patients were divided into 3 groups based on clinical severity to mild, moderate, and severe groups (each group consisted of 30 patients). RESULTS: There were significant differences in serum C-reactive protein, lactate dehydrogenase, fibrinogen, d-dimer, ferritin, and interleukin- 28 levels between all groups. The mean serum interleukin-28 levels of all patients were 383.74 ± 63.58 ng/L. The mean serum interleukin-28 levels were 335.52 ± 42.12 ng/L in the mild group, 366.88 ± 41.27 ng/L in the moderate group, and 453.46 ± 36.78 ng/L in the severe group. CONCLUSION: There were significant differences in comparisons of all pairs (P < .05). Interleukin-28 may be a promising biomarker for detecting disease severity in COVID-19 patients.
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This study investigated the synergistic protective effects of melatonin (MEL) and ascorbic acid (vitamin C, ASA) in treating sepsis-induced lung injury in rats. Rats were divided into five groups: control, cecal ligation and puncture (CLP), CLP + MEL, CLP + ASA and CLP + MEL + ASA. The effects of MEL (10 mg/kg), ASA (100 mg/kg) and their combination on oxidative stress, inflammation and histopathology were evaluated in septic rats' lung tissues. Sepsis-induced oxidative stress and inflammation were evident through increased levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS) and oxidative stress index (OSI); decreased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) and glutathione peroxidase (GPx); and elevated levels of tumour necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) in the lung tissue. Treatment with MEL, ASA and their combination significantly improved antioxidant capacity and reduced oxidative stress, with the combination treatment being more effective. The combination treatment also significantly reduced TNF-α and IL-1ß levels and improved peroxisome proliferator-activated receptor (PPAR), arylesterase (ARE) and paraoxonase (PON) levels in the lung tissue. Histopathological examination showed reduced oedema and lymphocyte infiltration with a lung tissue appearance similar to the control group. Immunohistochemical staining for caspase 3 demonstrated reduced immune positivity in the treatment groups. In conclusion, this study supports the potential synergistic protective effects of MEL and ASA in treating sepsis-induced lung injury. The combination therapy could effectively reduce oxidative stress, inflammation and improve antioxidant capacity in septic rats, suggesting a promising strategy for treating sepsis-induced lung injury.
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Lesión Pulmonar , Melatonina , Sepsis , Ratas , Animales , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Melatonina/farmacología , Melatonina/uso terapéutico , Factor de Necrosis Tumoral alfa/farmacología , Pulmón , Estrés Oxidativo , Glutatión/metabolismo , Inflamación/patología , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
Sepsis is a syndrome that includes physiological, pathological, and biochemical abnormalities resulting from the host immune response to infection. Despite the improved treatment modalities in recent years, the incidence and mortality of sepsis are still increasing. Sepsis immunopathology is increasingly attracting the attention of researchers. The successes experienced with immunotherapeutics in the treatment of cancer and coronavirus disease 2019, which are diseases with similar pathophysiological features and common immune defects with sepsis, have given rise to the hope that similar successes can be achieved in the treatment of sepsis. In this review, future perspectives on the immunopathology of sepsis and immunotherapeutics are presented to improve the current understanding of the disease.
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BACKGROUND/AIMS: Sepsis is an uncontrolled systemic infection, withcomplex pathophysiology that may result in acute lung organ damage and cause multiple organ failure. Although much research has been conducted to illuminate sepsis's complex pathophysiology, sepsis treatment protocols are limited, and sepsis remains an important cause of mortality andmorbidity in intensive care units.Various studies have shown that idebenone (IDE) possesses strong antioxidant properties, which inhibit lipid peroxidation and protect cells from oxidative damage. The present study aimed to evaluate the protective effects of IDE against lung injury in a cecal ligation and puncture (CLP)-induced sepsis rat model. METHODS: Male albino Wistar rats were used. The animals were divided into a healthy control (no treatment), CLP, IDE control (200 mg/kg), and CLP + IDE subgroups (50 mg/kg, 100 mg/kg, and 200 mg/kg), with nine rats in each group.IDE was administered 1 h after CLP induction.To evaluate the protective effects of IDE, lung tissues were collected 16 h after sepsis for biochemical, immunohistochemical staining, and histopathological examination. RESULTS: IDE significantly ameliorated sepsis-induced disturbances in oxidative stress-related factors, with its effects increasing in accordance with the dose.IDE also abolished histopathological changes in lung tissues associated with CLP.Furthermore, interleukin 1 beta (IL-1ß)and tumor necrosis factor-alpha (TNF-α) immunopositivity markedly decreased in the septic rats following IDE treatment. CONCLUSIONS: IDE largely mitigated the inflammatory response in sepsis-induced lung injury by decreasing free radicals and preventing lipid peroxidation. The results suggest that IDE may represent a potential novel therapeutic drug for sepsis treatment.
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Sepsis , Animales , Modelos Animales de Enfermedad , Pulmón , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Ubiquinona/análogos & derivadosRESUMEN
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
The aim of the study was to examine the protective effects and possible mechanism of gossypin against isoproterenol (ISO)-mediated myocardial damage in vivo and H9c2 cell damage in vitro. H9c2 cells were categorized into five groups. Viability was evaluated with MTT and LDH release in H9c2 cells. Apoptotic parameter analysis was performed with cytochrome c (Cyt-c), caspase-3 (CASP-3), and BCL2/Bax mRNA expression levels. In vivo, gossypin was administered orally to mice at doses of 5, 10, and 20 mg/kg for 7 days. ISO groups were injected with isoproterenol (150 mg/kg) subcutaneously (on 8th and 9th) for 2 days. Afterward, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) levels and Troponin-I (Tn-I) amount from their serum, oxidative stress parameters superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) levels, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1 ß), and NF-kB mRNA expression levels with inflammatory markers from heart tissue were evaluated. In addition, IL-1B, BCL-2, and cas-3 immunohistochemical staining was performed from heart tissue and TNF-a level was measured by ELISA method. Administration of Gossypin protected the cells by dose-dependent, eliminating the reduced cell viability and increased LDH release of ISO in H9c2 cells. In mice serum analyses, increased LDH, CK-MB levels, and Tn-I levels were normalized by gossypin. ISO administration in heart tissue is regulated by gossypin with increased SOD activity, GSH amount, TNF-α, IL-6, IL-1ß, and NF-kB mRNA expression levels and decreased MDA amount. Overall, the present results demonstrated that gossypin has a potential cardioprotective treatment for ischemic heart disease on in vivo and in vitro.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Flavonoides/farmacología , Infarto del Miocardio/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Cardiotoxicidad , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Isoproterenol , Masculino , Ratones Endogámicos BALB C , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , RatasRESUMEN
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.
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This study aimed to investigate the effects of blood glucose control and the kidneys' functions, depending on fasting, in the streptozotocin-induced diabetes model in rats via TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression in the present study. 32 Wistar albino rats were allocated randomly into four main groups; H (Healthy, n = 6), HF (Healthy fasting, n = 6), D (Diabetes, n = 10), DF (Diabetes and fasting, n = 10). Blood glucose and HbA1c levels significantly increased in the D group compared to the healthy ones (p < 0.05). However, the fasting period significantly improved blood glucose and HbA1c levels 14 days after STZ induced diabetes in rats compared to the D group. Similar findings we obtained for serum (BUN-creatinine) and urine samples (creatinine and urea levels). STZ induced high glucose levels significantly up-regulated TNF-α, NLRP-3, TGF-ß1 and VCAM-1 mRNA expression and fasting significantly decreased these parameters when compared to diabetic rats. Histopathological staining also demonstrated the protective effects of fasting on diabetic kidney tissue. In conclusion, intermittent fasting regulated blood glucose level as well as decreasing harmful effects of diabetes on kidney tissue. The fasting period significantly decreased the hyperglycemia-related inflammatory cytokine damage on kidneys and also reduced apoptosis in favor of living organisms.
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Ayuno/metabolismo , Hiperglucemia/genética , Inflamación/genética , Riñón/patología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Necrosis Tumoral alfa/genética , Molécula 1 de Adhesión Celular Vascular/genética , Animales , Apoptosis/genética , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Caspasa 9/metabolismo , Creatinina/sangre , Creatinina/orina , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/orina , Ayuno/sangre , Hemoglobina Glucada/análisis , Hiperglucemia/sangre , Hiperglucemia/patología , Hiperglucemia/orina , Inflamación/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , ARN Mensajero/metabolismo , Ratas Wistar , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Urea/orina , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
BACKGROUND: Benidipine is an L, N and T type calcium channel blocker drug that is widely used as an antihypertensive drug. OBJECTIVE: For the first time in the literature, it was aimed to investigate the effectiveness of benidipine in controlling epileptic seizure and preventing the development of neurodegeneration in epilepsy. METHODS: An experimentally epilepsy model was produced with pentylenetetrazole, and rats were divided into seven groups, in different benidipine treatment doses or with valproic acid combinations. The epileptic activities of all rats were recorded according to the Fisher&Kittner classification. Biochemical parameters, histopathological Caspase-3 activity, Wyler hippocampal sclerosis, gliosis and neuronal degenerations were investigated. RESULTS: It was found that in the post-hoc analysis of epileptic activities, there was a similar antiepileptic scores among the treatment groups. IL-1 level was found to be significantly lower in the benidipine 4 mg/kg group, and TNF-alpha was lower in the group given valproic acid+benidipine 2 mg/kg (p<0.05). The other biochemical parameters were not found to be significant. Neural degeneration levels in the brain tissues were statistically significant (p<0.001). Compared with the healthy group, the most neural degeneration was in the control group, the least neural degeneration was in the valproic acid+benidipine 4 mg/kg group. CONCLUSIONS: For the first time in the literature, benidipine, alone or combined with valproic acid, were found to have a statistically significant antiepileptic efficacy, and provided neuroprotection when combined with valproic acid. Benidipine will be a promising agent in the treatment of epilepsy with its antiepileptic and neuroprotective effects.
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Anticonvulsivantes/farmacología , Encéfalo/efectos de los fármacos , Dihidropiridinas/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Antihipertensivos/farmacología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar , Ácido Valproico/farmacologíaRESUMEN
This study aims to investigate the protective effect of roflumilast, a phosphodiesterase (PDE)-4 enzyme inhibitor, and demonstrate its possible role in the development prevention of cerebral ischemia/reperfusion injury (CI/RI) after stroke induced by carotid artery ligation in juvenile rats. The rats were randomly divided into five groups: healthy group without any treatment, healthy group administered with 1 mg/kg roflumilast, CI group not administered with roflumilast, CI group administered with 0.5 mg/kg roflumilast, and CI group administered with 1 mg/kg roflumilast. In the CI groups, reperfusion was achieved 2h after ischemia induction; in the roflumilast groups, this drug was intraperitoneally administered immediately after reperfusion and at the 12th hour. At the end of 24h, the rats were sacrificed and their brain tissues removed for examination. The mRNA expressions obtained with real-time PCR of IL-1ß, TNF-α, and NLRP3 significantly increased in the CI/RI-induced groups compared with the control group, and this increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Moreover, ELISA revealed that both IL-1 ß and IL-6 brain levels were significantly higher in the CI/RI-induced groups than in the controls. This increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Histopathological studies revealed that the values closest to those of the healthy group were obtained from the roflumilast groups. Nissl staining revealed that the Nissl bodies manifested normal density in the healthy and roflumilast-administered healthy groups, but were rare in the CI/RI-induced groups. Roflumilast treatment increased these decreased Nissl bodies with increasing doses. Observations indicated that the Nissl body density was close to the value in the healthy group in the CI/RI-induced group administered with 1 mg/kg roflumilast. Overall, roflumilast reduced cellular damage caused by CI/RI in juvenile rats, and this effect may be mediated by NLRP3.