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Objectives: Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP). Materials and Methods: We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings. Results: Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups. Conclusion: Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.
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BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.
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Injúria Renal Aguda , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Fator de Necrose Tumoral alfa/metabolismo , Rim , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/metabolismo , IsquemiaRESUMO
Ovarian ischemia-reperfusion (I-R) injury may damage remote organs, including the lungs. We investigated whether apocynin, a NADPH oxidase inhibitor, might protect against ovarian I-R induced apoptosis in the lungs of rats. Bilateral ovarian I-R was induced for 3 h, then apocynin was applied at two concentrations. Lung tissue was evaluated using spectrophotometric and immunohistochemical methods. We found that I-R increased total oxidant status (TOS), oxidative stress index (OSI) and myeloperoxidase (MPO) levels, and immunostaining of nuclear factor kappa-B (NF-κB), light chain 3B (LC3B), interleukin 1-beta (IL-1ß), caspase-3 and tumor necrosis factor-alpha (TNF-α), but decreased superoxide dismutase (SOD) values. Apocynin application to I-R injured rats enhanced recovery of lung tissue oxidants and improved both histology and frequency of apoptosis.
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Lesão Pulmonar , Traumatismo por Reperfusão , Acetofenonas/farmacologia , Acetofenonas/uso terapêutico , Animais , Isquemia/patologia , Pulmão/patologia , Lesão Pulmonar/tratamento farmacológico , Estresse Oxidativo , Ratos , Reperfusão , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Ischemia-reperfusion is a common health problem leading to several health conditions. The pathophysiology of ischemia-reperfusion is quite complex. Oxidative stress and inflammatory response contribute to ischemia-reperfusion mechanisms. Various parameters like proinflammatory cytokines, reactive oxygen species, occur during ischemia-reperfusion . There are several ways to investigate these values through biochemical and histopathologic findings. Malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, interleukin 6, interleukin 1ß, tumor necrosis factor alpha, caspase-3, nuclear factor-kappa ß, and LC3B (microtubu le-associated protein light chain 3, LC3) can be evaluated among these indicators.
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OBJECTIVES: This study aimed to determine anti-inflammatory, antioxidant, and antiapoptotic properties of urapidil (Ura) against ovarian torsion detorsion (T/D) injury in rats. MATERIALS AND METHODS: 40 female Wistar albino rats were grouped as sham, T/D, T/D+dimethyl sulfoxide (DMSO), T/D+Urapidil (Ura) 0.5 mg/kg (low dose), and T/D+Urapidil (Ura) 5 mg/kg (high dose) groups. In treatment groups, Ura was administered intraperitoneally just before detorsion. Biochemical parameters (TAS, TOS, MDA, MPO, and SOD) and immunohistochemical (IL-1ß, TNF-α, NF-κB, LC3B, and Caspase-3) analyzes were performed. RESULTS: In the T/D group, OSI and MPO levels were elevated significantly while TAS values decreased compared with the sham group. A significant difference occurred in the low dose treatment group in TAS and OSI levels compared with the T/D group. In the high dose treatment group, significant elevation in TAS but reduction in OSI and MDA levels were observed compared with the T/D group. Immunohistochemical staining resulted in IL-1ß, TNF-α, NF-κB, LC3B, and caspase-3 immunopositivity in the T/D group, while Ura treatment decreased those parameters. Intensive congestion and hemorrhage were observed in the T/D group, but contrary to this, treatment groups had alleviated congestion and hemorrhage. CONCLUSION: These results suggest that Ura demonstrated protective effects against ovarian T/D injury via anti-oxidative, anti-inflammatory, and anti-apoptotic features.
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Oxidative stress-induced Ca2+ permeable transient receptor potential melastatin 2 (TRPM2) channels are expressed at high levels in the brain, appear to link neuronal excitability to cellular metabolism, and are involved in the pathogenesis of neurodegenerative disorders. We aimed to study the electrophysiological properties of TRPM2 channels in stellate cells of the mouse ventral cochlear nucleus (VCN) using molecular, immunohistochemical and electrophysiological approaches. In the present study, the real time PCR analysis revealed the presence of the TRPM2 mRNA in the mouse VCN tissue. Cell bodies of stellate cells were moderately labeled with TRPM2 antibodies using immunohistochemical staining. Stellate cells were sensitive to intracellular ADP-ribose (ADPR), a TRPM2 agonist. Upon the application of ADPR, the resting membrane potential of the stellate cells was significantly depolarized, shifting from -61.2 ± 0.9 mV to -57.0 ± 0.8 mV (P < 0.001; n = 21), and the firing rate significantly increased (P < 0.001, n = 6). When the pipette solution contained ADPR (300 µM) and the TRPM2 antagonists flufenamic acid (FFA) (100 µM), N-(p-amylcinnamoyl) anthranilic acid (ACA) (50 µM) and 8-bromo-cADP-Ribose (8-Br-cADPR) (50 µM), the membrane potential shifted in a hyperpolarizing direction. ADPR did not significantly change the resting membrane potential and action potential firing rate of stellate cells from TRPM2-/- mice. In conclusion, the results obtained using these molecular, immunohistochemical and electrophysiological approaches reveal the expression of functional TRPM2 channels in stellate neurons of the mouse VCN. TRPM2 might exert a significant modulatory effect on setting the level of resting excitability.
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Núcleo Coclear/fisiologia , Neurônios/fisiologia , Canais de Cátion TRPM/fisiologia , Adenosina Difosfato Ribose/farmacologia , Animais , Núcleo Coclear/metabolismo , Feminino , Masculino , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neurônios/metabolismo , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismoRESUMO
BACKGROUND: Gastric ulcer is a very common gastrointestinal disease that may be dangerous and even may lead to death. The current study was conducted to detect the prophylactic effects of agomelatine on indomethacin-induced gastric ulcer. METHODS: In this study, a total of 5 groups were created as the sham, ulcer, omeprazole, agomelatine 1 mg/kg and agomelatine 5 mg/kg groups. The effects of agomelatine on indomethacin-induced gastric injury were investigated. Total antioxidant and oxidant levels; the oxidant parameters like oxidative stress index and the inflammation markers such as tumor necrosis factor-α, interleukin-1ß, interleukin-6 and interleukin-10 levels in stomach tissue were determined by ELISA. In addition, the gastric mucosal injury occurred in stomach wall was examined with histopathological methods. RESULTS: While the levels of the inflammatory markers, total oxidant status and oxidative stress index increased at an obvious level especially in the indomethacin group, the total antioxidant status levels decreased. It was observed that these parameters were improved at a significant level in agomelatine 1 mg/kg and agomelatine 5 mg/kg groups when compared to ulcer group; and the results were similar to omeprazole group. It was also observed that our histopathological findings were consistent with all our other results. CONCLUSIONS: The results of this study showed that agomelatine usage in indomethacin-induced gastric ulcer model provides beneficial results.
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Acetamidas/uso terapêutico , Antiulcerosos/uso terapêutico , Indometacina/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Acetamidas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/farmacologia , Relação Dose-Resposta a Droga , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Úlcera Gástrica/metabolismoRESUMO
AIM: Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute kidney failure. The oxidative stress and inflammatory process are the underlying mechanisms of IR injury. It has been purposed in this study to research the possible protective effects of fraxin on kidney injury induced by IR. MATERIAL AND METHODS: 32 Sprague Dawley male rats were divided into 4 groups. The groups were organized as follows; sham, IR, IRâ¯+â¯fraxin 10â¯mg/kg, and IRâ¯+â¯50â¯mg/kg fraxin groups. Some oxidant, antioxidant and inflammatory parameters were evaluated in kidney tissues removed at the end of our experimental study. KEY FINDINGS: It was detected that the oxidant and proinflammatory markers increased and antioxidant parameters decreased in IR group but the results significantly reversed in treatment groups compared to IR group. And also, 8-OHdG, NF-κB, HAVCR1 immunopositivities were at severe levels and these results attenuated in IR fraxinâ¯+â¯10â¯mg/kg, and IRâ¯+â¯fraxin 50â¯mg/kg groups. SIGNIFICANCE: These presented results have shown that fraxin performed protective effects against kidney injury induced by IR.
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Injúria Renal Aguda/prevenção & controle , Antioxidantes/uso terapêutico , Cumarínicos/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Superóxido Dismutase/metabolismoRESUMO
Renal ischemia/reperfusion (I/R) injury resulting in acute renal failure, is a major clinical problem due to its high mortality rate. Renal I/R increases the reactive oxygen species, secretion of inflammatory cytokines, chemokines and other factors. This suggests that initiating the apoptosis process in the presence of oxidative stress may play a role in life-threatening conditions, such as ischemia. Ischemia reperfusion-induced renal damage can result in renal failure and death. Although many treatment procedures have been carried out to reduce or destroy renal I/R damage in experimental models, so far, a routine method of treatment has not yet been found. For this reason, the current study was planned to investigate the possible protective effects of evodiamine on tissue damage caused by ischemia-reperfusion in kidney tissue in rats and an experimental renal I/R model was used for this purpose. Four groups were formed in the study: the control, sham control, ischemia reperfusion (I/R), and evodiamine (10 mg/kg) + I/R groups. The effects of evodiamine against kidney I/R injury were investigated. TAS (total oxidant status), TOS (total oxidant status), interleukin-1ß (IL-1ß), IL-6, IL-10 and tumor necrosis factor-α levels were determined by enzyme-linked immunosorbent assay. The oxidative stress index was calculated from TAS and TOS levels. In addition, the renal ischemia reperfusion injury was examined histopathologically. The IL-10 and TAS levels in the I/R group decreased when compared with the control and Sham groups, while these levels increased in the evodiamine group. Histopathologic examination revealed that caspase 3 and nuclear factor-κB levels decreased in the evodiamine group compared with the I/R group. The application of evodiamine significantly reduced ischemia reperfusion-induced kidney damage due to its antioxidant, anti-inflammatory and antiapoptotic properties.
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Injúria Renal Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Quinazolinas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Inflamação , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Artéria Renal/cirurgia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Instrumentos Cirúrgicos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In this study, we evaluated the anti-oxidant and anti-inflammatory effect of caftaric acid against ulcer produced by indomethacin in gastric mucosa. Female Sprague Dawley albino rats were divided into five groups: control (saline group, n = 8), negative control (indomethacin group, n = 8), positive control (omeprazole group, n = 8), low dose therapy (caftaric acid, n = 8), and high dose therapy (caftaric acid, n = 8). At the end of the experiment, all rats were sacrificed and gastric mucosa samples were removed for macroscopic and biochemical analysis. In our study, we detected that oxidant parameter values and cytokine levels increased in the negative control group, but total antioxidant status reduced, whereas, cytokine and oxidant parameter levels were significantly reduced due to low and high doses of caftaric acid administration. But another important point to note is that high dose caftaric acid therapy performed gastroprotective effect as omeprazole. In the macroscopic evaluation, there were reductions in ulcer sizes with a low and high dose of caftaric acid administration in contrast to the negative control group. As a result of our study, caftaric acid showed anti-oxidant and anti-inflammatory effects in indomethacin-induced gastric ulcer in rats.
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Antiulcerosos , Antioxidantes , Fenóis , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Feminino , Indometacina/farmacologia , Oxidantes , Fenóis/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Úlcera Gástrica/tratamento farmacológicoRESUMO
The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na+ and Ca 2+ . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.
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ADP-Ribose Cíclica/análogos & derivados , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Canais de Cátion TRPM/antagonistas & inibidores , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Bloqueadores dos Canais de Cálcio/farmacologia , Catalase/metabolismo , Creatinina/sangue , ADP-Ribose Cíclica/farmacologia , Citoproteção , Modelos Animais de Doenças , Peróxido de Hidrogênio/metabolismo , Mediadores da Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Nifedipino/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Canais de Cátion TRPM/metabolismoRESUMO
BACKGROUND: Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-ß are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-ß immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol. METHODS: Thirty-two sprague Dawley male rats were randomly divided into four groups, including eight rats in each group as follows: Group 1: control; Group 2: ethanol 5 mL/kg; Group 3: ethanol 5 mL/kg+5 nmol/kg salusin-α; Group 4: ethanol 5 mL/kg+5 nmol/kg salusin-ß. RESULTS: The salusin-α level increased at a significant level in the ulcer group formed with ethanol (p<0.001); the change in the salusin-ß level is not significant. As for malondialdehyde (p<0.05) and myeloperoxidase (p<0.001), when compared with the control group, tumor necrosis factor-α (p<0.05) levels increased in the group to which ethanol was applied and decreased significantly with the application of salusins. Levels of GSH and IL-1ß did not change at a significant level. In addition, histopathologic analysis demonstrated that, in salusin-administered groups, mucosal injury and caspase-3 expressions were reduced. CONCLUSIONS: The suppression of salusin-α and salusin-ß on caspase-3 expression by means of their effects on oxidative injury and TNF-α levels shows that these two hormones could serve as anti-ulcerative agents.
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Antiulcerosos/farmacologia , Etanol/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/metabolismo , Caspase 3/biossíntese , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/sangue , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdeído/metabolismo , Peroxidase/metabolismo , Ratos , Fator de Necrose Tumoral alfa/sangueRESUMO
The potential toxic effects of several pesticides, including imidacloprid on non-target organisms have not been clearly established. Also, the chronic effects of non-toxic doses on cognitive function in mammals are unknown. In this study, the effects of different doses of imidacloprid on learning and memory of infant and adult rats were evaluated, and the expressions of genes synthesizing proteins known to be associated with learning in brain tissues were also documented. 0.5, 2 and 8 mg/kg doses of imidacloprid were administered to newborn infant and adult Wistar albino rats by gavage. Their learning activities were evaluated, and the expression levels of the inotropic glutamate receptor GRIN1, synoptophysin, growth-associated protein 43 and the muscarinic receptor M1 in hippocampus were determined by real-time PCR method. Learning activities were diminished significantly at 2 and 8 mg/kg doses in the infant model groups and at 8 mg/kg dose in adult rats. Also, expression levels of GRIN1, SYP and GAP-43 were found to be insignificantly altered. Only the expression of M1 were significantly changed in high doses of adult group. Thus imidacloprid in high doses causes deterioration in cognitive functions particularly in infant rats, and this deterioration may be associated with changes in the expressions of related genes.