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BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly cause gastric ulcers (GUs). We investigated the effects of sulforaphane (SF) and thymoquinone (TQ) in rats with acetylsalicylic acid (ASA)-induced GUs. MATERIALS AND METHODS: Thirty-five male Wistar-Albino rats were divided into five groups: control; ASA; ASA with vehicle; ASA + SF; and ASA + TQ. Compounds were administered by oral gavage before GU induction. GUs were induced by intragastric administration of ASA. Four hours after GU induction, rats were killed and stomachs excised. Total oxidant status, total antioxidant status, total thiol, nitric oxide, asymmetric dimethylarginine, tumor necrosis factor-alpha levels, superoxide dismutase activity, and glutathione peroxidase activity in tissue were measured. Messenger RNA expression of dimethylarginine dimethylaminohydrolases, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2, and nuclear factor kappa-light-chain-enhancer of activated B cells were analyzed. Renal tissues were evaluated by histopathologic and immunohistochemical means. RESULTS: SF and TQ reduced GU indices, apoptosis, total oxidant status, asymmetric dimethylarginine, and tumor necrosis factor-alpha levels, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase expressions (P < 0.001, P = 0.001). Both examined compounds increased superoxide dismutase activity, glutathione peroxidase activity, total antioxidant status, total thiol, nitric oxide levels, endothelial nitric oxide synthase, dimethylarginine dimethylaminohydrolases, HO-1, nuclear factor erythroid 2-related factor 2, and HO-1 expressions (P < 0.001). CONCLUSIONS: These results suggest that pretreatment with SF or TQ can reduce ASA-induced GUs via anti-inflammatory, antioxidant, and antiapoptotic effects. These compounds may be useful therapeutic strategies to prevent the gastrointestinal adverse effects that limit nonsteroidal anti-inflammatory drugs use.
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Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Benzoquinonas/farmacología , Mucosa Gástrica/efectos de los fármacos , Fármacos Gastrointestinales/farmacología , Isotiocianatos/farmacología , Úlcera Gástrica/prevención & control , Animales , Apoptosis/efectos de los fármacos , Benzoquinonas/uso terapéutico , Biomarcadores/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Fármacos Gastrointestinales/uso terapéutico , Inmunohistoquímica , Isotiocianatos/uso terapéutico , Masculino , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Sulfóxidos , Resultado del TratamientoRESUMEN
BACKGROUND: Pirfenidone (PF) is a potent antifibrotic and anti-inflammatory agent. We investigated the protective effect of PF against postoperative intra-abdominal adhesions. MATERIAL AND METHODS: Thirty male Sprague-Dawley rats were divided into three groups (n = 10 in each group). In group 1 (control), adhesion induction was performed by cecal abrasion, and no treatment was administered. In group 2 (vehicle), for 2 wk after adhesion induction, 0.4%-carboxymethylcellulose was administered by gavage. In group 3 (PF treatment), for 2 wk after adhesion induction, 500-mg/kg/d PF was administered by gavage. On the 15th postoperative day, the animals were killed, and cecal and peritoneal tissues were excised. The adhesions were graded macroscopically. The protein concentrations and mRNA expression levels of the following genes were measured in the tissues: matrix metallopeptidase-9 (MMP-9); tissue inhibitor of metalloproteinase-1 (TIMP-1); tumor necrosis factor-alpha (TNF-α); and transforming growth factor-beta 1 (TGF-ß1). The tissue samples were also evaluated histopathologically. RESULTS: Macroscopic and histopathologic evaluation showed that PF-reduced adhesion and inflammation (P < 0.001, P = 0.004, respectively). Pretreatment with PF-reduced TIMP-1, TNF-α, and TGF-ß1 protein concentrations (P < 0.001, P < 0.001, and P < 0.001, respectively) and mRNA expression levels (P = 0.030, P = 0.005, and P = 0.016, respectively) and increased MMP-9 protein concentrations (P < 0.001) and mRNA expression (P = 0.021). CONCLUSIONS: The findings of this study suggest that PF can be used as a protective agent to prevent the development of peritoneal adhesions and inflammation during the postoperative period.
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Antiinflamatorios no Esteroideos/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Piridonas/uso terapéutico , Adherencias Tisulares/prevención & control , Animales , Antiinflamatorios no Esteroideos/farmacología , Modelos Animales de Enfermedad , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Peritoneo/metabolismo , Peritoneo/patología , Piridonas/farmacología , Distribución Aleatoria , Ratas Sprague-Dawley , Adherencias Tisulares/metabolismo , Adherencias Tisulares/patología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-É£ (PPAR-É£), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-É£ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects.
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Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Bencimidazoles/farmacología , Benzoatos/farmacología , Captopril/farmacología , Isquemia/complicaciones , Ácido Oleanólico/análogos & derivados , Daño por Reperfusión/complicaciones , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Proteínas de Fase Aguda , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Arginina/análogos & derivados , Arginina/metabolismo , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Captopril/uso terapéutico , Creatina/sangre , Endotelina-1/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Lipocalina 2 , Lipocalinas/sangre , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Proteínas Proto-Oncogénicas/sangre , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/metabolismo , Telmisartán , Urea/sangreRESUMEN
AIM: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model. METHODS: We used 12-16 weeks-old Wistar-Albino rats that weigh 300-350 g. Rats (n, 6) were randomized into four groups (Control, IR, IR + CAP, IR + TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed. RESULTS: Urea, creatinine, TOS, OSI levels of IR + CAP, and IR + TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR + TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR + CAP and IR + TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR + CAP and IR + T groups than IR group. CONCLUSION: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.
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Lesión Renal Aguda/genética , Regulación de la Expresión Génica , MicroARNs/genética , Estrés Oxidativo , ARN/genética , Daño por Reperfusión/genética , Lesión Renal Aguda/etiología , Lesión Renal Aguda/metabolismo , Animales , Biomarcadores/metabolismo , Creatinina/metabolismo , Modelos Animales de Enfermedad , Masculino , MicroARNs/biosíntesis , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Urea/metabolismoRESUMEN
BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a major complication in clinical practice. Previous studies suggest that statins have pleiotropic effects in addition to cholesterol-lowering effects. In this study, we aimed to investigate the hepatoprotective role of two different doses of simvastatin (SV) pretreatment in rats with experimental hepatic I/R injury. METHODS: Adult male Sprague-Dawley rats were divided into four groups (n = 7 in each group) :control, I/R, I/R with 2.5-mg/kg SV, and I/R with 5.0-mg/kg SV. Before hepatic I/R was induced, SV was injected intraperitoneally at doses of 2.5 and 5.0 mg/kg. After 45-min ischemia and a 60-min reperfusion period, the animals were euthanized, and liver tissues were excised. Tissue levels of malondialdehyde and nitric oxide, and activities of superoxide dismutase, glutathione peroxidase, and catalase were measured. Liver tissues were also evaluated histopathologically and immunohistochemically. RESULTS: Histopathologic evaluation showed that 5.0-mg/kg SV reduced hepatic damage and apoptosis. Pretreatment with 5.0-mg/kg SV reduced malondialdehyde and nitric oxide levels (P < 0.01) and increased superoxide dismutase, glutathione peroxidase, and catalase activities significantly (P < 0.001, P < 0.01) in I/R with 2.5-mg/kg SV compared with I/R group. In addition, SV decreased Kupffer cell activation, and hypoxia-inducible factor-1α and vascular endothelial growth factor protein levels. CONCLUSIONS: The results of this study suggest that 5.0-mg/kg SV pretreatment may be protective against hepatic I/R injury. This effect can be achieved by antioxidant and antiapoptotic activities.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hepatopatías/prevención & control , Hígado/irrigación sanguínea , Daño por Reperfusión/prevención & control , Simvastatina/uso terapéutico , Animales , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hígado/enzimología , Hígado/patología , Hepatopatías/patología , Masculino , Distribución Aleatoria , Ratas Sprague-Dawley , Daño por Reperfusión/patologíaRESUMEN
PURPOSE: This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. METHODS: Fifty male Sprague Dawley rats (250-300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid-Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. RESULTS: Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. CONCLUSIONS: Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.
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Hesperidina , Daño por Reperfusión , Masculino , Ratas , Animales , Antígeno Nuclear de Célula en Proliferación , Antioxidantes , Ratas Sprague-Dawley , Estómago , Superóxido Dismutasa , Isquemia , Malondialdehído , Compuestos de Sulfhidrilo , Glutatión PeroxidasaRESUMEN
In our study, we aimed to examine possible prophylactic (P) or therapeutic (T) effects of boric acid (BA) on lipopolysaccharide (LPS) induced liver and kidney damages. Thirty-two rats were divided into four groups as control, LPS, BAP+LPS, and LPS+BAT. BA was given orally to the rats one hour before the intraperitoneal LPS administration in the BAP+LPS group and one hour after the LPS administration in the LPS+BAT group. Malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-6 (IL-6), IL-10, reduced glutathione (GSH), total oxidant and antioxidant status (TOS and TAS), semaphorin-3A (SEMA3A), cytochrome c (CYCS), and caspase-3 (CASP3) parameters were determined by ELISA method to monitor inflammation, oxidative stress, and apoptosis in the liver and kidney tissues of rats. In addition, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine (CREA), C-reactive protein (CRP), gamma glutamyl transferase (GGT), glucose (GLU), sodium (Na), potassium (K), and chlorine (Cl) biochemical parameters were measured in rat serums to monitor liver and kidney functions. Liver and kidney tissues were also examined histopathologically and immunohistochemically. All data were statistically analyzed. Our histological, biochemical, inflammatory, oxidative stress, and apoptotic findings showed that LPS causes serious damage to liver and kidney tissues. Boric acid application brought about significant improvements on the parameters. However, this improvement was seen in the BAP+LPS group, and the results of the LPS+BAT group were insufficient to improve. Our results showed that boric acid administration is effective on severe liver and kidney damage caused by LPS. It has been concluded that prophylactic application is more effective, while therapeutic application is insufficient.
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PURPOSE: The purpose of this study was to investigate the effects of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, on acute kidney injury in a rat model of crush syndrome model. METHODS: Sixty-four rats were separated equally into eight groups, sham (sterile saline ip), crush, crush + vehicle (DMSO ip), and crush + BM (10 mg/kg ip) (n = 8). All groups were also divided as 3 and 24 h after decompression. Crush injury was induced by 6 h of direct compression to both hind limbs of the rats with blocks weighing 3.6 kg on each side, followed by 3 and 24 h of decompression. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrotizing factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1) concentrations, tissue total oxidant status (TOS) and total antioxidant status (TAS) were measured in the kidneys. Serum creatine kinase (CK), blood urea nitrogen (BUN) and creatinine concentrations were also measured. Glomerular and tubular structures were examined histopathologically. Bcl-2 was measured using immunohistochemistry. Apoptosis was assessed using the TUNEL method. RESULTS: BM treatment reduced KIM-1, NGAL, TNF-α, TGF-ß1, TOS concentrations, and increased TAS concentrations in the kidneys 3 and 24 h after decompression. Serum CK, BUN and creatinine concentrations were also reduced with BM. BM treatment decreased apoptosis in crush-related AKI. The Nrf2 activator BM reversed the crush-induced changes in the experimental rats. CONCLUSION: BM treatment prevented the progression of crush-related AKI in rats possibly through its cytoprotective effects of being an antioxidant, anti-inflammatory and anti-apoptotic agent.
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Lesión Renal Aguda/tratamiento farmacológico , Lesiones por Aplastamiento/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Animales , Biomarcadores/análisis , Masculino , Ácido Oleanólico/farmacología , Ratas , Ratas WistarRESUMEN
BACKGROUND: This study aims to show the corrective effect of verbascoside on histomorphological and biochemical differences in the colon mucosa of rats in which colon ischemia-reperfusion (I/R) injury was induced. METHODS: Fifty Sprague Dawley male rats were divided into 5 groups, of control, sham, ischemia (I), I/R, and I/R+verbascoside. Ischemia and reperfusion were applied to the suitable groups for 30 minutes and 120 minutes respectively, and 10 mg/kg verbascoside was administered intraperitoneally. Histomorphological assessment was done in the colon tissues obtained, and the goblet cells were assessed using the Alcian blue method. Proliferating cell nuclear antigen (PCNA), TUNEL, and hypoxia-induced factor 1 (HIF-1α) assays were used to assess oxidative stress with the immunohistochemical method. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and total thiol (TT) levels were checked, for a biochemical analysis of oxidative stress. RESULTS: Compared with the I/R group, histomorphological differences were seen to be corrected in colon epithelium in the I/ R+verbascoside group. The goblet cell number increased and cell proliferation was increased, as seen with the PCNA assay; and apoptosis was decreased, as seen with the TUNEL assay. HIF-1α expression also decreased in the drug group. In the drug group, SOD, GSH-Px, TAS, and TT levels increased, but TOS, OSI, and MDA levels decreased. CONCLUSION: It was seen that verbascoside had a corrective effect on histomorphological and biochemical differences caused by I/R injury.
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Antioxidantes , Colon , Glucósidos , Mucosa Intestinal , Estrés Oxidativo , Fenoles , Daño por Reperfusión , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Colon/efectos de los fármacos , Colon/patología , Colon/fisiopatología , Modelos Animales de Enfermedad , Glucósidos/farmacología , Glucósidos/uso terapéutico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/fisiopatología , Masculino , Estrés Oxidativo/efectos de los fármacos , Fenoles/farmacología , Fenoles/uso terapéutico , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatologíaRESUMEN
Determining the blood glucose level is important for the prevention and treatment of diabetes mellitus. We developed a sensor system using Quartz Crystal Microbalance (QCM) to determine the blood glucose level from human blood serum. This study consists of two experimental stages: artificial glucose/pure water solution tests and human blood serum tests. In the first stage of the study, the QCM sensor with the highest performance was identified using artificial glucose solution concentrations. In the second stage of the study, human blood serum measurements were performed using QCM to determine blood glucose levels. QCM sensors were coated with phthalocyanines (Pcs) by jet spray method. The blood glucose values of 96 volunteers, which ranged from 71 mg/dL to 329 mg/dL, were recorded. As a result of the study, human glucose values were determined with an average error of 3.25%.
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Purpose: This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. Methods: Fifty male Sprague Dawley rats (250300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acidSchiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. Results: Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. Conclusions: Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.
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Animales , Ratas , Heridas y Lesiones , Reperfusión , Hesperidina , Isquemia , Animales de LaboratorioRESUMEN
OBJECTIVE: Oxidative stress is increased in patients with acute myocardial infarction (AMI). Statins reduce oxidative stress independent of their effect in reducing low-density lipoprotein cholesterol (LDL-C). The aim of the present study was to compare the effects of atorvastatin and rosuvastatin on oxidative status by investigating serum paraoxonase, serum arylesterase, total oxidant status, total antioxidant status (TAS) and oxidative stress index (OSI) in patients with AMI. METHODS: Seventy patients with AMI were randomized into 2 groups; total of 55 patients (19 females, 36 males) aged 32 to 86 years completed the study and were included in the analysis. Patients were treated with 80 mg atorvastatin or 40 mg rosuvastatin for 4 weeks. Lipid parameters and parameters of oxidative status were measured at admission and after 4-week statin treatment. RESULTS: After 4-week treatment, atorvastatin and rosuvastatin were associated with significant reduction in TAS, OSI, total cholesterol, and LDL-C levels. Serum paraoxonase level was significantly increased in both groups, while high-density lipoprotein cholesterol (HDL-C) level was significantly reduced in atorvastatin group. No statistically significant differences were found between atorvastatin and rosuvastatin in terms of actual difference in oxidative stress parameters. CONCLUSION: Atorvastatin and rosuvastatin have similar effects on oxidative status in patients with AMI. Rosuvastatin affected HDL-C level more favorably than atorvastatin.
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Atorvastatina/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Rosuvastatina Cálcica/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Rosuvastatina Cálcica/farmacología , Rosuvastatina Cálcica/uso terapéuticoRESUMEN
Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. RESULTS: Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. CONCLUSIONS: These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.
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Acetilcisteína/uso terapéutico , Antioxidantes/uso terapéutico , Alcaloides de Berberina/uso terapéutico , Sistema Biliar/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Fenantridinas/uso terapéutico , Acetilcisteína/administración & dosificación , Acetilcisteína/efectos adversos , Alanina Transaminasa/sangre , Amilasas/sangre , Animales , Antioxidantes/administración & dosificación , Antioxidantes/efectos adversos , Aspartato Aminotransferasas/sangre , Alcaloides de Berberina/administración & dosificación , Alcaloides de Berberina/efectos adversos , Bilirrubina/sangre , Modelos Animales de Enfermedad , Humanos , Lipasa/sangre , Masculino , Malondialdehído/sangre , Óxido Nítrico/metabolismo , Oxidantes/sangre , Estrés Oxidativo/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/sangre , Pancreatitis/metabolismo , Pancreatitis/patología , Peroxidasa/metabolismo , Fenantridinas/administración & dosificación , Fenantridinas/efectos adversos , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects.
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Lesión Pulmonar Aguda/metabolismo , Alcaloides de Berberina/química , Mucosa Intestinal/metabolismo , Estrés Oxidativo , Fenantridinas/química , Daño por Reperfusión/tratamiento farmacológico , Adyuvantes Inmunológicos/química , Animales , Antioxidantes/química , Masculino , Oxidantes/química , Oxígeno/química , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of malign diseases. Prolidase is a member of the matrix metalloproteinase family, plays a major role in collagen metabolism, cell growth, and matrix remodeling. Elevated serum prolidase activity have beendemonstrated in several types of carcinoma. The aim of this study is to investigate the serum prolidase activity, total oxidant status (TOS), total antioxidant status (TAS) and to evaluate their relationship with tumor stage, lymph node metastasis, and tumor size in patients with breast carcinoma. METHODS: Thirty-five patients with breast carcinoma and forty healthy controls were enrolled to this study.Serum TAS, TOS levels, and prolidase activities were measured and oxidative stress indices (OSI) were calculated. RESULTS: TOS, OSI levels and prolidase activities were significantly higher in the patients with breast carcinoma compared to the control group (P < 0.001, P < 0.001, P = 0.002, respectively).TAS levels were significantly lower in the in the patients with breast carcinoma compared to the control group (P = 0.016).Positive correlations were found between prolidase activity, TOS, OSI levels and tumor stage, lymph node metastasis, and tumor size. A negative correlation was found between TAS levels and tumor size,hovewer there were no correlationsbetween tas levels and stage of the tumor,as well as lymph node infiltration. CONCLUSION: We conclude that elevatedserum prolidase activity and oxidative stress may be associated with breast carcinoma. Increased serum prolidase activity may be related to stage and prognosis of breast carcinoma. KEY WORDS: Breast carcinoma, Oxidative stress, Proline dipeptidase.
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Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carcinoma/sangre , Dipeptidasas/sangre , Proteínas de Neoplasias/sangre , Adulto , Anciano , Antioxidantes/análisis , Neoplasias de la Mama/patología , Carcinoma/patología , Estudios de Casos y Controles , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Oxidantes/sangre , Estrés Oxidativo , Estudios Prospectivos , Carga TumoralRESUMEN
BACKGROUND: Accelerated apoptosis plays a vital role in the development of diabetic vascular complications. Ozone may attenuate diabetic nephropathy by means of decreased apoptosis-related genes. The aim of our study was to investigate the effect of ozone therapy on streptozotocin-induced diabetic nephropathy in rats. Also the histopathological changes in diabetic kidney tissue with ozone treatment were evaluated. METHODS: The rats were randomly divided into six groups (n = 7): control (C), ozone (O), diabetic (D), ozone-treated diabetic (DO), insulin-treated diabetic (DI), and ozone- and insulin-treated diabetic (DOI). D, DI, and DOI groups were induced by a single intraperitoneal injection of streptozotocin. Ozone was given to the O, DO, and DOI groups. Group DI and DOI received subcutaneous (SC) insulin (3 IU). All animals received daily treatment for 6 weeks. RESULTS: Expressions of caspase-1-3-9, HIF-1α, and TNF-α genes were significantly higher in D group compared to C group (p < 0.05 for all). Ozone treatment resulted in significant decrease in the expressions of these genes in diabetic kidney tissue compared to both C and D group (p < 0.05 for all). Caspase-1-3-9, HIF-1α, and TNF-α gene expressions were found to be lower in DOI group compared to C group (p < 0.05 for all). Also adding ozone treatment to insulin therapy resulted in more significantly decrease in the expressions of these genes in diabetic tissue compared to only insulin-treated diabetic group (p < 0.05 for all). Regarding histological changes, ozone treatment resulted in decrease in the renal corpuscular inflammation and normal kidney morphology was observed. Both insulin and ozone therapies apparently improved kidney histological findings with less degenerated tubules and less inflammation of renal corpuscle compared to D, DO, and DI groups. CONCLUSION: Ozone therapy decreases the expressions of apoptotic genes in diabetic kidney tissue and improves the histopathological changes.
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Caspasas/genética , Diabetes Mellitus Experimental , Nefropatías Diabéticas/genética , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ozono/uso terapéutico , Factor de Necrosis Tumoral alfa/genética , Animales , Apoptosis , Caspasas/biosíntesis , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Etiquetado Corte-Fin in Situ , Masculino , Oxidantes Fotoquímicos/uso terapéutico , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
AIMS: Acute myocardial infarction is a serious acute cardiac disorder and heart disease is still a major public health problem in adults. We investigated the effects of embelin (EMB) and carnosic acid (CA) in animals with isoproterenol (ISO)-induced myocardial injury. MAIN METHODS: Adult male Wistar-Albino rats were divided into four groups: control, ISO, ISO with EMB, and ISO with CA. Before myocardial injury was induced, drugs were administered by oral gavage. Myocardial injury was induced by subcutaneous injection of ISO hydrochloride for 2 consecutive days. Serum cardiac troponin I (cTnI), ischemia modified albumin (IMA), heart fatty acid binding protein (HFABP) levels and paraoxonase-1 (PON-1) activity, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), tumor necrosis factor-α (TNF-α) levels, superoxide dismutase (SOD) activity, and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of nuclear factor-kappa B (NF-κB), P38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2) were analyzed. In addition, cardiac tissues were evaluated histopathologically and immunohistochemically. KEY FINDINGS: All tested compounds reduced myocardial damage, apoptosis, cTnI, IMA, HFABP, TOS, and TNF-α levels, NF-κB, p38 MAPK, and phosphorylated c-Jun N-terminal protein kinase (pJNK 1/2) expressions. All tested compounds increased SOD activity, GSH-Px activity, TAS levels, TT levels, phosphorylated extracellular signal-regulated kinase (pERK 1/2), and Nrf2 expressions. SIGNIFICANCE: Our results suggest that EMB and CA pretreatment could reduce myocardial injury via antiinflammatory, antioxidant, and antiapoptotic effects.
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Abietanos/farmacología , Apoptosis/efectos de los fármacos , Benzoquinonas/farmacología , Cardiotónicos/farmacología , Infarto del Miocardio/prevención & control , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Isoproterenol/toxicidad , Masculino , Infarto del Miocardio/fisiopatología , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Measurements of blood ethanol concentrations must be accurate and reliable. The most important factors affecting blood ethanol stability are temperature and storage time. In this study, we aimed to compare ethanol stability in plasma samples at -20 °C for the different storage periods. MATERIALS AND METHODS: Blood samples were collected from intoxicated drivers (N=80) and initial plasma ethanol concentrations were measured immediately. Plasma samples were then stored at -20 °C and re-assessed after 2, 3, 4, or 5 months of storage. Differences between the initial and stored ethanol concentrations in each group (N=20) were analyzed using Wilcoxon matched-pairs test. The deviation from the initial concentration was calculated and compared with Clinical Laboratory Improvement Amendments (CLIA'88) Proficiency Testing Limits. Relationships between the initial concentrations and deviations from initial concentrations were analyzed by Spearman's correlation analysis. For all statistical tests, differences with P values of less than 0.05 were considered statistically significant. RESULTS: Statistically significant differences were observed between the initial and poststorage ethanol concentrations in the overall sample group (P<0.001). However, for the individual storage duration groups, analytically significant decreases were observed only for samples stored for 5 months, deviations from the initial concentrations exceeded the allowable total error (TEa). Ethanol decreases in the other groups did not exceed the TEa. CONCLUSION: According to our results, plasma ethanol samples can be kept at -20 °C for up to 3-4 months until re-analysis. However, each laboratory should also establish its own work-flow rules and criterion for reliable ethanol measurement in forensic cases.
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Intoxicación Alcohólica/sangre , Conducción de Automóvil , Criopreservación/métodos , Etanol/sangre , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Factores de TiempoRESUMEN
Paraquat (PQ) is an agrochemical agent commonly used worldwide, which can cause acute lung injury (ALI) and death. Hyperbaric oxygen treatment (HBOT) is a therapeutic method, but the mechanisms of the protective effect of HBOT on ALI remain elusive. The purpose of this study was to evaluate the effect of HBOT on acute lung injury induced by PQ in rats. Wistar Albino rats (n=21) were separated into three groups of seven animals each: control (C), PQ, and PQ + HBOT groups. 20 mg/kg PQ was administered intraperitoneally in PQ and PQ + HBOT groups to induce experimental lung injury. Three days after PQ treatment, PQ + HBOT group was administered 100% O2 at 2.0 ATA for 1 hour per day, for five consecutive days. At the end of the study, lung tissue was obtained for determining total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and histopathological determination. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-ß1 mRNA levels were assessed by quantitative reverse transcription-polymerase chain reaction. In addition, the inducible nitric oxide synthase (iNOS) level in the plasma was determined. Plasma iNOS, OSI, tissue TNF-α, TGF-ß1 and bFGF mRNA levels, and histological injury scores in PQ + HBOT group were significantly lower than PQ group. TAS level in PQ + HBOT group was significantly higher than PQ group. The findings suggest that HBOT could effectively ameliorate PQ-induced lung injury in rats.
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Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/terapia , Herbicidas/toxicidad , Oxigenoterapia Hiperbárica/métodos , Paraquat/toxicidad , Lesión Pulmonar Aguda/patología , Animales , Modelos Animales de Enfermedad , Masculino , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
INTRODUCTION: Total 25-hydroxyvitamin D [25(OH)D] is the most reliable indicator of vitamin D status. In this study, we compared two automated immunoassay methods, the Abbott Architect 25-OH Vitamin D assay and the Roche Cobas Vitamin D total assay, with the liquid chromatography-tandem mass spectrometry (LC-MS/MS). MATERIALS AND METHODS: One hundred venous blood samples were randomly selected from routine vitamin D tests. Two of the serum aliquots were analyzed at the Abbott Architect i2000 and the Roche Cobas 6000's module e601 in our laboratory within the same day. The other serum aliquots were analyzed at the LC-MS/MS in different laboratory. Passing-Bablok regression analysis and Bland-Altman plot were used to compare methods. Inter-rater agreement was analyzed using kappa (κ) analysis. RESULTS: The Roche assay showed acceptable agreement with the LC-MS/MS based on Passing-Bablok analysis (intercept: -5.23 nmol/L, 95% CI: -8.73 to 0.19; slope: 0.97, 95% CI: 0.77 to 1.15). The Abbott assay showed proportional (slope: 0.77, 95% CI: 0.67 to 0.85) and constant differences (intercept: 17.08 nmol/L; 95% CI: 12.98 to 21.39). A mean bias of 15.1% was observed for the Abbott and a mean bias of -14.1% was observed for the Roche based on the Bland-Altman plots. We found strong to nearly perfect agreement in vitamin D status between the immunoassays and LC-MS/MS. (κ: 0.83 for Abbott, κ: 0.93 for Roche) using kappa analysis. CONCLUSION: Both immunoassays demonstrated acceptable performance, but the Roche Cobas assay demonstrated better performance than the Abbott Architect in the studied samples.