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PURPOSE: The present study investigated the nephron-testicular protective effects of sesamin against cisplatin (CP)-induced acute renal and testicular injuries. METHODS: Thirty-two male Wistar rats were allocated to receive carboxymethylcellulose (0.5%, as sesamin vehicle), CP (a single i.p. 5 mg/kg dose), CP plus sesamin at 10 or 20 mg/kg orally for 10 days. RESULTS: Data analysis showed significant increases in serum urea, creatinine, interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α), as well as renal and testicular tissue malondialdehyde and nitric-oxide concentrations in CP-intoxicated rats in comparison to control animals. On the contrary, rats treated with CP only exhibited significantly lower (p < .05) serum testosterone, tissue glutathione, and activities of endogenous antioxidant enzymes compared to control rats. Histopathologically examining CP-intoxicated rats' tissues using H&E and PAS stains showed atrophied glomeruli, interstitial inflammatory cells, atypic tubular epithelium with focal apoptosis, and reduced mucopolysaccharide content. Further, immunohistochemical staining of the same group revealed an increase in p53 and cyclooxygenase-II (Cox-II) expression in renal and testicular tissues. Treatment with sesamin alleviated almost all the changes mentioned above in a dose-dependent manner, with the 20 mg/kg dose restoring several parameters' concentrations to normal ranges. CONCLUSIONS: In brief, sesamin could protect the kidneys and testes against CP toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic effects.
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Anti-Inflamatórios , Antioxidantes , Apoptose , Cisplatino , Dioxóis , Rim , Lignanas , Ratos Wistar , Testículo , Animais , Masculino , Lignanas/farmacologia , Lignanas/uso terapêutico , Cisplatino/toxicidade , Cisplatino/efeitos adversos , Ratos , Dioxóis/farmacologia , Antioxidantes/farmacologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Anti-Inflamatórios/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/patologia , Injúria Renal Aguda/metabolismo , Antineoplásicos/toxicidadeRESUMO
AIM: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats. METHODS: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue. RESULTS: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities. CONCLUSIONS: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.
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Tetracloreto de Carbono , Fibrose , Rim , Células-Tronco Mesenquimais , Animais , Masculino , Camundongos , Ratos , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/induzido quimicamente , Tetracloreto de Carbono/toxicidade , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Rim/patologia , Peroxidação de Lipídeos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Background: Hemolytic anemia (HA) is a serious health condition resulting from reduced erythrocytes' average life span. Echinochrome (Ech) is a dark-red pigment found in shells and spines of sea urchins. Aim: Studying the potential therapeutic effect of Ech on phenylhydrazine (PHZ)-induced HA in rats. Methods: Eighteen rats were divided into three groups (n = 6): the control group, the phenylhydrazine-induced HA group and the Ech group, injected intraperitoneally with PHZ and supplemented with oral Ech daily for 6 days. Results: Ech resulted in a considerable increase in RBCs, WBCs, and platelets counts, hemoglobin, reduced glutathione, catalase, and glutathione-S-transferase levels, and a significant decrease in aspartate & alanine aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, creatinine, urea, urate, malondialdehyde & nitric oxide levels in anemic rats. Histopathological examination of liver and kidney tissue samples showed marked improvement. Conclusion: Ech ameliorated phenylhydrazine-induced HA with a hepatorenal protective effect owing to its anti-inflammatory and antioxidant properties.
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Anemia Hemolítica , Estresse Oxidativo , Ratos , Animais , Antioxidantes/farmacologia , Anemia Hemolítica/induzido quimicamente , gama-Glutamiltransferase/farmacologia , Glutationa Transferase/efeitos adversos , Fenil-Hidrazinas/efeitos adversosRESUMO
Omentin (intelectin) was first detected in the visceral omental adipose tissue. It has mainly two isoforms, omentin-1 and -2, with isoform-1 being the main form in human blood. It possesses insulin-sensitizing, anti-inflammatory, anti-atherogenic, cardio-protective, and oxidative stress-decreasing effects. Omentin's cardiovascular protective actions are caused by the improved endothelial cell survival and function, increased endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, enhanced vascular smooth muscle cells (VSMCs) relaxation with reduced proliferation, decreased inflammation, and suppressed oxidative stress. Omentin may also have a potential role in different cancer types and rheumatic diseases. Thus, omentin is an excellent therapeutic target in many diseases, including diabetes mellitus (DM), metabolic syndrome (MetS), cardiovascular diseases (CVDs), inflammatory diseases, and cancer. This review demonstrates the physiological functions of omentin in ameliorating insulin resistance (IR), vascular function, and inflammation and its possible share in managing obesity-linked diseases, such as metabolic disorders, DM, and cardiovascular conditions.
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Vitamin D deficiency increases the risk of developing diabetes, dyslipidemia, and other chronic diseases. We aimed to investigate the relationship between vitamin D deficiency, glycemic levels, and lipid profiles in individuals with prediabetes and nondiabetes. This observational cross-sectional study was conducted on 249 adults who were divided into 2 groups based on the American Diabetes Association classification: nondiabetics and prediabetics. The serum vitamin D levels, lipid profiles, fasting blood glucose levels, hemoglobin A1c levels, fasting insulin levels, and insulin resistance (IR) were evaluated. The prevalence of vitamin D deficiency in all participants was 30.9%, and mean vitamin D levels were significantly [Pâ =â .0004] lower in prediabetics, who were more common in females. Furthermore, prediabetics had significantly higher serum triglycerides [Pâ =â .0006], and significantly lower serum high-density lipoprotein levels [Pâ =â .0148] than those nondiabetics. Serum cholesterol and low-density lipoprotein levels did not differ significantly between the 2 groups. 31.4% of all participants were overweight and 40.2% were obese. Furthermore, there was a strong correlation between vitamin D levels and IR and body mass indicesâ ≥â 25 in prediabetics [râ =â -0.92] [Pâ <â .001]. Finally, vitamin D levels had a significant inverse relationship with glycemic parameters and IR, particularly in obese participants, but there was no significant relationship with lipid profile. In conclusion, vitamin D deficiency is common in females, regardless of whether they are prediabetics, but is more prevalent in prediabetics. Vitamin D deficiency is associated with high triglycerides and low high-density lipoprotein levels, but there were no significant changes in total cholesterol or low-density lipoprotein levels. Furthermore, vitamin D levels were negatively correlated with both fasting blood glucose and hemoglobin A1c levels, and its deficiency was strongly associated with IR especially in obese patients despite there being no significant correlation with blood lipids.
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Diabetes Mellitus , Resistência à Insulina , Estado Pré-Diabético , Deficiência de Vitamina D , Adulto , Feminino , Humanos , Hemoglobinas Glicadas , Glicemia , Arábia Saudita/epidemiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D , Vitaminas , Diabetes Mellitus/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Lipídeos , Triglicerídeos , Colesterol , Lipoproteínas HDL , Lipoproteínas LDLRESUMO
Background: Some epithelial tumors express the carbohydrate antigen 125 (Cancer antigen-125, CA-125) and CA 19-9, especially ovarian and pancreatic tumors. Patients with non-Hodgkin lymphoma (NHL) were reported to have a close association between serum CA-125 levels and adverse prognostic factors with worse survival. We aimed to investigate CA-125 and 19-9 expression in nodal diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) tissues using immunohistochemistry (IHC) and their relations to clinicopathological manifestations and patients' survival. Methods: 65 cases of DLBCL NOS were examined. A modified mechanical pencil tip was used to construct Manual Tissue Micro-array (TMA) blocks. Immunohistochemical staining for CA-125 and CA 19-9 was performed and scored semi-quantitatively. All relations were analyzed using established statistical methodologies. Results: Aberrant expression of CA 19-9 was detected in 12% of cases without any expression of CA-125. Moreover, 75% of the CA 19-9 positive cases were statistically significantly associated with anemia and performance status 1. Also, 75% of the CA 19-9 positive cases were females. Conclusions: CA 19-9 was aberrantly expressed in 12% of nodal DLBCL NOS cases and significantly related to anaemia and performance status but not to survival. In cases of DLBCL NOS, CA 19-9 expression cannot be considered an independent prognostic factor. CA-125 was not expressed in nodal DLBCL NOS tissues, necessitating re-evaluation studies. Therefore, it is advised to conduct more research to clarify the potential correlation between serum and tissue CA 19-9 levels and other clinic-pathological characteristics of nodal and extranodal DLBCL NOS patients.
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Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Feminino , Humanos , Masculino , Antígeno Ca-125 , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , PrognósticoRESUMO
Asthma is a persistent inflammatory disease of the bronchi characterized by oxidative stress, airway remodeling, and inflammation. Echinochrome (Ech) is a dark-red pigment with antioxidant and anti-inflammatory activities. In this research, we aimed to investigate the effects of Ech against asthma-induced inflammation, oxidative stress, and histopathological alterations in the spleen, liver, and kidney in mice. Mice were divided into four groups (n = 8 for each): control, asthmatic, and asthmatic mice treated intraperitoneally with 0.1 and 1 mg/kg of Ech. In vitro, findings confirmed the antioxidant and anti-inflammatory activities of Ech. Ech showed antiasthmatic effects by lowering the serum levels of immunoglobulin E (IgE), interleukin 4 (IL-4), and interleukin 1ß (IL-1ß). It attenuated oxidative stress by lowering malondialdehyde (MDA) and nitric oxide (NO) contents and increasing reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase (GST), and catalase (CAT) in the liver, spleen, and kidney. Moreover, it protected asthma-induced kidney and liver functions by increasing total protein and albumin and decreasing aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, and uric acid levels. Additionally, it ameliorated histopathological abnormalities in the lung, liver, spleen, and kidney. Additionally, molecular docking studies were used to examine the interactions between Ech and Kelch-like ECH-associated protein 1 (Keap1). PCR and Western blot analyses confirmed the association of Ech with Keap1 and, consequently, the regulatory role of Ech in the Keap1-(nuclear factor erythroid 2-related factor 2) Nrf2 signaling pathway in the liver, spleen, and kidney. According to our findings, Ech prevented asthma and its complications in the spleen, liver, and kidney. Inhibition of inflammation and oxidative stress are two of echinochrome's therapeutic actions in managing asthma by modulating the Keap1/Nrf2 signaling pathway.
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Asma , Fator 2 Relacionado a NF-E2 , Animais , Camundongos , Ovalbumina , Proteína 1 Associada a ECH Semelhante a Kelch , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Asma/tratamento farmacológico , Transdução de Sinais , InflamaçãoRESUMO
The occurrence of worsening pulmonary function has been connected to hypothyroidism (HPO). Hesperidin (HES) was suggested to have antioxidant, anti-proliferative, and anti-inflammatory potential. Our study's objective was to determine whether HES could reduce carbimazole (CBZ)-induced lung injury more effectively than Eltroxin (ELT) in adult male albino rats or not. At random, 32 rats were distributed into four groups: Group I: normal control, to induce HPO, the remaining three groups were given CBZ (20 mg/kg/day) dissolved in distilled water for 1 week. They were then split up into three groups. Group II: orally administered CBZ (20 mg/kg b.w in water/day), Group III: HES (200 mg/kg/day) dissolved in 1% carboxymethyl-cellulose + CBZ treated, and Group IV: ELT (0.045 mg/kg/day) dissolved in distilled water + CBZ treated. All treatments were delivered for 12 weeks. Blood was collected to assess thyroid-stimulating hormone (TSH) and thyroid hormones (THs). Lung injury was evaluated based on the pulmonary content of interleukin (IL)-35, IL-6, and tumor necrosis factor-alpha (TNF-α), along with the estimation of lipid peroxidation, catalase, glutathione levels, superoxide dismutase, heme oxygenase-1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). The histological, ultrastructural, and immunohistochemical study of nuclear factor Kappa-B (NF-κB) and inducible nitric oxide synthase (iNOS), together with estimating the proliferation of cells using Antigen Ki-67 in lung tissue were performed. HES and ELT primarily suppressed variable lung damage mechanisms by suppressing TSH, the NF-κB/TNF-α pathway, iNOS, lipid peroxidation, Ki-67, and inflammatory mediators. On the other hand, they improved THs, antioxidant parameters, and the Nrf2/HO-1 pathway. HES and ELT exhibited an ameliorative effect that was reflected in the histopathological, immunohistochemical, and ultrastructural results. These results indicate that HES is a pneumoprotective agent that could be a promising treatment for oxidative stress, inflammation, and proliferation.
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This study aims to investigate the effect of hydroethanolic extracts of Cynara scolymus (C. scolymus) leaf (CLHE) and C. scolymus flower (CFHE) on the hepatic histopathological lesions and functional biochemical changes induced by type 2 diabetes mellitus (T2DM). The rat model of T2DM was induced by intraperitoneal injection of streptozotocin (STZ) in a dose of 60 mg/kg for 15 minutes following nicotinamide (NA) (60 mg/kg). The rats were allocated into four groups: group 1 (negative control), group 2 (diabetic control), group 3 (diabetic rats supplemented with 100 mg/kg/day CLHE), and group 4 (diabetic rats supplemented with 100 mg/kg/day CFHE). Treatment with CLHE and CFHE, for the study duration of 28 days, significantly improved the deteriorated hepatic glycogen content, glycogen phosphorylase, glucose-6-phosphatase activities, serum fructosamine levels, lipid profile, aspartate transaminase activities, and alanine transaminase activities as well as serum insulin and C-peptide levels. The elevated liver lipid peroxidation and the decreased activities of superoxide dismutase and glutathione peroxidase were significantly alleviated. The elevated expression of the proinflammatory cytokine tumor necrosis factor-α in the liver of diabetic rats was significantly reduced by treatments with CLHE and CFHE. NA/STZ-induced T2DM exhibited hepatic histopathological changes in the form of disordered hepatocytes, cytoplasm dissolution, and mononuclear leukocytic infiltration. The electron microscopic ultrastructure study revealed damaged mitochondria with ill-defined cristae and fragmentation of the rough endoplasmic reticulum. Treatments with CLHE and CFHE remarkably amended these histopathological and EM ultrastructural changes. In conclusion, both CLHE and CFHE may have antidiabetic and improvement effects on the liver function and structural integrity, which may be mediated, at least in part, via suppression of inflammation and oxidative stress and enhancement of the antioxidant defence system.
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Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.
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Injúria Renal Aguda , Fator de Transcrição AP-1 , Ratos , Animais , Vildagliptina , Solução Salina , Injúria Renal Aguda/etiologia , Fígado/metabolismo , Macrófagos/metabolismoRESUMO
We investigated the protective effect of green tea on diabetic hepato-renal complications. Thirty male Wistar rats were randomly divided into five equal groups: normal control, diabetic control, glibenclamide-treated, green tea-treated, and combined therapy-treated groups; ethical approval number "BERC-014-01-20." After eight weeks, animals were sacrificed by CO2 euthanasia method, liver and kidney tissues were processed and stained for pathological changes, and blood samples were collected for biochemical analysis. Diabetic rats showed multiple hepato-renal morphological and apoptotic changes associated with significantly increased some biochemical parameters, while serum albumin and HDL decreased significantly compared to normal control (p < .05). Monotherapy can induce significant improvements in pathological and biochemical changes but has not been able to achieve normal patterns. In conclusion, green tea alone has a poor hypoglycaemic effect but can reduce diabetic complications, whereas glibenclamide cannot prevent diabetic complications. The addition of green tea to oral hypoglycaemic therapy has shown a potent synergistic effect.
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Complicações do Diabetes , Diabetes Mellitus Experimental , Ratos , Masculino , Animais , Chá , Ratos Wistar , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Glibureto/farmacologia , Glibureto/uso terapêutico , FígadoRESUMO
Background: Cerebral venous sinus thrombosis (CVST) secondary to nephrotic syndrome (NS) is rarely reported. Additionally, treating steroid-sensitive nephrotic syndrome (SSNS) that changes to steroid resistance (SRNS) is difficult, with many relapses and side effects. Case presentation: A 32-month-old SSNS male child turned into SRNS and developed cerebral venous sinus thrombosis (CVST), a rare complication of NS. As a result of the administration of combined pulse methylprednisolone and IV Rituximab (RTX) therapy, the patient showed marked improvement, the results of urine analysis were remarkably improved, and the child started to respond to treatment. Conclusion: Successful treatment of a rare case of juvenile SSNS behaving as SRNS with the development of CVST could be established using combined steroid pulse therapy, Enoxaparin, and the B lymphocytes monoclonal antibodies RTX.
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Background: Cadmium (Cd) is a toxic heavy metal used in many industries. Since the second half of the 20th century, legislation on Cd use was put to limit the exponential rise in its environmental levels. This study aimed to investigate Cd's functional and ultrastructural changes on rats' reproductive systems and the role of Zingiber officinale (Ginger) in protecting against Cd-induced toxicity. Methods: Thirty adult male albino rats were randomly assigned into three equal groups (n = 10); control, Cd-exposed/untreated, and Cd-exposed/Gin-treated. Rat testes were weighed, and testicular tissue sections were examined under the electron microscope. Semen analysis, morphological examination of spermatozoa, and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. In addition, testicular tissue homogenates were analyzed for malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) levels. Results: Cd-induced significant reduction in the mean testicular weight and GSH levels and plasma testosterone, LH and FSH levels with a concomitant increase in testicular MDA and NO levels. There was also a deterioration in semen analysis parameters and spermatozoa morphology, with testicular structural damage in the form of architecture distortion and necrosis of seminiferous tubules and testicular interstitial cells. Daily administration of ginger for 4 weeks protected against CD-induced toxicity, preserving tissue architecture, improved plasma levels of testosterone, LH and FSH and testicular levels of GSH, and reduced testicular levels of MDA, NO. Conclusion: Ginger has a protective effect on Cd-induced deterioration of testicular tissue's structural and functional integrity by improving testicular tissue antioxidant capacity and steroid production, which ameliorates sex hormone levels in the blood.
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Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6â mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Colecalciferol/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Suplementos Nutricionais , Glibureto/farmacologia , Glibureto/uso terapêutico , Ratos , Ratos Wistar , Inibidores do Fator de Necrose Tumoral , Vitaminas/farmacologia , Vitaminas/uso terapêuticoRESUMO
Peptic ulcer is a widespread disease, with a lifetime frequency of 5−10% among the general population and an annual incidence of 0.1−0.3%. Ovothiol A is naturally produced from sea urchin eggs with special antioxidant activity. Gastric ulcers were induced in rats by a single ethanol dose (5 mL/kg). The rats were divided into control, ulcer, and ulcer with 250 and 500 mg/kg ovothiol A doses. Molecular docking studies were used to examine the interactions between ovothiol A and the H+/K+ ATPase active site residues. Ovothiol A led to a significant decline (p < 0.05) in gastric juice volume, ulcer index, MDA, IL-6, and cytochrome c, while levels of gastric juice pH, GSH, CAT, GST, SOD, and NO increased. Histopathological investigation of stomach sections revealed architecture preservation of the gastric mucosa after ovothiol A administration. The anti-ulcerogenic activity of ovothiol A includes scavenging free radicals, inhibition of inflammation, regulation of apoptosis, and stabilization of fibroblast growth factors to promote gastric ulcers healing.
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Antiulcerosos , Úlcera Gástrica , Humanos , Ratos , Animais , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Etanol/metabolismo , Simulação de Acoplamento Molecular , Antiulcerosos/efeitos adversos , Superóxido Dismutase/metabolismo , Mucosa Gástrica/metabolismo , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Fibromyalgia (FM) is characterized by musculoskeletal pain, fatigue, sleep and memory disturbance. There is no definitive cure yet for FM-related health problems. Peroxisome proliferator-activated receptor's (PPAR's) activation is associated with insulin sensitisation and improved glucose metabolism. PPAR-γ was reported to alleviate FM allodynia. Limited data are discussing its effect on motor disorders. OBJECTIVE: To investigate the potential effect of PPAR-γ agonists (pioglitazone, as one member of thiazolidinediones (TZD)) on motor dysfunction in reserpine-induced FM in a rat model. MATERIALS AND METHODS: Thirty-six male Wistar rats were divided into negative control (n = 9) and reserpine-induced FM (n = 27) groups. The latter was subdivided into three equal subgroups (n = 9), positive control (untreated FM model), pioglitazone-treated and GW9662-treated. We evaluated muscle functions and activity of chloramphenicol acetyltransferase, superoxide dismutase, malondialdehyde, and serum levels of interleukin-8 and monocyte chemoattractant protein-1. RESULTS: Pioglitazone significantly relieved fatigue, improved muscle performance, reduced inflammatory cytokines and enhanced antioxidant's activity, while GW9662, a known PPAR-γ antagonist, aggravated the FM manifestations in the rat model. CONCLUSION: PPAR-γ agonists show a promising role against FM-associated motor dysfunctions.
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Fibromialgia/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Pioglitazona/uso terapêutico , Reserpina/farmacologia , Tiazolidinedionas/farmacologia , Animais , Fadiga , Fibromialgia/induzido quimicamente , Humanos , Masculino , PPAR gama , Ratos , Ratos WistarRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is associated with joint damage. For treatment, non-steroidal anti-inflammatory drugs (NSAIDs), steroidal agents, and immune-suppressants are used. Their side-effects require a safe and effective natural alternative. ANIMALS AND METHODS: Thirty-six male albino rats, half kept under observation for 1 week (group I) and others for 2 weeks (group II) were used. Each group was subdivided into: normal (A), RA (B), and oral mandarin-peel extract (MPE) treated (C). Ankle diameter, serum levels of RF, interleukin (IL)-1ß, TNFα, IL-4, IL-10, liver homogenates malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) were measured together with the histopathological examination. RESULTS: MPE treatment was associated with increased serum IL-4, IL-10, liver homogenates GSH, and SOD, and decreased ankle diameter, serum RF, IL-1ß, TNFα, liver homogenates MDA, NO, inflammatory cell infiltrate, and necrosis. Two weeks' treatment was better. CONCLUSIONS: MPE has useful effects in alleviating the disturbed ankle diameter, serum pro- and anti-inflammatory mediators, oxidative stress, and ankle joint histopathology in rheumatic rats.
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Antioxidantes/farmacologia , Artrite Experimental/tratamento farmacológico , Biomarcadores/análise , Citrus/química , Frutas/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Artrite Experimental/metabolismo , Citocinas/metabolismo , Masculino , RatosRESUMO
BACKGROUND: Pre-eclampsia poses a significant potential risk of hypertensive disorders during pregnancy, a leading cause of maternal deaths. Hyperuricemia is associated with adverse effects on endothelial function, normal cellular metabolism, and platelet aggregation and adhesion. This study was designed to compare serum urate levels in normotensive pregnant women to those with pregnancy-induced hypertension, and to evaluate its value as a potential predictive marker of hypertension severity during pregnancy. METHODS: A prospective, observational, case-control study conducted on 100 pregnant women in their third trimester. Pregnant women were classified into two groups (n=50) according to arterial blood pressure measurements: group I had normal blood pressure, and group II had a blood pressure of ≥ 140/90, which was further subdivided according to hypertension severity into IIa (pregnancy- induced hypertension, IIb (mild pre-eclampsia), and IIc (severe pre-eclampsia). Blood samples were obtained on admission. Serum urate, high sensitive C-reactive protein, and interleukin-1ß levels, and lipid profile were compared among the groups. RESULTS: A significant increase in the mean values of serum urate, C-reactive protein, and interleukin- 1ß levels was detected in gestational hypertensives. In addition, there was a positive correlation between serum urate levels and C-reactive protein and interleukin-1ß, as well as between serum urate levels and hypertension severity. CONCLUSION: Hyperuricemia and increased C-reactive protein and interleukin-1ß serum levels correlate with the severity of pregnancy-induced hypertension, and these biomarkers may play a role in the pathogenesis of pre-eclampsia. Serum urate measurement is sensitive, reliable markers that correlate well with the severity of hypertension in pregnant females with pre-eclampsia.