RESUMO
Global aflatoxin contamination of agricultural commodities is of the most concern in food safety and quality. This study investigated the hepatoprotective effect of 80% methanolic leaf extract of Annona senegalensis against aflatoxin B1 (AFB1)-induced toxicity in rats. A. senegalensis has shown to inhibit genotoxicity of aflatoxin B1 in vitro. The rats were divided into six groups including untreated control, aflatoxin B1 only (negative control); curcumin (positive control; 10 mg/kg); and three groups receiving different doses (100 mg/kg, 200 mg/kg, and 300 mg/kg) of A. senegalensis extract. The rats received treatment (with the exception of untreated group) for 7 days prior to intoxication with aflatoxin B1. Serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were measured. Hepatic tissues were analysed for histological alterations. Administration of A. senegalensis extract demonstrated hepatoprotective effects against aflatoxin B1-induced toxicity in vivo by significantly reducing the level of serum aspartate aminotransferase and alanine aminotransferase and regenerating the hepatocytes. No significant changes were observed in the levels of alkaline phosphatase, lactate dehydrogenase, and creatinine for the AFB1 intoxicated group, curcumin+AFB1 and Annona senegalensis leaf extract (ASLE)+AFB1 (100 mg/kg, 200 mg/kg, and 300 mg/kg body weight [b.w.]) treated groups. Annona senegalensis is a good candidate for hepatoprotective agents and thus its use in traditional medicine may at least in part be justified.Contribution: The plant extract investigated in this study can be used in animal health to protect the organism from toxicity caused by mycotoxins.
Assuntos
Annona , Curcumina , Ratos , Animais , Aflatoxina B1/toxicidade , Curcumina/farmacologia , Alanina Transaminase/farmacologia , Fosfatase Alcalina/farmacologia , Creatinina/farmacologia , Fígado , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Aspartato Aminotransferases/farmacologia , Lactato DesidrogenasesRESUMO
OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Criança , Humanos , Adolescente , Tenofovir/efeitos adversos , Creatinina/farmacologia , Creatinina/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos Prospectivos , Ácido Úrico/farmacologia , Ácido Úrico/uso terapêutico , Infecções por HIV/tratamento farmacológico , Proteinúria , Taxa de Filtração Glomerular , Fosfatos/uso terapêutico , Glucose/farmacologia , Glucose/uso terapêuticoRESUMO
High dose of fluoride intake is associated with toxic effects on kidney and cardiac tissues. This study evaluated the potential protective effect of fermented rooibos tea (RTE) on sodium fluoride (NaF)-induced cardiorenal toxicity in rats. Male Wistar rats (n = 56) were randomly allocated into one of seven equal groups: control, NaF (100 mg/kg orally), NaF + RTE (2%, w/v), NaF + RTE (4%, w/v), NaF + lisinopril (10 mg/kg orally), 2% RTE, and 4% RTE. The experiment lasted for 14 days and RTE was administered to the rats as their sole source of drinking fluid. NaF induced cardiorenal toxicity indicated by elevated level of urea, creatinine, LDH, creatinine kinase-MB, and cardiac troponin I in the serum, accompanied by altered histopathology of the kidney and heart. Furthermore, levels of H2O2, malondialdehyde, and NO were elevated, while GSH level was depleted in the kidney and heart due to NaF intoxication. Protein levels of c-reactive protein, TNFα, IL-1B, and NF-κB were increased by NaF in the serum, kidney, and heart. RTE at 2% and 4% (w/v) reversed cardiorenal toxicity, resolved histopathological impairment, attenuated oxidative stress and inhibited formation of pro-inflammatory markers. RTE at both concentrations down-regulates the mRNA expression of NF-κB, and upregulates the mRNA expression of both IκB and IκKB, thus blocking the activation of NF-κB signaling pathway. Taken together, these results clearly suggest that the protective potential of rooibos tea against NaF-induced cardiorenal toxicity, oxidative stress, and inflammation may be associated with the modulation of the NF-κB signaling pathway.
Assuntos
Aspalathus , Fluoreto de Sódio , Ratos , Masculino , Animais , Ratos Wistar , NF-kappa B/metabolismo , Aspalathus/metabolismo , Creatinina/farmacologia , Peróxido de Hidrogênio , Estresse Oxidativo , Transdução de Sinais , Inflamação/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , CháRESUMO
Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.
Assuntos
Lactação , Leite , Feminino , Bovinos , Animais , Leite/metabolismo , Creatinina/análise , Creatinina/metabolismo , Creatinina/farmacologia , Dieta/veterinária , Temperatura Alta , Suplementos Nutricionais/análise , Resposta ao Choque Térmico , Vitamina E , Carnitina/metabolismo , Alanina/análise , Alanina/metabolismo , Alanina/farmacologia , Aminoácidos/metabolismo , Vitamina D/metabolismoRESUMO
BACKGROUND: The objective of this study was to examine and analyze differential methylation profiles in order to investigate the influence of hyper-methioninemia (HM) on the development of diabetic nephropathy (DN). Male Wistar rats, aged eight weeks and weighing 250-300 g, were randomly assigned into four groups: a control group (Healthy, n = 8), streptozocin-induced rats (STZ group, n = 8), HM + STZ group (n = 8), and the Tangshen Formula (TSF) treatment group (TSF group, n = 8). Blood glucose levels and other metabolic indicators were monitored before treatment and at four-week intervals until 12 weeks. Total DNA was extracted from the aforementioned groups, and DNA methylation landscapes were analyzed via reduced representative bisulfite sequencing. RESULTS: Both the STZ group and HM + STZ group exhibited increased blood glucose levels and urinary albumin/creatinine ratios in comparison with the control group. Notably, the HM + STZ group exhibited a markedly elevated urinary albumin/creatinine ratio (411.90 ± 88.86 mg/g) compared to the STZ group (238.41 ± 62.52 mg/g). TSF-treated rats demonstrated substantial reductions in both blood glucose levels and urinary albumin/creatinine ratios in comparison with the HM + STZ group. In-depth analysis of DNA methylation profiles revealed 797 genes with potential therapeutic effects related to TSF, among which approximately 2.3% had been previously reported as homologous genes. CONCLUSION: While HM exacerbates DN through altered methylation patterns at specific CpG sites, TSF holds promise as a viable treatment for DN by restoring abnormal methylation levels. The identification of specific genes provides valuable insights into the underlying mechanisms of DN pathogenesis and offers potential therapeutic targets for further investigation.
Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Ratos , Masculino , Animais , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Glicemia , Metionina/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Creatinina/metabolismo , Creatinina/farmacologia , Creatinina/uso terapêutico , Ratos Wistar , Metilação de DNA , Rim/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacologia , Albuminas/metabolismoRESUMO
Investigation the protective effect of transient receptor potential channel modulator 2-Aminoethoxydiphenyl Borate (2-APB) on aminoglycoside nephrotoxicity caused by reactive oxygen species, calcium-induced apoptosis and inflammation was aimed. Forty Wistar rats were divided (n=8) as follows: Control group; DMSO group; 2-APB group; Gentamicin group (injected 100 mg/kg gentamicin intramuscularly for 10 days); Gentamicin+ 2-APB group (injected 2 mg/kg 2-APB intraperitoneally, then after 30 minutes 100 mg/kg gentamicin was injected intramuscularly for 10 days). Blood samples were collected for biochemical analyses, kidney tissue samples were collected for light, electron microscopic and immunohistochemical investigations. In gentamicin group glomerular degeneration, tubular dilatation, vacuolization, desquamation of tubular cells and hyaline cast formation in luminal space and leukocyte infiltration were seen. Disorganization of microvilli of tubular cells, apical cytoplasmic blebbing, lipid accumulation, myelin figure like structure formation, increased lysosomes, mitochondrial swelling and disorganization of cristae structures, apoptotic changes and widening of intercellular space were found. TNF-α, IL-6 and caspase 3 expressions were increased. BUN and creatinine concentrations were increased. Increase in MDA levels and decrease in SOD activities were determined. Even though degeneration still continues in gentamicin+2-APB treatment group, severity and the area it occupied were decreased and the glomerular and tubule structures were generally preserved. TNF-α, IL-6, caspase 3 immunoreactivities and BUN, creatinine, MDA concentrations were reduced and SOD activities were increased markedly compared to gentamicin group. In conclusion, it has been considered that 2-APB can prevent gentamicin mediated nephrotoxicity with its anti-oxidant, anti-apoptotic and anti-inflammatory effects.
Assuntos
Nefropatias , Rim , Ratos , Animais , Caspase 3/metabolismo , Caspase 3/farmacologia , Aminoglicosídeos/efeitos adversos , Aminoglicosídeos/metabolismo , Ratos Wistar , Creatinina/metabolismo , Creatinina/farmacologia , Fator de Necrose Tumoral alfa , Interleucina-6 , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Antibacterianos/efeitos adversos , Antioxidantes/farmacologia , Gentamicinas/toxicidade , Gentamicinas/metabolismo , Superóxido Dismutase/metabolismo , Estresse OxidativoRESUMO
AIM: To investigate the mechanism by which NF-κB p65 activates miR-150 to suppress TRPC6 expression and promote renal ischemia-reperfusion injury. METHODS: To assess the transcription of miR-150, NF-B p65, and TRPC6 in HK-2 cells treated with hypoxia reperfusion and rat kidney tissue damaged by ischemia-reperfusion (I/R), qPCR was implemented. The protein production of NF-κB p65 and TRPC6 was assessed by Western blot (WB) analysis. The histological score of rat kidney tissue was assessed using H&E (hematoxylin and eosin) staining. To assess the rate of apoptosis of renal tissue cells following I/R injury, we used the TACS TdT In Situ Apoptosis Detection Kit. To find out the impairment of renal function, blood levels of creatinine (Cr) and blood urea nitrogen (BUN) were tested in rats. Concentrations of inflammatory cytokines, including IL-1ß, IL-10, and TNF-α, were detected in HK-2 cells and rat renal tissue cells utilizing ELISA kits. FITC and CCK-8 were employed to analyze the death rate and cellular proliferation of HK-2 cells. To analyse the mechanism of engagement between NF-κB p65 and the miR-150 promoter, coupled with the detrimental impact of miR-150 on TRPC6, we adopted the dual-luciferase reporter assay. To confirm the activating effect of NF-κB p65 on miR-150,we implemented the ChIP assay. RESULTS: NF-κB p65 expression was significantly upregulated in rat renal tissue following IRI. Applying the dual-luciferase reporter assay, we demonstrated that the specific attachment of NF-B p65 with the miR-150 promoter location is viable, resulting in the promotion of the activity of the promoter. When miR-150 was overexpressed, we observed a notable reduction in cell proliferation. And it notably increased the rate of cellular apoptosis rate and amounts of the proinflammatory cytokines IL-1ß, IL-10, and TNF-α. Employing the dual-luciferase reporter assay, we demonstrated that miR-150 transfection diminished the function of luciferase in the TRPC6-WT group, whereas luciferase activity in the TRPC6-MUT group remained unchanged, indicating that miR-150 is a targeted inhibitor of TRPC6. In the rat renal I/R model, when miR-150 was inhibited or TRPC6 was overexpressed in the rat kidney I/R model, the histological score of rat kidney tissue significantly decreased, so did the quantities of proinflammatory cytokines IL-1ß, IL-10, TNF-α, creatinine (Cr) and blood urea nitrogen (BUN) contents and the rate of cell apoptosis in kidney tissue. CONCLUSION: Activation of miR-150 by NF-κB p65 results in downregulation of TRPC6 expression and promotion of IRI in the kidney.
Assuntos
MicroRNAs , Traumatismo por Reperfusão , Ratos , Animais , NF-kappa B/metabolismo , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Canal de Cátion TRPC6/genética , Canal de Cátion TRPC6/metabolismo , Creatinina/farmacologia , Transdução de Sinais , Ratos Sprague-Dawley , Rim/patologia , Citocinas/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Luciferases/metabolismo , Luciferases/farmacologiaRESUMO
Uric acid nephropathy (UAN) is caused by purine metabolism disorders. UAN rat models were established in SD rats. The modeling rats received different doses of hispidulin (10, 20, 50 mg/mL). Febuxostat was applied as the positive drug. Serum creatinine, uric acid (UA), and cystatin-C (cys-C), neutrophil gelatinase-associated lipocalin (NGAL), IL-1ß, IL-8, TNF-α, and IL-6 in rats were detected. HE staining was done to assess kidney injury. UAN rats possessed prominent levels of serum creatinine, UA, cys-C, and NGAL, which all reduced after hispidulin treatment in a dose-dependent manner. HE staining determined the improvement of kidney injury after treatment, which was comparable to the efficacy of febuxostat. Hispidulin inhibited the release of IL-1ß, IL-8, TNF-α, and IL-6 in UAN rats. Hispidulin enhanced autophagy in UAN rats, presenting as ascending LC3II/I ratio and downregulated P62. The increasing trend of inflammasome-related proteins of NLRP3 and Caspase-1 was changeovered by hispidulin. The activation of NF-kB signaling was intercepted by hispidulin in UAN rats. Hispidulin can effectively improve renal function injury caused by UAN in rats. The mechanism may be related to the inhibition of inflammatory response induced by autophagy and activation of NF-κB pathway.
Assuntos
Flavonas , Nefropatias , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia , Lipocalina-2/efeitos adversos , Lipocalina-2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Interleucina-8/uso terapêutico , Creatinina/farmacologia , Creatinina/uso terapêutico , Febuxostat/efeitos adversos , Interleucina-6/metabolismo , Ratos Sprague-Dawley , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Transdução de SinaisRESUMO
AIM: The research intended to explore the possible nephroprotective potential of the ethyl acetate fraction derived from Acacia catechu leaves against nephrotoxicity brought about by 5-fluorouracil (5-FU) in Wistar rats. BACKGROUND: While possessing strong anticancer properties, 5-FU is hindered in its therapeutic application due to significant organ toxicity linked to elevated oxidative stress and inflammation. OBJECTIVE: The study is undertaken to conduct an analysis of the ethyl acetate fraction of A. catechu leaves both in terms of quality and quantity, examining its impact on different biochemical and histopathological parameters within the context of 5-FU-induced renal damage in rats and elucidation of the mechanism behind the observed outcomes. METHODOLOGY: Intraperitoneal injection of 5-FU at a dosage of 20 mg/kg/day over 5 days was given to induce nephrotoxicity in rats. The evaluation of nephrotoxicity involved quantifying serum creatinine, urea, uric acid, and electrolyte concentrations. Furthermore, superoxide dismutase, catalase antioxidant enzymes, and TNF-α concentration in serum were also measured. RESULTS: 5-FU injection led to the initiation of oxidative stress within the kidneys, leading to modifications in renal biomarkers (including serum creatinine, urea, uric acid, and Na+, K+ levels), and a reduction in antioxidant enzymes namely superoxide dismutase and catalase. Notably, the presence of the inflammatory cytokine TNF-α was significantly elevated due to 5-FU. Microscopic examination of renal tissue revealed tubular degeneration and congestion. However, treatment involving the ethyl acetate fraction derived from A. catechu leaves effectively and dose-dependently reversed the changes observed in renal biomarkers, renal antioxidant enzymes, inflammatory mediators, and histopathological features, bringing them closer to normal conditions. The observed recuperative impact was mainly attributed to the antioxidant and antiinflammatory properties of the fraction. CONCLUSION: The ethyl acetate fraction of A. catechu leaves exhibited a mitigating influence on the renal impairment caused by 5-FU, showcasing its potential as a nephroprotective agent capable of preventing and ameliorating 5-FU-induced nephrotoxicity.
Assuntos
Acacia , Antioxidantes , Ratos , Animais , Ratos Wistar , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catalase/metabolismo , Catalase/farmacologia , Acacia/metabolismo , Fluoruracila/toxicidade , Fluoruracila/metabolismo , Creatinina/metabolismo , Creatinina/farmacologia , Fator de Necrose Tumoral alfa , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia , Estresse Oxidativo , Rim , Inflamação/tratamento farmacológico , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Ureia/metabolismo , Ureia/farmacologia , BiomarcadoresRESUMO
Methyl tert-butyl ether (MTBE) is soluble in water and can contaminate water sources when it spills during transportation or leaks from underground storage tanks. Incomplete combustion releases MTBE as exhaust fumes that can be deposited on urban surfaces. Meanwhile, car tires erosion emits of large amounts of rubber dust (RP), easily transported to water bodies. Therefore, this study has the objective of assessing the toxicity of varying concentrations of MTBE (0, 2.5, 5.0 µL L-1) and RP (0, 5.0, 10.0 mg L-1 RP), both individually and in combination, over a period of 28 days on Nile tilapia (Oreochromis niloticus). MTBE and PR decreased fish growth performance. Blood biochemical analytes indicated that MTBE and RP led to increasing Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK), alkaline phosphatase and gamma-glutamyl transferase (GGT) activities. Alterations related to glucose, triglycerides, cholesterol, and creatinine, plasma contents, were also observed. Increased antioxidant biomarkers, including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), glutathione reductase (GR), and malondialdehyde (MDA), was observed. Exposure fish to MTBE and PR changed metabolic profile of muscle tissue. Moreover, results showed that MTBE, its metabolites, and PR could accumulate in the muscle tissue of fish. Results suggest that MTBE and RP can impact fish health, both individually and when combined. The presence of MTBE enhances the toxicity of RP, indicating a synergistic effect. Nevertheless, further studies are needed to understand the impact of toxic compounds on aquatic environments and organisms' health.
Assuntos
Ciclídeos , Animais , Ciclídeos/metabolismo , Pós/metabolismo , Pós/farmacologia , Borracha/toxicidade , Borracha/metabolismo , Estresse Oxidativo , Creatinina/metabolismo , Creatinina/farmacologia , Água/metabolismoRESUMO
INTRODUCTION: The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m2 [G1-G2 subcohort] and 30 to < 60 mL/min/1.73 m2 [G3 subcohort]). RESULTS: In total, 93 patients were evaluated (G1-G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (- 11.8 ± 10.8/- 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (- 12.9 ± 10.5/- 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, - 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1-G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L. CONCLUSION: Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug's efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination. CLINICAL TRIAL REGISTRATION: jRCTs031200273.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Creatinina/farmacologia , Creatinina/uso terapêutico , Estudos Prospectivos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Potássio/farmacologia , Potássio/uso terapêutico , Glucose/farmacologia , Glucose/uso terapêutico , Sódio/farmacologia , Sódio/uso terapêuticoRESUMO
Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.
Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ratos , Animais , Masculino , Nefropatias Diabéticas/tratamento farmacológico , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Estreptozocina/uso terapêutico , Creatinina/metabolismo , Creatinina/farmacologia , Peróxido de Hidrogênio/farmacologia , Diabetes Mellitus Experimental/metabolismo , Ratos Wistar , Rim/metabolismoRESUMO
Liver ischemia/reperfusion (IR) often affects distant organs, such as small intestine, kidney, and lung. Coriandrum sativum (CS) has an antioxidant and anti-inflammatory effect on liver damage. The aim of this study was to investigate the anti-inflammatory and antiapoptotic effects of CS extract on small intestine, lung, and kidney after the liver IR injury. Small intestine, lung, and kidney tissues were evaluated and scored in terms of cell degeneration, inflammation, and congestion, as well as caspase-3 (Cas-3) and cluster of differentiation 31 (CD31) immunostainings were carried out. Renal enzymes, creatinine and urea levels were measured biochemically in serum. After IR, a decrease in villi size, diffuse degeneration, epithelial cell shedding and extensive congestion in the capillaries were observed. Meanwhile, the number of degenerated villi and congestion decreased in the IR+CS group. Due to IR, increased congestion was detected in the interalveolar septum of the lungs and in the capillaries between the kidney tubules. It was also observed that the positively stained cells with Cas-3 and CD31 were increased in the lung, kidney, and small intestine tissues of the IR group, and decreased in the IR+CS group. Kidney enzymes, urea and creatinine levels were significantly increased in the IR group and decreased in the IR+CS group. In conclusion, it was observed that liver IR caused changes in distant organs, especially in the small intestine, lung, and kidneys. Damaging effects of IR as well as apoptosis and inflammation were found to be decreased in the groups treated with CS.
Assuntos
Coriandrum , Hepatopatias , Traumatismo por Reperfusão , Humanos , Creatinina/farmacologia , Creatinina/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Fígado/irrigação sanguínea , Rim/irrigação sanguínea , Inflamação/complicações , Isquemia , Apoptose , Ureia/farmacologia , Ureia/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Transplantation is the most effective treatment for end-stage chronic kidney disease, as this procedure prolongs and improves the patient's quality of life. One of the key problems is the risk of graft rejection. The purpose of this research was to identify and analyse prognostic factors that will prevent rejection. In particular, the prognostic factors grouped by methods of synthesis, generalisation and statistical processing with calculation and graphical representation of hazard ratio and correlation coefficient were grouped, namely: age of donor and recipient, time of cold kidney ischaemia, duration of preoperative dialysis, body mass index, presence of concomitant diseases (diabetes mellitus, hypertension), primary causes causing transplantation. Several molecular genetic and biochemical prognostic markers (transcription factors, immunocompetent cell signalling and receptors, cytostatin C, creatinine, citrate, lactate, etc.) are annotated. It has been demonstrated that creatinine reduction rate determines the risk of rejection, displaying the dynamics of cystatin C and creatinine changes in the postoperative period. Young recipients who underwent prolonged preoperative dialysis were identified as having the highest risk of rejection. Diabetes and hypertension bear a non-critical but commensurately equal risk of rejection. The survival rate of the graft is better when transplanted from a living donor than from a deceased donor. A correlation between cold ischaemia time, body mass index and the probability of graft failure has been proven, namely, the greater the donor and recipient body mass index and the longer the cold ischaemia time, the lower the chance of successful long-term organ acclimation. The data obtained can be used as prognostic factors for graft accommodation at different intervals after surgery.
Assuntos
Hipertensão , Falência Renal Crônica , Transplante de Rim , Humanos , Prognóstico , Creatinina/farmacologia , Qualidade de Vida , Rim , Sobrevivência de Enxerto , Doadores Vivos , Fatores de Risco , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Methotrexate (MTX), a cytotoxic chemotherapeutic and immunosuppressant agent, is widely used in the treatment of autoimmune diseases and different types of cancers. However, its use has been limited by its life-threatening side effects, including nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the protective effect of sitagliptin on methotrexate (MTX)-induced nephrotoxicity in rats. Twenty-four rats were divided into four groups: control group, which received the vehicle for 6 days; MTX group, which received a single dose of MTX, followed by five daily doses of vehicle dosing; MTX + sitagliptin group, which received a single dose of MTX 1 h after the first sitagliptin treatment and six daily doses of sitagliptin; and sitagliptin group, which received sitagliptin for 6 days. Both MTX and sitagliptin were given as intraperitoneal injections at a dose of 20 mg/kg body weight. All rats were euthanized on the seventh day of the study. Kidney tissues were harvested and blood samples were collected. Serum levels of blood urea nitrogen (BUN) and creatinine were evaluated. Furthermore, catalase, glutathione peroxidase, superoxide dismutase activities, and malondialdehyde (MDA) levels were determined in kidney tissue. In addition, histopathological analysis was conducted. Histopathological evaluation showed that MTX-induced marked kidney injury. Biochemical analysis revealed a significant increase of BUN and creatinine in the serum of the MTX group. Furthermore, oxidative stress and depressed antioxidant system of the kidney tissues were evident in the MTX group. Sitagliptin did not affect these endpoints when administered alone, but it significantly attenuated the observed MTX-induced effects. These results suggest that sitagliptin exhibits potent anti-oxidant properties against the nephrotoxicity induced by MTX in rats.
Assuntos
Metotrexato , Insuficiência Renal , Ratos , Animais , Metotrexato/toxicidade , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/farmacologia , Creatinina/farmacologia , Antioxidantes , Rim/patologia , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologiaRESUMO
Chromium (Cr) is an environmental pollutant, has high redox potential, and can exist in various oxidation states, possibly leading to nephrotoxicity. As a potential treatment option, Fagonia indica (F. indica) is an herb remedy traditionally used as a phytomedicine to cure ailments. However, efficient validation of its protective effect and molecular mechanisms has not yet been established. As such, this study aims to investigate the protective effect of F. indica against Cr-induced nephrotoxicity in Swiss mice. Mice were divided into five groups: group I (negative control), group II (F. indica), group III (potassium dichromate [PDC]-treated), group IV (PDC + saline), and group V (PDC + F. indica). Our results demonstrate that group III exhibited decreases in superoxide dismutase (SOD), glutathione s-transferases (GST), glutathione peroxidase (GSH-Px), catalase (CAT), and thioredoxin peroxidase (TPX) levels. Meanwhile, protein carbonyl (PCO) and malondialdehyde (MDA) levels increased in kidney homogenates, increasing the expression of the pro-inflammatory cytokine interleukin-6 (IL-6). This was followed by elevated NF-κB, blood urea nitrogen (BUN), and creatinine serum levels in group III compared with group I. Moreover, histopathological and immunohistochemical examinations demonstrated severe damage to the renal tubular epithelial cells, as well as marked congestion and expressions of caspase-3 and NF-κB. Further, group V showed an improvement in antioxidant activity parameters and reductions in the IL-6, caspase-3, and NF-κB expressions, followed by significant decreases in NF-κB, BUN, and creatinine serum levels. Furthermore, fewer histopathological disturbances were observed compared with untreated group III. Such alterations may be attributed to the antioxidant and anti-inflammatory effects of F. indica. Therefore, our exploration reveals that F. indica is effective in protecting against Cr-induced nephrotoxicity, and it could be applied in the future to human kidney diseases caused by environmental pollutants.
Assuntos
Antioxidantes , Citocinas , Ratos , Humanos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Caspase 3 , Citocinas/metabolismo , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Interleucina-6/metabolismo , Interleucina-6/farmacologia , Creatinina/farmacologia , Ratos Wistar , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologiaRESUMO
Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kgâ¢day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kgâ¢day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kgâ¢day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.
Assuntos
Anti-Infecciosos , Transtornos do Metabolismo dos Lipídeos , Triclosan , Animais , Óleo de Milho/metabolismo , Óleo de Milho/farmacologia , Creatinina/metabolismo , Creatinina/farmacologia , Citocinas/metabolismo , Citocinas/farmacologia , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Ácidos Graxos/metabolismo , Fibrose , Rim/metabolismo , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitrogênio/metabolismo , Triclosan/toxicidade , Ureia , Ácido Úrico/metabolismo , Ácido Úrico/farmacologiaRESUMO
Amikacin (AK) is an aminoglycoside that is widely used to treat life-threatening Gram-negative infections, especially in intensive care units. Despite its wide clinical indications, AK causes serious side effects such as kidney toxicity. AK was found to lead to tissue damage primarily through apoptosis and oxidative stress. Therefore, it was investigated whether misoprostol (MP), which has antioxidant and antiapoptotic properties, had a beneficial effect on kidney damage caused by AK. It was observed that kidney injury molecule-1 (KIM-1) mRNA, blood urea nitrogen (BUN), creatinine (Cr), NADPH oxidase-4 (NOX-4) and Caspase-3 (CAS-3) levels increased in the AK-treated group in comparison with the control group, while uric acid, albumin, and total protein levels were decreased. In rats that were treated with AK+MP, the levels of KIM-1 mRNA, BUN, Cr, NOX-4 and CAS-3 were significantly decreased in comparison with the AK group, while uric acid, albumin and total protein levels increased. According to the obtained results, MP was found to be quite effective in the protection of kidneys from the toxic effects of AK.
Assuntos
Amicacina , Misoprostol , Ratos , Animais , Amicacina/toxicidade , Amicacina/metabolismo , Misoprostol/metabolismo , Misoprostol/farmacologia , Alprostadil/farmacologia , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia , Antibacterianos/efeitos adversos , Rim/metabolismo , Estresse Oxidativo , Creatinina/metabolismo , Creatinina/farmacologiaRESUMO
OBJECTIVE: Even though oxidative and inflammatory bursts are a big part of renal reperfusion injury (RI/R), Pistia stratiotes (PS) has been used for a long time to stop these overreactions. People have said that it can drop both blood sugar and cholesterol. Hence, the goal of this study was to show how PS changed kidney reperfusion damage in both diabetic and normal rats. MATERIALS AND METHODS: In the study, 30 min of renal ischemia (RI) was followed by 1 h of recovery for each rat. Before the test, PS (100 mg/kg p. o.) was given to the animals for 7 days. Then, using the mixture from the separated kidney tissues, the antioxidant, inflammation, and histopathological effects were determined. RESULTS: When compared to RI/R, diabetic rats given PS had lower blood sugar, aspartate aminotransferase, blood urea nitrogen, and creatinine, myeloperoxidase, C-reactive protein, and tumor necrosis factor-alpha levels in their urine. CONCLUSION: PS potentially worked in hyperglycemic rats protecting them against RI/R. It is possible that PS's ability to protect the kidneys of the test rats is due to its ability to fight free radicals, lower blood sugar, and stop inflammation.
Assuntos
Araceae , Diabetes Mellitus Experimental , Nefropatias , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Glicemia/metabolismo , Rim , Nefropatias/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Inflamação/metabolismo , Inflamação/patologia , Estresse Oxidativo , Creatinina/metabolismo , Creatinina/farmacologiaRESUMO
OBJECTIVE: The aim: To determine whether Tilianin (TIL) may have Nephroprotective effects on bilateral renal IRI in rats by analyzing kidney function biomarkers U and Cr, inflammatory cytokines like TNF α and IL-1ß, antioxidant marker total anti-oxidant Capacity (TAC), anti-apoptotic markers caspase-3, and histopathological scores. PATIENTS AND METHODS: Materials and methods: 20 rats divided into even 4 groups as: Sham group: Rats underwent median laparotomies without having their ischemia induced. Control group: Rats had bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion. Vehicle group: 30 minutes prior to the onset of ischemia, rats were given a pretreatment of corn oil and DMSO. Tilianin treated group: Rats administered Tilianin 5 mg/kg for 30 min prior to ischemia induction, then IRI. RESULTS: Results: The study found that the serum levels of TNF, IL-1, caspase-3, urea and creatinine, as well as TNF and creatinine in the Tilianin group were significantly lower than those of the control and vehicle groups. On the other hand, it revealed that TAC levels are remarkably higher in the Tilianin group than they are in the control and vehicle groups. CONCLUSION: Conclusions: This study concluded that Tilianin have a Nephroprotective effect via multiple impacts as anti-inflammatory, anti-apoptotic, and anti-oxidant agents.