RESUMO
Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg/kg body weight (b.w.)/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg/kg b.w./day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg/kg b.w./day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman-Keul's test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K/AKT signaling pathways.
Assuntos
Celastrus/química , Rim/efeitos dos fármacos , Rim/metabolismo , Compostos Organometálicos/efeitos adversos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Feminino , Expressão Gênica , Imuno-Histoquímica , Rim/patologia , Rim/ultraestrutura , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacosRESUMO
Hypertensive-induced renal damage (HRD) is an important public health and socioeconomic problem worldwide. The herb pair Radix Astragali- (RA-) Radix Salviae Miltiorrhizae (RS) is a common prescribed herbal formula for the treatment of HRD. However, the underlying mechanisms are unclear. The purpose of our study is to explore the mechanism of combination of Radix Astragali (RA) and Radix Salviae Miltiorrhizae (RS) ameliorating HRD by regulation of the renal sympathetic nerve. Thirty 24-week-old spontaneously hypertensive rats (SHRs) as the experimental group were randomly divided into the RA group, the RS group, the RA+RS group, the valsartan group, and the SHR group and six age-matched Wistar Kyoto rats (WKY) as the control group. After 4 weeks of corresponding drug administration, venipuncture was done to collect blood and prepare serum for analysis. A color Doppler ultrasound diagnostic instrument was used to observe renal hemodynamics. Enzyme-linked immunosorbent assay was used to detect norepinephrine (NE), epinephrine (E), angiotensin II (Ang II), and B-type brain natriuretic peptide (BNP). Simultaneously, the kidneys were removed immediately and observed under a transmission electron microscope to observe the ultrastructural changes. And the concentration of transforming growth factor-ß1 (TGF-ß1), angiotensin type 1 receptor (AT1), and nitric oxide (NO) was detected by immunohistochemistry. Our results showed that renal ultrasonography of rats showed no significant difference in renal size among groups. The RA+RS group had obviously decreased vascular resistance index. The levels of NE, E, BNP, Ang II, AT1, and TGF-ß1 were decreased (P < 0.05), and the density of NO was increased. Pathological damage of the kidney was alleviated. In conclusion, the results of the present study suggested sympathetic overexpression in the pathogenesis of HRD. The combination of RA and RS may inhibit the hyperexcitability of sympathetic nerves and maintain the normal physiological structure and function of kidney tissue and has a protective effect on the cardiovascular system.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Rim/patologia , Salvia miltiorrhiza/química , Animais , Astragalus propinquus , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/farmacologia , Hemodinâmica/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/fisiopatologia , Rim/diagnóstico por imagem , Rim/fisiopatologia , Rim/ultraestrutura , Masculino , Modelos Biológicos , Óxido Nítrico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Resistência Vascular/efeitos dos fármacosRESUMO
QiDiTangShen granules (QDTS), a traditional Chinese herbal medicine, have been used in clinical practice for treating diabetic kidney disease for several years. In our previous study, we have demonstrated that QDTS displayed good efï¬cacy on reducing proteinuria in mice with diabetic nephropathy (DN). However, the exact mechanism by which QDTS exerts its reno-protection remains largely unknown. To ascertain whether QDTS could target the gut microbiota-bile acid axis, the db/db mice were adopted as a mouse model of DN. After a 12-week of treatment, we found that QDTS significantly reduced urinary albumin excretion (UAE), and attenuated the pathological injuries of kidney in the db/db mice, while the body weight and blood glucose levels of those mice were not affected. In addition, we found that QDTS significantly altered the gut microbiota composition, and decreased serum levels of total bile acid (TBA) and BA profiles such as ß-muricholic acid (ß-MCA), taurocholic acid (TCA), tauro ß-muricholic acid (Tß-MCA) and deoxycholic acid (DCA). These BAs are associated with the activation of farnesoid X receptor (FXR), which is highly expressed in kidney. However, there was no significant difference between QDTS-treated and -untreated db/db mice regarding the renal expression of FXR, indicating that other mechanisms may be involved. Conclusively, our study revealed that QDTS significantly alleviated renal injuries in mice with DN. The gut microbiota-bile acid axis may be an important target for the reno-protection of QDTS in DN, but the specific mechanism merits further study.
Assuntos
Ácidos e Sais Biliares/sangue , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/microbiologia , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Disbiose , Fezes/microbiologia , Intestinos/microbiologia , Intestinos/patologia , Rim/metabolismo , Rim/ultraestrutura , Masculino , Proteinúria/sangue , Proteinúria/microbiologia , Proteinúria/prevenção & controleRESUMO
Renal fibrosis is a kind of progressive kidney disease leading to end-stage renal damage. Epithelial-mesenchymal transition (EMT) is one of the crucial features of renal fibrosis. Salvianolic acid B (SalB), isolated from traditional Chinese medicine Radix Salviae miltiorrhizae, has been proved to be suitable for renal protection. The aims of this study are to investigate the pharmacological effects of SalB on renal fibrosis and explore the underlying mechanisms. In vivo, our study showed that SalB could improve kidney dysfunction and reduce the expression of EMT-related proteins, including fibronectin (FN), α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß). In addition, SalB activated autophagy and up-regulated the expression of Sirt1. In vitro, our study showed that SalB reversed EMT in TGF-ß1-induced human kidney proximal tubular epithelial cells (HK-2 cells). Further mechanism studies showed that the inhibition of Sirt1 and autophagy could reverse the protective effect of SalB on the EMT process in TGF-ß1-induced HK-2 cells. Taken together, this study demonstrated that SalB attenuates EMT in the process of renal fibrosis through activating Sirt1-mediated autophagy, and Sirt1 could be a key target for treatment of renal fibrosis.
Assuntos
Autofagia/efeitos dos fármacos , Benzofuranos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Sirtuína 1/metabolismo , Actinas/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Fibronectinas/metabolismo , Fibrose , Humanos , Rim/enzimologia , Rim/ultraestrutura , Nefropatias/enzimologia , Nefropatias/patologia , Masculino , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismoRESUMO
Black phosphorus nanosheets (BPNSs) have been actively employed as nanomedicine agents for photothermal and photodynamic therapy by virtue of their unique optical properties. However, their chemical reactivity as a competent biomaterial has not been fully explored yet. Here, we report on the use of BPNSs as reactive oxygen species (ROS) scavengers to cure acute kidney injury (AKI) in mice. Importantly, in vivo analysis in mice revealed that BPNSs were preferably accumulated in kidney. We found that BPNSs alleviated oxidative-pressure-induced cellular apoptosis. In a ROS-triggered acute kidney injury (AKI) model, BPNSs effectively consumed ROS in kidney, demonstrating high efficacy for curing AKI. BPNSs also exhibited excellent biocompatibility and biodegradability, making them promising candidates for therapeutic treatment of AKI and other renal diseases.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Nanoestruturas/química , Fósforo/farmacologia , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/ultraestrutura , Camundongos , Fósforo/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: ShenYanXiaoBai granules is a traditional Chinese herbal medicine, It is used widely for the treatment of proteinuria caused by various kidney diseases. AIM OF THE STUDY: This study investigated the mechanism of Shenyan Xiaobai Granule in the treatment of nephritis proteinuria. MATERIALS AND METHODS: 100 male wistar rats were divided into a blank group (nâ¯=â¯20) and a nephropathy group (nâ¯=â¯80) using random number table after 1 week adaptive feeded. Rats were injected with adriamycin (6.5â¯mg/kg) via the tail vein to induce nephropathy except for blank group. Every rat's urine protein was checked with urine protein dipstick test after three days that showed all rats in nephropathy group were successful modelled. Nephropathy group was divided into model group, benazepril group, ShenYanXiaoBai low dose group, ShenYanXiaoBai high dose group equally. Blank and model group were given distilled water 2â¯ml as control, then benazepril group received benazepril 0.90â¯mg/kg, ShenYanXiaoBai low dose group received ShenYanXiaoBai granules 1.80â¯g/kg as high dose group was given 3.60â¯g/kg, gavage for 6 days a week last for seven weeks. Urinary albumin/urinary creatinine were measured in seventh day every week. Three rats were randomly selected from each group to be executed in 3th and 5th weekend to detect the mRNA and protein expression level in kidney. The rest rats were as well. CONCLUSIONS: The therapeutic effect of ShenYanXiaoBai high dose group was better than the two other treated groups from the 5th week to the 7th week, the comparison had a significant difference. The therapeutic effect of benazepril group was better than the ShenYanXiaoBai low dose group in the 7 weeks and the comparison had a significant difference.
Assuntos
Nefropatias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Proteinúria/tratamento farmacológico , Animais , Creatinina/urina , Doxorrubicina , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Testes de Função Renal , Masculino , Medicina Tradicional Chinesa , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Substâncias Protetoras/farmacologia , Proteinúria/induzido quimicamente , Proteinúria/metabolismo , Proteinúria/patologia , Distribuição Aleatória , Ratos WistarRESUMO
BACKGROUND: Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that renal proximal tubular epithelial cells participate in uric acid excretion in chickens, the roles of BCRP and MRP4 therein remain unclear. This study evaluated the relationship between BCRP and MRP4 expression and renal function in chickens. RESULTS: Sixty laying hens were randomly divided into four treatment groups: a control group (NC) fed a basal diet; a sulfonamide-treated group (SD) fed the basal diet and supplemented with sulfamonomethoxine sodium via drinking water (8 mg/L); a fish meal group (FM) fed the basal diet supplemented with 16% fishmeal; and a uric acid injection group (IU) fed the basal diet and intraperitoneally injected with uric acid (250 mg/kg body weight). The results showed that serum uric acid, creatinine, and blood urea nitrogen levels were significantly higher in the SD and IU, but not FM, than in the NC groups. Renal tubular epithelial cells in the SD and IU groups were damaged. Liver BCRP and MRP4 mRNA and protein levels were significantly decreased in the SD and IU groups, but slightly increased in the FM group. In the SD group, BCRP and MRP4 were significantly increased in the ileum and slightly increased in the kidney. In the FM group, BCRP and MRP4 were significantly increased in the kidney and slightly increased in the ileum. In the IU group, BCRP and MRP4 were significantly increased in the kidney and ileum. BCRP and MRP4 expression in the jejunum was not affected by the treatments. CONCLUSION: Together, these results demonstrate that BCRP and MRP4 are involved in renal and intestinal uric acid excretion in chickens and that BCRP is positively related to MRP4 expression. Further, impairment of renal function results in an increase in serum uric acid as well as a compensatory increase in BCRP and MRP4 in the ileum; however, under normal renal function, renal BCRP and MRP4 are the main regulators of uric acid excretion.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Galinhas/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Ácido Úrico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Nitrogênio da Ureia Sanguínea , Galinhas/sangue , Células Epiteliais/ultraestrutura , Feminino , Mucosa Intestinal/metabolismo , Rim/metabolismo , Rim/ultraestrutura , Túbulos Renais/ultraestrutura , Fígado/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , RNA Mensageiro/metabolismo , Ácido Úrico/sangueRESUMO
Glomerulonephritis is the major cause of chronic kidney disease characterized by mesangial cell proliferation and extracellular matrix deposition. The aim of this study was to investigate the effects of Lycium barbarum polysaccharides (LBPs) on anti-Thy 1 nephritis rats and explore the protective mechanism of LBPs. After the model of glomerulonephritis created by injecting anti-thymocyte serum (ATS), rats were treated with enalapril or LBPs for 8 weeks. The therapeutic effect was evaluated by detection of renal-related biochemical parameters, histological observation and markers of renal fibrosis. Moreover, RNA-seq analysis and experiments in vitro were employed to explore the signaling pathway involved in LBPs treatment. The results found that LBPs treatment significantly suppressed ATS-caused increment at levels of blood urea nitrogen, creatinine, proteinuria, PAI-1 protein expression, glomerular mesangial cell proliferation and extracellular matrix hyperplasia, along with reduction of creatinine clearance. RNA sequencing showed pyruvate metabolism acting as a potential signaling pathway, which was evidenced by the inhibitory effect on up-regulation of pyruvate dehydrogenase and PAI-1 levels via treatment with LBPs in vitro. LBPs are the promising agents for the management of glomerulonephritis through pyruvate metabolism signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/enzimologia , Isoanticorpos/imunologia , Complexo Piruvato Desidrogenase/metabolismo , Animais , Medicamentos de Ervas Chinesas/farmacologia , Fibrose , Glomerulonefrite/genética , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Rim/ultraestrutura , Testes de Função Renal , Masculino , Camundongos , Piruvatos/metabolismo , Ratos Sprague-Dawley , Coloração e RotulagemRESUMO
Membranous nephropathy (MN) is one of the leading causes of nephrotic syndrome in adults. However, the current treatment of MN has been a matter of fierce debate for decades, and the needs for more advanced pharmaceuticals are critical for improving the treatment strategies. Sanqi oral solution (SQ), mainly consisting of Radix Astragali and Radix Notoginseng, is a formulated product to treat chronic kidney disease for over 20 years with good efficiency in clinic, while the role of SQ on MN remains unclear. In this study, by establishing an experimental rat model of membranous nephropathy induced by cationic Bovine Serum Albumin (C-BSA), we tried to investigate the effects of SQ. We found that administration of SQ ameliorated MN by reducing proteinuria, elevating serum albumin, and ameliorating pathological renal damages. SQ also significantly reduced the C3 and IgG depositions, and restored podocin and synaptopodin expressions. Furthermore, SQ inhibited the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Our results provide evidence that SQ exerts a novel therapeutic effect on MN via reducing proteinuria, ameliorating renal damage and restoring podocyte injuries, which are associated with the suppression of NFκB.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Rim/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Podócitos/efeitos dos fármacos , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/urina , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/patologia , Rim/imunologia , Rim/ultraestrutura , Masculino , Podócitos/imunologia , Podócitos/ultraestrutura , Ratos Sprague-Dawley , SoluçõesRESUMO
Diabetic nephropathy (DN) is one of the leading causes of death in diabetes mellitus (DM). Early warning and therapy has significant clinical value for DN. This research sought to find biomarkers to predict the occurrence and development of DN and the intervention of Ginkgo biloba leaves extract (GBE) by quantifying fatty acids, amino acids, and nucleosides and nucleobases in rat plasma. Samples were respectively collected at the weekend of 5-10 weeks after diabetic rats induced by streptozotocin were defined. Plasma fasting blood-glucose, kidney index, blood urea nitrogen, creatinine, urine albumin excretion and ultrastructural morphology of kidney were measured or observed. Fatty acids, amino acids and nucleosides and nucleobases in rat plasma were analyzed by gas chromatography or liquid phase chromatography and mass spectrometry, respectively. From the biochemical index and morphological change of kidney, the rats from the 5th to 7th week were in the stage of DM while from the begin of 8th week the rats were suggested in the early stage of DN. The results of quantitative metabolomics showed that 16 differential metabolites were related to the progression of DN, and oleic acid, glutamate and guanosine might be the potential biomarkers of kidney injury. 14 differential metabolites were related to GBE against the progression of DN, while oleic acid and glutamate might be the potential biomarkers of GBE against kidney injury. Those findings potentially promote the understanding of the pathogenic progression of DN and reveal the therapeutic mechanism of GBE against DN.
Assuntos
Aminoácidos/sangue , Nefropatias Diabéticas/sangue , Ácidos Graxos/sangue , Metabolômica , Nucleosídeos/sangue , Extratos Vegetais/uso terapêutico , Albuminúria , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Ginkgo biloba , Rim/patologia , Rim/ultraestrutura , Masculino , RatosRESUMO
In the present study, we have evaluated the nephroprotective effect of hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity model. Standardised extract was orally administered to Wistar rats for 10 days at different doses. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. T. chebula, in a dose-dependent manner significantly inhibited the elevation of serum creatinine, blood urea nitrogen and oxidant stress markers. The immunohistochemical analysis revealed the increased levels of apoptotic markers and cytokines in cisplatin group were significantly lowered by T. chebula extract. The cisplatin-treated rats kidney showed diffused tubular necrosis and infilteration of inflammatory cells which was reversed in the treatment group. Chemical characterisation of extract by HPLC revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and ellagic acid. The findings of this study discovered that T. chebula ameliorated oxidative and histological damage caused by cisplatin.
Assuntos
Cisplatino/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Extratos Vegetais/farmacologia , Terminalia/química , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Rim/patologia , Rim/ultraestrutura , Nefropatias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/análise , Ratos WistarRESUMO
BACKGROUND: COQ2 mutations cause a rare infantile multisystemic disease with heterogeneous clinical features. Promising results have been reported in response to Coenzyme Q10 treatment, especially for kidney involvement, but little is known about the long-term outcomes. METHODS: We report four new patients from two families with the c.437GâA (p.Ser146Asn) mutation in COQ2 and the outcomes of two patients after long-term coenzyme Q10 treatment. RESULTS: Index cases from two families presented with vomiting, nephrotic range proteinuria, and diabetes in early infancy. These patients were diagnosed with coenzyme Q10 deficiency and died shortly after diagnosis. Siblings of the index cases later presented with neonatal diabetes and proteinuria and were diagnosed at the first day of life. Coenzyme Q10 treatment was started immediately. The siblings responded dramatically to coenzyme Q10 treatment with normalized glucose and proteinuria levels, but they developed refractory focal clonic seizures beginning at three months of life that progressed to encephalopathy. CONCLUSIONS: In our cohort with CoQ10 deficiency, neurological involvement did not improve with oral coenzyme Q10 treatment despite the initial recovery from the diabetes and nephrotic syndrome.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Ataxia/dietoterapia , Ataxia/genética , Doenças Mitocondriais/dietoterapia , Doenças Mitocondriais/genética , Debilidade Muscular/dietoterapia , Debilidade Muscular/genética , Ubiquinona/análogos & derivados , Ubiquinona/deficiência , Ataxia/complicações , Ataxia/diagnóstico por imagem , Estudos de Coortes , Diabetes Mellitus/etiologia , Saúde da Família , Feminino , Humanos , Lactente , Rim/patologia , Rim/ultraestrutura , Imageamento por Ressonância Magnética , Masculino , Doenças Mitocondriais/complicações , Doenças Mitocondriais/diagnóstico por imagem , Debilidade Muscular/complicações , Debilidade Muscular/diagnóstico por imagem , Mutação/genética , Proteinúria/etiologia , Ubiquinona/genética , Ubiquinona/uso terapêuticoRESUMO
Combination antiretroviral therapy (cART) has shown to cause inflammation, cellular injury and oxidative stress, whereas melatonin has been successful in reducing these effects. The aim of the study was to determine potential morphometric changes caused by cART in combination with melatonin supplementation in human immunodeficiency virus (HIV)-free rats. Tissue samples (Nâ¯=â¯40) of the pancreas, liver and kidney from a control (C/ART-/M-), cART group (C/ARTâ¯+â¯), melatonin (C/Mâ¯+â¯) and experimental group (ART+/Mâ¯+â¯) were collected and stained with haematoxylin and eosin (H&E) and evaluated for histopathology. The pancreata were labelled with anti-insulin and anti-glucagon to determine α- and ß-cell regions. Kidneys were stained with periodic acid Schiff (PAS) to measure the area, perimeter, diameter and radius of renal corpuscles, glomeruli and proximal convoluted tubules (PCTs). Blood tests were conducted to determine hepatotoxicity. No significant changes in histopathology were seen. Melatonin stimulated pancreatic islet abundance, as the number of islets per mm2 was significantly higher in the C/M+ than in the C/ART-/M- and ART+/M+. Parameters of the renal corpuscle, glomeruli, renal space and PCTs were significantly lower in the C/ART+ compared to the other groups, thus cART may have caused tubular dysfunction or cellular damage. A significant increase in serum haemoglobin was observed in the C/ART+ compared to the C/ART-, which showed cART increases serum haemoglobin in the absence of immune deficiency. Serum lipids were significantly decreased in the C/M+ compared to the C/ART-, possibly due to the effect of melatonin on the decrease of lipolysis, decreasing effect on cholesterol absorption and stimulation of lipoprotein lipase (LPL) activity. In conclusion, we have demonstrated that melatonin stimulated α-cell production, increased the number of pancreatic islets and caused a decrease in total lipids, whereas cART increased serum haemoglobin and decreased various parameters of the nephron in an HIV-free rat model, suggestive of tubular dysfunction.
Assuntos
Antirretrovirais/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Melatonina/farmacologia , Pâncreas/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , HIV , Imuno-Histoquímica , Inflamação , Ilhotas Pancreáticas/ultraestrutura , Rim/ultraestrutura , Fígado/ultraestrutura , Testes de Função Hepática , Masculino , Pâncreas/ultraestrutura , Ratos , Padrões de ReferênciaRESUMO
OBJECTIVES: Acquired aplastic anemia (AA) is a hematopoietic stem cell disease that leads to hematopoietic disorder and peripheral blood pancytopenia. We investigated whether nutritional support is helpful to AA recovery. METHODS: We established a rat model with AA. A nutrient mixture was administered to rats with AA through different dose gavage once per day for 55 d. Animals in this study were assigned to one of five groups: normal control (NC; group includes normal rats); AA (rats with AA); high dose (AA + nutritional mixture, 2266.95 mg/kg/d); medium dose (1511.3 mg/kg/d); and low dose (1057.91 mg/kg/d). The effects of nutrition administration on general status and mitochondrial function of rats with AA were evaluated. RESULTS: The nutrient mixture with which the rats were supplemented significantly improved weight, peripheral blood parameters, and histologic parameters of rats with AA in a dose-dependent manner. Furthermore, we observed that the number of mitochondria in the liver, spleen, kidney, and brain was increased after supplementation by transmission electron microscopy analysis. Nutrient administration also improved mitochondrial DNA content, adenosine triphosphate content, and membrane potential but inhibited oxidative stress, thus, repairing the mitochondrial dysfunction of the rats with AA. CONCLUSIONS: Taken together, nutrition supplements may contribute to the improvement of mitochondrial function and play an important role in the recuperation of rats with AA.
Assuntos
Anemia Aplástica/fisiopatologia , Anemia Aplástica/terapia , Mitocôndrias/fisiologia , Apoio Nutricional/métodos , Trifosfato de Adenosina/análise , Anemia Aplástica/patologia , Animais , Encéfalo/ultraestrutura , DNA/análise , Modelos Animais de Doenças , Rim/ultraestrutura , Potencial da Membrana Mitocondrial/fisiologia , Microscopia Eletrônica de Transmissão , Mitocôndrias/química , Mitocôndrias/patologia , Mitocôndrias Hepáticas/patologia , Mitocôndrias Hepáticas/fisiologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Baço/ultraestruturaRESUMO
The antioxidant effects of water-ethanol extract (WEE) from Turnera diffusa (damiana) in kidney mitochondria from experimental streptozotocin-induced diabetes mellitus (STZ-DM) rats was evaluated. STZ-DM rats were orally treated during three and five weeks. After experimental periods, kidney mitochondria were isolated and malondialdehyde (MDA), nitric oxide (NOâ¢) and protein nitrosylation levels were measured. Also, blood glucose (BG) and body weight (BW) were recorded. Damiana significantly reduced the MDA and NO⢠levels in kidney mitochondria, although no changes in protein nitrosylation were observed and it did not have the potential to reverse the hyperglycaemia. In conclusion, WEE of T. diffusa have antioxidant properties that may prevent damage induced by mitochondrial oxidative stress in kidneys of STZ-DM rats.
Assuntos
Antioxidantes/farmacologia , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Turnera/química , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Rim/metabolismo , Rim/ultraestrutura , Masculino , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Estreptozocina/farmacologiaRESUMO
Gentamicin is a potent aminoglycoside antibiotic, but the risk of nephrotoxicity limits its prolonged use. The toxicity of gentamicin is believed to result from oxidative stress, a condition that could be counteracted by dietary antioxidants. This study determines the possible renoprotective effects of kiwifruit against the pathophysiological and ultrastructural alterations induced by gentamicin. Mice were intraperitoneally injected with gentamicin (100mg/kg body weight) for eight consecutive days, and kiwi juice was administered for 8days, either concomitant to or after gentamicin injection. Gentamicin caused nephrotoxicity evidenced by the significant elevation of serum creatinine and blood urea nitrogen levels, along with significant reduction of serum sodium and potassium ions, compared to normal controls. This was associated with proximal tubular necrosis, lysosomal accumulation and mitochondrial alterations, together with glomerular atrophy, mesangial hypercellularity, and inflammatory cell infiltration. Moreover, immunohistochemical results pointed to the relevant role of Nrf2 and NF-κB in gentamicin-induced nephrotoxicity. Kiwi administration, especially when given after gentamicin injection, significantly ameliorated gentamicin-induced pathophysiological alterations, increased the nuclear immunoreactivity of Nrf2 and decreased that of NF-κB. In short, kiwi fruit shows a promising role as a nephroprotective agent against gentamicin-induced nephrotoxicity via attenuating oxidative stress, inflammation and cell death.
Assuntos
Actinidia/química , Antibacterianos/toxicidade , Gentamicinas/toxicidade , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Preparações de Plantas/uso terapêutico , Animais , Sucos de Frutas e Vegetais , Rim/metabolismo , Rim/ultraestrutura , Nefropatias/induzido quimicamente , Testes de Função Renal , Masculino , Camundongos , Preparações de Plantas/administração & dosagemRESUMO
Molybdenum (Mo) is an essential element for human beings and animals; however, high dietary intake of Mo can lead to adverse reactions. Cadmium (Cd) is one of the major transitional metals which has toxic effects in animals. To investigate the co-induced toxic effects of Mo and Cd on oxidative damage and kidney apoptosis in duck, 120 ducks were randomly divided into control group and 5 treatment groups which were treated with a commercial diet containing different dosages of Mo and Cd. Kidney samples were collected on the 60th and 120th days to determine the mRNA expression levels of ceruloplasmin (CP), metallothionein (MT), Bak-1, and Caspase-3 by quantitative RT-PCR. Additionally, we also determined the antioxidant activity indexes and contents of Mo, Cd, copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) in serum. Meanwhile, ultrastructural changes of the kidney were observed. The results showed that glutathione reductase (GR) activity and CP level in serum were decreased in combination groups. In addition, the antioxidant indexes were decreased in co-treated groups compared with single treated groups. The mRNA expression levels of Bak-1 and Caspase-3 increased in co-treated groups. The mRNA expression level of CP in high-dose combination group was downregulated, while the mRNA expression of MT was upregulated except for low-dose Mo group. Additionally, in the later period the content of Cu in serum decreased in joint groups while the contents of Mo and Cd increased. In addition, ultrastructural changes showed mitochondrial crest fracture, swelling, deformed nuclei, and karyopyknosis in co-treated groups. Taken together, it was suggested that dietary Mo and Cd might lead to oxidative stress, kidney apoptosis and disturb homeostasis of trace elements in duck, and it showed a possible synergistic relationship between the two elements.
Assuntos
Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Patos/metabolismo , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Molibdênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Rim/metabolismo , Rim/ultraestrutura , Oligoelementos/toxicidadeRESUMO
Diabetes mellitus is a chronic multi-factorial metabolic disorder resulting from impaired glucose homeostasis. Zinc is a key co-factor for the correct functioning of anti-oxidant enzymes. Zinc deficiency therefore, impairs their synthesis, leading to increased oxidative stress within cells. Zinc deficiency occurs commonly in diabetic patients. The aim of this study is to investigate the effects of varying concentrations of zinc on diabetic nephropathy (DN) and the underlying mechanisms involved. FVB male mice aged 8 weeks were injected intraperitoneally with multiple low-dose streptozotocin at a concentration of 50mg/kg body weight daily for 5 days. Diabetic and age-matched control mice were treated with special diets supplemented with zinc at varying concentrations (0.85mg/kg, 30mg/kg, 150mg/kg) for 3 months. The mice were fed with zinc diets to mimic the process of oral administration of zinc in human. Zinc deficiency to some extent aggravated the damage of diabetic kidney. Feeding with normal (30mg/kg zinc/kg diet) and especially high (150mg/kg zinc/kg diet) concentration zinc could protect the kidney against diabetes-induced damage. The beneficial effects of zinc on DN are achieved most likely due to the upregulation of Nrf2 and its downstream factors NQO1, SOD1, SOD2. Zinc upregulated the expression of Akt phosphorylation and GSK-3ß phosphorylation, resulting in a reduction in Fyn nuclear translocation and export of Nrf2 to the cytosol. Thus, regular monitoring and maintaining of adequate levels of zinc are recommended in diabetic individuals in order to delay the development of DN.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Zinco/uso terapêutico , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Glicogênio Sintase Quinase 3 beta/metabolismo , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Rim/ultraestrutura , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina/administração & dosagem , Zinco/farmacologiaRESUMO
Subcutaneous daily injection (with neglect of aseptics) of 0.5 ml solution of soybean cream substitute (10% volume in distilled water) during 30 days caused systemic amyloidosis in 30-day-old mice. All the known methods for induction of systemic amyloidosis are based on the use of old animals, as senile tissue bradytrophy allows effective simulation of amyloidosis.
Assuntos
Amiloide/ultraestrutura , Amiloidose/patologia , Modelos Animais de Doenças , Nanopartículas/toxicidade , Creme para a Pele/toxicidade , Idade de Início , Amiloidose/induzido quimicamente , Amiloidose/metabolismo , Animais , Carotenoides/química , Emulsificantes/química , Xarope de Milho Rico em Frutose/química , Injeções Subcutâneas , Rim/metabolismo , Rim/patologia , Rim/ultraestrutura , Fígado/metabolismo , Fígado/patologia , Fígado/ultraestrutura , Masculino , Camundongos , Nanopartículas/administração & dosagem , Dióxido de Silício/química , Creme para a Pele/administração & dosagem , Óleo de Soja/química , Baço/metabolismo , Baço/patologia , Baço/ultraestruturaRESUMO
Hyperglycemia and mitochondrial ROS overproduction have been identified as key factors involved in the development of diabetic nephropathy. This has encouraged the search for strategies decreasing glucose levels and long-term improvement of redox status of glutathione, the main antioxidant counteracting mitochondrial damage. Previously, we have shown that avocado oil improves redox status of glutathione in liver and brain mitochondria from streptozotocin-induced diabetic rats; however, the long-term effects of avocado oil and its hypoglycemic effect cannot be evaluated because this model displays low survival and insulin depletion. Therefore, we tested during 1 year the effects of avocado oil on glycemia, ROS levels, lipid peroxidation and glutathione status in kidney mitochondria from type 2 diabetic Goto-Kakizaki rats. Diabetic rats exhibited glycemia of 120-186 mg/dL the first 9 months with a further increase to 250-300 mg/dL. Avocado oil decreased hyperglycemia at intermediate levels between diabetic and control rats. Diabetic rats displayed augmented lipid peroxidation and depletion of reduced glutathione throughout the study, while increased ROS generation was observed at the 3rd and 12th months along with diminished content of total glutathione at the 6th and 12th months. Avocado oil ameliorated all these defects and augmented the mitochondrial content of oleic acid. The beneficial effects of avocado oil are discussed in terms of the hypoglycemic effect of oleic acid and the probable dependence of glutathione transport on lipid peroxidation and thiol oxidation of mitochondrial carriers.