ABSTRACT
Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.
Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.
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Cisplatin is an effective antineoplastic agent, but its use is limited by its nephrotoxicity caused by the oxidative stress in tubular epithelium of nephrons. On the other hand, regular exercise provides beneficial adaptations in different tissues and organs. As with many drugs, dosing is extremely important to get the beneficial effects of exercise. Thus, we aimed to investigate the influence of exercise intensity and frequency on cisplatin-induced (20 mg/kg) renal damage in mice. Forty male Swiss mice were divided into five experimental groups (n=8 per group): 1) sedentary; 2) low-intensity forced swimming, three times per week; 3) high-intensity forced swimming, three times per week; 4) low-intensity forced swimming, five times per week; and 5) high-intensity forced swimming, five times per week. Body composition, renal structure, functional indicators (plasma urea), lipid peroxidation, antioxidant enzyme activity, expression of genes related to antioxidant defense, and inflammatory and apoptotic pathways were evaluated. Comparisons considered exercise intensity and frequency. High lipid peroxidation was observed in the sedentary group compared with trained mice, regardless of exercise intensity and frequency. Groups that trained three times per week showed more benefits, as reduced tubular necrosis, plasma urea, expression of CASP3 and Rela (NFkB subunit-p65) genes, and increased total glutathione peroxidase activity. No significant difference in Nfe2l2 (Nrf2) gene expression was observed between groups. Eight weeks of regular exercise training promoted nephroprotection against cisplatin-mediated oxidative injury. Exercise frequency was critical for nephroprotection.
ABSTRACT
Contrast-induced nephropathy (NIC) is directly related to increased morbidity and mortality, and its treatment and prevention might be achieved by the administration of antioxidant products. The juçara palmetto (Euterpe edulis Martius) has fruits rich in phenolic compounds, which are known for their antioxidant activity. This work aimed to evaluate the nephroprotective activity of E. edulis pulp in the NIC animal model. The collected fruits were pulped, their contents of polyphenols and anthocyanins were quantified, and their antioxidant activity were evaluated. The nephroprotective effects were determined based on iodine contrast induction and evaluated by biochemical and histological analyses. The results showed that E. edulis pulp was rich in polyphenols (811 ± 16.7 mg EAG/g) and anthocyanins (181.25 mg/100 g) and had very strong antioxidant activity, as demonstrated by the DPPH (2,2-diphenyl-1-picryl-hydrazyl) method, which revealed an antioxidant activity index (AAI) of 3.4, and the 2,29-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) method, which revealed an IC50 of 0.59 ± 0.03 mg/mL. In the in vivo experiments, E. edulis pulp tended to provide renal protection and reduce renal dysfunction and tubular morphological lesions in mice after the induction of NIC, and these effects were obtained through the antioxidant activities of the polyphenols in the pulp.
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Background: Drug induced nephrotoxicity, one of the most common renal problem, is a challenge to deal with especially in patients with renal dysfunction. It is responsible for 20% cases of acute renal failure in the community. Modern medicines are costly and have minimal nephroprotection. Solanum nigrum fruit extract, a cheaper drug, have antioxidant property and may help in nephroprotection.Methods: Total 54 rats were randomised in 3 groups named G10, G20 and G30 according to 10, 20 and 30 days of treatment. In each groups, rats were randomly assigned to any of the three subgroups i.e., control C group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration], gentamicin treated (GT) group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days] and S. nigrum treated (SNT) group [received S. nigrum orally (200 mg/kg/day) for the test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days]. Rats were sacrificed 24 hours after the last dose of gentamicin injection (on 11th, 21st and 31st day). Excised kidneys were weighted and prepared for histological examination.Results: The mean weight of kidneys in GT group was significantly higher than the SNT group in all test durations suggestive of decrease in inflammation in SNT group. This was also reflected histologically as SNT group kidney showed less amount of tubular destruction as compared to GT group.Conclusions: S. nigrum extract provide nephroprotection against gentamicin induced nephrotoxicity.
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Background: Gentamicin, an aminoglycoside group of drug, used against aerobic gram negative bacteria, is known for nephrotoxicity. Herbal products have a special place in the world of pharmaceuticals with their safety, efficacy and cost effectiveness. Withania somnifera (Ashwagandha) roots had known since long for its antioxidant status and free radical scavenging property. So W. somnifera can be used as nephroprotective agent because of free radical scavenging property.Methods: Total 54 rats were randomised in 3 groups named G10, G20 and G30 according to 10, 20 and 30 days of treatment. In each groups, rats were randomly assigned to any of the three subgroups i.e., control C group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration], gentamicin treated GT group [received normal saline (2 ml/100 gm/day) orally consecutively for test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days] and W. somnifera treated WST group [received W. somnifera orally (500 mg/kg/day) for the test duration and intraperitoneal gentamicin (40 mg/kg) once daily for last five days]. Rats were sacrificed 24 hours after the last dose of gentamicin injection. Excised kidneys were weighted and prepared for histological examination.Results: The mean weight of kidneys in GT group was significantly higher than the WST group in all test durations indicating the antioxidant and free radical scavenging property. This was also reflected histologically as WST group kidney showed less amount inflammation as compared to GT group.Conclusions: W. somnifera root extract provide nephroprotection against gentamicin induced nephrotoxicity.
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Technical grade dinitrotoluene (tg-DNT) [CH3C6H3 (NO2)2] nitroaromatic agents which are manufactured in theindustries and applied in both commercial and military in all over the world and Egypt. DNT causes malfunctions inkidneys, heart, liver, testes and mammary glands in animals and human beings, which may be considered as carcinogenic inexperimental animals and human. Moreover, taurine, a free β-amino acid with remarkable antioxidant activity, hasimportant beneficial effects on the human body; hepatoprotection, nephroprotection, cardiovascular protection,hypoglycemic impact and hypolipidemicaction. Currently, taurine level in the serum is used as early marker of breast,endometrial and colon cancers. The current research was aimed to explore the potential impacts of the antioxidantproperties of taurine as a protecting material on tg-DNT induced toxicity in the liver and kidney in male rats. 100apparently healthy male rats in 4 groups were included; the first is Frank control group, mouth feeding via gavage withdistilled water; the other groups were administered as following, taurine alone, tg-DNT alone (toxic group), taurine + tgDNT (protective group) in the second, third and fourth groups, respectively. In these groups, blood biochemistry and taurineconcentrations in serum were measured for all animals. Furthermore, histopathological examination studies for liver andkidney were done for all groups. The results showed that, the protective group has marked improvement in most biochemicalparameters than the toxic group. Histological studies revealed a significant marked disturbance in the histopathologicalarchitectures of the kidney and liver in all toxic rats. However, marked improvements in histological architectures wereobserved in protective group. The results support the ameliorative effect of taurine as a protective agent against tg-DNTtoxicity in experimental rats.
ABSTRACT
Background: Diabetic nephropathy is a leading cause of end-stage renal failure worldwide. Purpose: The methanol leaf extract of Vernonia amygdalina (MLVA) was thus investigated for its nephroprotective effects in diabetes.Materials and Methods: Diabetes was induced in male Wistar rats by a single intraperitoneal (I.P) injection of a freshly prepared solution of Alloxan monohydrate (100 mg/kg). Forty-eight hours after alloxan administration, rats with fasting blood glucose levels of 200 mg/dl and above were used for the study. Animals were grouped into five (A-E) of nine animals each. Group A was non-diabetic non treated control; Group B animals were the diabetic untreated control rats while groups C, D and E animals were diabetic and treated with glibenclamide, MLVA 200 mg/kg and MVLA 400 mg/kg respectively. Biochemical changes were evaluated by measuring the serum markers of kidney damage (creatinine and blood urea nitrogen). Markers of oxidative stress and antioxidant activities were measured in renal tissues. Histopathological and immunohistochemical changes were also evaluated.Results: Four-week administration of MLVA produced significant (p<0.05) decrease in serum creatinine, urea, and oxidative markers but it caused a significant increase in enzymic and nonenzymic antioxidant as well as downregulation of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-?B) and upregulation of B-cell lymphoma 2 (Bcl-2).Conclusion: MLVA ameliorates diabetic nephropathy through its antioxidant, anti-inflammatory and antiapoptotic effects
ABSTRACT
Resumen: La diabetes mellitus 2 es una epidemia mundial, aunado a esto, la nefropatía diabética se ha convertido en la principal causa de insuficiencia renal en etapa terminal. En los pacientes con diabetes mellitus 2 existe sobreexpresión de los cotransportadores de glucosa ligados a la vía del sodio tipo 2 (SGLT2) que contribuyen al mantenimiento de la hiperglucemia. Por tanto, los inhibidores de este transportador representan un tratamiento innovador independiente de la acción de la insulina o la función de las células beta pancreáticas. En estudios recientes se ha demostrado que los iSGLT2 tienen efectos benéficos en la microvasculatura, en especial en la progresión de la nefropatía diabética. Este efecto no sólo se debe a la mejora del control glucémico, sino también a efectos directos en el riñón. Los iSGLT2, al inducir la glucosuria, revierten la glucotoxicidad renal. En estudios experimentales se ha observado que, además, se reduce la hiperfiltración, así como los marcadores inflamatorios y fibróticos. También se ha visto reducción del volumen circulante efectivo y aumento en la actividad de bloqueadores del sistema renina-angiotensina-aldosterona (bloqueadores RAA) circulantes, creando así un efecto nefroprotector.
Abstract: Type 2 diabetes mellitus 2 (DM2) is already a worldwide epidemic, in addition, diabetic nephropathy has become the leading cause of end-stage renal failure. In patients with DM2 there is an increased expression of the sodium-glucose cotransporters 2 (SGLT2) that contribute to the maintenance of hyperglycemia. Therefore, the inhibitors of this transporter represent an innovative therapy independent of the action of insulin or the function of pancreatic beta cells. Recent studies have shown that iSGLT2 have beneficial effects on microvasculature, especially in the progression of diabetic nephropathy. This effect is due not only to improved glycemic control but also to direct effects on the kidney. iSGLT2 induce glycosuria to reverse renal glucotoxicity. In experimental studies it has been observed that, in addition, hyper-filtration as well as inflammatory and fibrotic markers are reduced. There has also been a reduction in effective circulating volume and an increase in the activity of circulating renin-angiotensin-aldosterone system blockers (RAA blockers), thus creating a nephroprotective effect.
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Abstract In recent years, several new antidiabetic drugs have been developed, among which only two have demonstrated superiority in cardiovascular protection. They are liraglutide and empagliflozine, which belong, respectively, to GLP-1 RA and SGLT-2Í. These medications have also shown benefits in kidney protection. However, in a recent survey of the author among nephrologists in a large colombian city, it has been detected that most do not use these drugs. The greater resistance to the limitation in its use is due to the advanced stages of chronic kidney disease where they are contraindicated, but also to the anawareness of their potential benefits. In this regard, the nephrologists accepted they should learn more about these antidiabetic medicines, because the type of patient that is frequently attended in their consultation will undoubtly benefit, and considering they are obligated to handle the diabetic patient directly.
Resumen En los últimos años se han desarrollado nuevos fármacos antidiabéticos, entre los que sólo dos han demostrado superioridad en protección cardiovascular. Son liraglutida y empagliflozina, que pertenecen, respectivamente, a los grupos GLP-1 RA y SGLT-2Í. Estos medicamentos también han demostrado beneficios en nefroprotección. Sin embargo, en una reciente encuesta del autor entre nefrólogos, en una gran ciudad colombiana, se ha detectado que la mayoría no utilizan estos fármacos. La mayor resistencia a su uso se debe a consideraciones sobre su restricción en etapas avanzadas de la enfermedad renal crónica, pero también al desconocimiento de sus beneficios potenciales. Al respecto, los nefrólogos aceptaron que deberían aprender más acerca de estos medicamentos antidiabéticos, porque el tipo de paciente que frecuentemente asiste a su consulta sin duda se beneficiaría, y más teniendo en cuenta que por el gran número de diabéticos los nefrólogos están obligados a manejar directamente al paciente con esta patología.
Subject(s)
Humans , Cardiovascular Agents , Nephrologists , Hypoglycemic Agents , Cardiotonic Agents , Colombia , Diabetes Mellitus, Type 2 , LiraglutideABSTRACT
La insuficiencia renal es una comorbilidad frecuente en pacientes con diabetes mellitus (DM) e incrementa en ellos el riesgo cardiovascular; la hiperglucemia crónica en pacientes con DM induce una gran cantidad de alteraciones directas e indirectas en la estructura y la función renal, y constituye el principal factor para el desarrollo de la nefropatía diabética y la enfermedad renal terminal. En la presente revisión, se exponen los resultados de los estudios en los que se ha demostrado la alta tolerabilidad de empagliflozina en pacientes diabéticos con insuficiencia renal concomitante en estadios I a III. Empagliflozina, mediante la inhibición de SGLT2, ofrece una terapia novedosa con efectos benéficos no sólo sobre el control glucémico, sino también beneficios cardiovasculares y renales, los cuales han sido demostrados en el estudio EMPA-REG OUTCOME y continúan en evaluación en otros estudios
Chronic kidney disease is a frequent comorbidity in patients with diabetes mellitus (DM) and it increases their cardiovascular risk; chronic hyperglycemia in patients with DM leads to direct and indirect disorders in kidney's structure and function, and it is the principal risk factor for the development of diabetic nephropathy and end-stage renal disease. In the current review, results of studies are exposed in which high tolerability of empagliflozin is exposed in diabetic patients with kidney disease. Empagliflozin by inhibiting SGLT2 provides a novel therapy with benefic effects, not only in glycemic control, but it also has cardiovascular and renal benefits, which they have been demonstrated in the EMPA-REG OUTCOME trial, and continue in evaluation in other studies
Subject(s)
Humans , Diabetes Complications , Diabetes Complications/therapy , Diabetes Mellitus , Sodium-Glucose Transport Proteins , Glycemic Index , Diabetic NephropathiesABSTRACT
Background: Non-steroidal anti-inflammatory drugs are very commonly used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet agent. They have significant adverse effect on liver and kidney besides damaging stomach. Their effect on liver and kidney are of serious concern. Hence, we have decided to study the preventive effect of Nigella sativa against paracetamol induced hepatic and renal damages. Methods: Ethanolic and aqueous extracts of N. sativa were prepared with the help of Soxhlet’s apparatus. Totally, 36 wistar albino rats (150-200 g) of either sex were divided into six groups of six each. Group I was administered with distilled water, Group II-VI were treated with paracetamol 750 mg/kg i.p. Group III-VI were test groups also treated with N. sativa aqueous extract (200 and 400 mg/kg p.o) and ethanolic extract (200 and 400 mg/kg p.o), respectively. The treatment was given daily for 7 days and on 8th all the rats were sacrificed and the blood was analyzed for hepatic and renal function tests and tissue was preserved for histopathological examination. Results: Paracetamol administration caused a marked hepatic and renal damage, which is evidenced by the increase in liver and renal function test parameters in the negative control group. N.sativa extracts prevented this damage. The protective was seen maximum in ethanolic extract followed by the aqueous extract in dosedependent manner. Conclusion: Ethanolic extract showed significant protection against paracetamolinduced and renal damage.
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Background: Present study aimed to study effect of Salacia Chinensis, a herbal drug, on stabilization of renal functions, and markers of endothelial dysfunction in diabetic chronic kidney disease (CKD) patients. Materials and Methods: 30 stable diabetic CKD patients were randomized into 2 groups; group A and B of 15 patients each. Group A was given trial drug Salacia chinensis 1000 mg twice-daily while group B received placebo. Measures of renal function: Serum creatinine and creatinine clearance; markers of endothelial dysfunction: Interleukin-6 and serum Homocysteine, and lipid profile were measured at baseline and during follow-up period of 6 months. Results : There was stabilization of renal function as measured by serum creatinine and creatinine clearance in patients who received Salacia Chinensis compared to placebo (P value < 0.05), suggesting that Salacia chinensis may retard the progression of chronic kidney disease. Similarly, there was significant decline in both serum homocysteine and IL-6 levels. [P value < 0.05 for both]. Conclusion: This pilot study showed a promising role for Salacia chinensis as a renoprotective drug, but further prospective studies involving large number of patients are needed to confirm this and also to delineate possible mechanisms.