RESUMEN
Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.
Asunto(s)
Antioxidantes/uso terapéutico , Dioxoles/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Lignanos/uso terapéutico , Fitoterapia , Sesamum , Animales , Antineoplásicos/efectos adversos , Antioxidantes/farmacología , Cisplatino/efectos adversos , Dioxoles/farmacología , Evaluación Preclínica de Medicamentos , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Lignanos/farmacología , Masculino , Extractos Vegetales/uso terapéutico , Ratas WistarRESUMEN
The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.
Asunto(s)
Amidas/administración & dosificación , Fumaratos/administración & dosificación , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Sistema Renina-Angiotensina/efectos de los fármacos , Daño por Reperfusión/prevención & control , Daño por Reperfusión/fisiopatología , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Fármacos Renales/administración & dosificación , Circulación Renal/efectos de los fármacos , Renina/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
BACKGROUND: The anticancerdrug cisplatin (CP) causes nephrotoxicity through different mechanisms, including generation of free radicals. Ellagic acid (EA) is a polyphenolic antioxidant found in fruits and nuts. AIM: This study aimed to investigate the ability of different doses of EA to ameliorate CP nephrotoxicity in rats. MATERIALS AND METHODS: Animals were randomly divided into six groups and treated with saline; CP alone (6 mg/kg); two doses of EA, both alone (10 and 30 mg/kg) or with CP. RESULTS: Treatment with CP alone reduced body weight, water intake, urine output, and renal total antioxidant and reduced glutathione (GSH) concentrations (p < 0.01). In addition, it increased relative kidney weight, plasma creatinine, and blood urea nitrogen (BUN) concentrations (p < 0.01). However, a dose of 30 mg/kg EA mitigated most of the CP-induced actions, but no effect was seen for the 10 mg/kg dose. Histopathologically, rats given CP+EA30 showed < 25% necrotic lesions in the renal cortical area compared with > 60% in rats treated with CP alone. Molecular analysis showed that clusterin (Clu) mRNA and protein were expressed in all treated groups, meanwhile kidney injury molecule-1 (Kim-1) mRNA and protein were only expressed in the CP and CP+EA treated rats. CONCLUSIONS: EA (30 mg/kg) ameliorated most of the physiological, histological, and biochemical markers of CP nephrotoxicity. The molecular findings in this work did not completely tally with the conventional method used. The overexpression of the molecular markers may be related to the EA induced repair mechanism.
Asunto(s)
Antioxidantes/farmacología , Cisplatino/toxicidad , Ácido Elágico/farmacología , Enfermedades Renales/prevención & control , Animales , Antineoplásicos/toxicidad , Antioxidantes/administración & dosificación , Moléculas de Adhesión Celular/genética , Clusterina/genética , Relación Dosis-Respuesta a Droga , Ácido Elágico/administración & dosificación , Femenino , Enfermedades Renales/inducido químicamente , Enfermedades Renales/fisiopatología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-alpha was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-alpha in all groups. Curcumin significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI.
Asunto(s)
Lesión Renal Aguda/prevención & control , Lesión Renal Aguda/fisiopatología , Curcumina/uso terapéutico , Circulación Renal/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , Lesión Renal Aguda/etiología , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/complicaciones , Resultado del TratamientoRESUMEN
AIM: To evaluate peritoneal resorption capacity for lipopolysaccharide (LPS) and interleukin-6 (IL-6) in a model of chemical peritonitis. METHODS: Zymosan peritonitis was induced in anesthetized rats. LPS was injected intraperitoneally to different groups at 4 h (n = 10), 8 h (n = 9), 12 h (n = 9), and 24 h (n = 9) after peritonitis and to a control group (n = 8). Similarly, IL-6 was injected intraperitoneally to different groups at 4 h (n = 9), 8 h (n = 10), 12 h (n = 10), and 24 h (n = 10) after peritonitis, and to a control group (n = 10). Plasma levels of LPS or IL-6 were measured immediately after intraperitoneal injections of LPS or IL-6, respectively, and at 5, 15, 30, 45, and 60 min later. RESULTS: There was no change over time in plasma LPS levels in the groups receiving LPS intraperitoneally (p = 0.4). There was highly significant change over time in the IL-6 level in the studied time periods in the groups receiving IL-6 intraperitoneally (p < 0.0001). There was an increase in the plasma IL-6 level when sampled at 4 h after peritonitis. CONCLUSION: There was a reduction of resorption capacity of inflamed peritoneum for inflammatory mediators in acute chemical peritonitis.
Asunto(s)
Interleucina-6/farmacocinética , Lipopolisacáridos/farmacocinética , Peritonitis/inducido químicamente , Peritonitis/fisiopatología , Animales , Mediadores de Inflamación/administración & dosificación , Mediadores de Inflamación/sangre , Mediadores de Inflamación/farmacocinética , Interleucina-6/administración & dosificación , Interleucina-6/sangre , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/sangre , Masculino , Peritoneo/patología , Peritoneo/fisiopatología , Peritonitis/patología , Ratas , Ratas Wistar , Zimosan/toxicidadAsunto(s)
Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Neoplasias de la Glándula Submandibular/patología , Biopsia con Aguja Fina , Niño , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Neoplasias de la Glándula Submandibular/cirugía , Resultado del TratamientoRESUMEN
We describe a lupus flare in a 59-year-old woman who presented with pancytopenia, nephritis, severe renal dysfunction and marked hyperferritinemia. The course of the disease was further complicated by an iron-laden, intraspinal ancient schwannoma that compressed the cervical cord mimicking a lupus-related myelopathy and was removed surgically. Treatment with mycophenolate mofetil (MMF) and prednisone induced a gradual decline in levels of serum ferritin with a concomitant improvement in renal function and reduction of proteinuria. Serum ferritin may be a useful marker of the response to treatment with MMF in renal lupus.
Asunto(s)
Ferritinas/sangre , Nefritis Lúpica/complicaciones , Neurilemoma/complicaciones , Neurilemoma/patología , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/patología , Antirreumáticos/uso terapéutico , Vértebras Cervicales , Femenino , Humanos , Nefritis Lúpica/sangre , Nefritis Lúpica/tratamiento farmacológico , Persona de Mediana Edad , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Prednisona/uso terapéuticoRESUMEN
Gentamicin (GM) is used against serious and life-threatening infections, but its use is limited by the occurrence of nephrotoxicity, which involves the generation of free radicals. In this work we tested the effect of a compound with antioxidant properties, tertamethylpyrazine (TMP), a major constituent of the Chinese medicinal plant Lingusticum wallichi, on GM-induced nephrotoxicity, and compared it with an established anti-oxidant compound N-acetyl cysteine (NAC). Six groups of rats were studied: (1) control, treated orally (p.o.) and intraperitoneally (i.p.) with saline; (2) treated i.p. with GM (80 mg kg(-1) per day for 6 days); (3) TMP, given p.o. (100 mg kg(-1) per day for 10 days) + GM (same dose as above during the last 6 days); (4) NAC, given i.p. (500 mg kg(-1) per day for 10 days) + GM as above; (5) TMP (100 mg kg(-1) per day for 10 days) + saline; (6) NAC (500 mg kg(-1) per day for 10 days) + saline. GM nephrotoxicity was characterized by reduced creatinine clearance, increased creatinine and urea concentrations in plasma, increased urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG) and total protein. These functional and structural alterations were prevented or ameliorated by NAC treatment, while TMP had only a slight mitigating effect that was less marked than that produced by NAC. The concentration of GM in the renal cortex of the rats given GM + NAC (but not TMP) was lower than that found in rats treated with GM alone by about 25%. The mechanism by which NAC and, to a lesser extent TMP, protected against GM-induced nephrotoxicity may be related, at least in part, to the decrease in oxidative stress in renal cortex.