Capsaicin Decreases Kidney Iron Deposits and Increases Hepcidin Levels in Diabetic Rats with Iron Overload: A Preliminary Study.

Iron overload (IOL) increases the risk of diabetes mellitus (DM). Capsaicin (CAP), an agonist of transient receptor potential vanilloid-1 (TRPV1), reduces the effects of IOL. We evaluated the effects of chronic CAP administration on hepcidin expression, kidney iron deposits, and urinary biomarkers in a male Wistar rat model with IOL and DM (DM-IOL). IOL was induced with oral administration of iron for 12 weeks and DM was induced with streptozotocin. Four groups were studied: Healthy, DM, DM-IOL, and DM-IOL + CAP (1 mg·kg-1·day-1 for 12 weeks). Iron deposits were visualized with Perls tissue staining and a colorimetric assay. Serum hepcidin levels were measured with an enzyme-linked immunosorbent assay. Kidney biomarkers were assayed in 24 h urine samples. In the DM-IOL + CAP group, the total area of iron deposits and the total iron content in kidneys were smaller than those observed in both untreated DM groups. CAP administration significantly increased hepcidin levels in the DM-IOL group. Urinary levels of albumin, cystatin C, and beta-2-microglobulin were similar in all three experimental groups. In conclusion, we showed that in a DM-IOL animal model, CAP reduced renal iron deposits and increased the level of circulating hepcidin.

Effects of Chronic Administration of Capsaicin on Biomarkers of Kidney Injury in Male Wistar Rats with Experimental Diabetes.

Capsaicin is an agonist of the transient receptor potential vanilloid type 1 (TRPV1) channel, which has been related to the pathophysiology of kidney disease secondary to diabetes. This study aimed to evaluate the chronic effect of capsaicin administration on biomarkers of kidney injury in an experimental rat model of diabetes. Male Wistar rats were assigned to four groups: (1) healthy controls without diabetes (CON), (2) healthy controls plus capsaicin at 1 mg/kg/day (CON + CAPS), (3) experimental diabetes without capsaicin (DM), and (4) experimental diabetes plus capsaicin at 1 mg/kg/day (DM + CAPS). For each group, 24-h urine samples were collected to determine diuresis, albumin, cystatin C, ß2 microglobulin, epidermal growth factor (EGF), alpha (1)-acid glycoprotein, and neutrophil gelatinase-associated lipocalin (NAG-L). Blood samples were drawn to measure fasting glucose. After 8 weeks, the CON + CAPS and DM + CAPS groups showed increased diuresis compared to the CON and DM groups, but the difference was significant only in the DM + CAPS group. The two-way ANOVA only showed a statistically significant effect of CAPS on the urinary EGF levels, as well as a tendency to have a significant effect in the urinary NAG-L levels. The EGF levels decreased in both CAPS-treated groups, but the change was only significant in the CON + CAPS group vs. CON group; and the NAG-L levels were lower in both CAPS-treated groups. These results show that capsaicin had a diuretic effect in healthy and diabetic rats; additionally, it increased the urinary EGF levels and tended to decrease the urinary NAG-L levels.

Nitric oxide in the commissural nucleus tractus solitarii regulates carotid chemoreception hyperglycemic reflex and c-Fos expression.

Carotid body chemoreceptors function as glucose sensors and contribute to glucose homeostasis. The nucleus tractus solitarii (NTS) is the first central nervous system (CNS) nuclei for processing of information arising in the carotid body. Here, we microinjected a nitric oxide (NO) donor sodium nitroprusside (SNP), an NO-independent activator of the soluble guanylyl cyclase (sGC) (YC1) or an NO-synthase (NOS) inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) into the commissural NTS (cNTS) before carotid chemoreceptor anoxic stimulation and measured arterial glucose and the expression of Fos-like immunoreactivity (Fos-ir). Male Wistar rats (250-300 g) were anesthetized, and the carotid sinus was vascularly isolated. Either artificial cerebrospinal fluid (aCSF), SNP, YC1 or L-NAME were stereotaxically injected into the cNTS. The SNP and YC1 infused into the cNTS before carotid chemoreceptor stimulation (SNP-2 and YC1-2 groups) similarly increased arterial glucose compared to the aCSF-2 group. By contrast, infusion of L-NAME into the cNTS before carotid chemoreceptor stimulation (L-NAME-2 group) decreased arterial glucose concentration. The number of cNTS Fos-ir neurons, determined in all the groups studied except for YC1 groups, significantly increased in SNP-2 rat when compared to the aCSF-2 or SNP-2 groups. Our findings demonstrate that NO signaling, and the correlative activation of groups of cNTS neurons, plays key roles in the hyperglycemic reflex initiated by carotid chemoreceptor stimulation.

Influence of cytokine and intercellular adhesion molecule-1 gene polymorphisms on acute rejection in pediatric renal transplantation.

Immune response regulation by cytokines is a key to understanding AGR. The influence of the functional polymorphisms in genes coding for TNF-alpha (-308G > A), IL-10 (-819C > T, and -1082A > G), IFN-gamma [(CA)n], TGF-beta1 (+869T > C), and iCAM-1 (R241G and E469K), in addition to HLA and gender matching on the presentation of AGR in 51 pediatric renal recipients during a 36-month post-transplantation follow-up were analyzed. Also, donors and a control group were genotyped. All groups were within Hardy-Weinberg equilibrium for all polymorphisms except IL-10-819C > T and TNF-alpha (p < 0.005 and p < 0.01, respectively) in recipients. Transplants with gender mismatch showed a higher risk for AGR than those between individuals with gender match (OR, 4.227; p = 0.010). Recipients with a high-production compared with low-production TNF-alpha allele experienced earlier AGR (p = 0.030), and those with high-production alleles of both TNF-alpha and IFN-gamma showed a further increased risk (OR = 11.129, p = 0.024). These findings support the notion that a single genotype cannot by itself explain an event as complex as AGR. The sum or combination of different specific alleles of these genes could better account for the immune response to an allograft.

Melatonin ameliorates renal ischemia/reperfusion injury.

BACKGROUND: We studied whether melatonin is able to reduce organ damage during renal ischemia/reperfusion via its effects on the oxidative response in early and late reperfusion. MATERIALS AND METHODS: Renal ischemia/reperfusion injury (I/R) was induced in two groups of rats by 75 min occlusion of the left renal artery and vein and right nephrectomy, followed by reperfusion. The formation of reactive oxygen species was evaluated in the early reperfusion phase (60 min) by lipid peroxidation products and glutathione assay. In the late reperfusion phase (24 h) tissue neutrophil infiltration, inducible nitric oxide synthase (iNOS) gene expression, and histopathology were evaluated. Groups received either systemic melatonin (MEL) or normal saline (NS). There were two nonischemic sham control groups, one with and another without melatonin (S+MEL and S). RESULTS: Creatinine was higher in the NS group at all times. A reduction in glutathione and increases in lipid peroxidation products and myeloperoxidase activity induced by I/R indicated renal injury involving reactive oxygen formation. Melatonin reversed this oxidant response and reduced the rise in creatinine and iNOS expression. Seven-day group survivals were 5/10 for NS, 8/10 for MEL, and 10/10 for both Sham groups. CONCLUSIONS: Exogenous melatonin is able to preserve renal functional status following I/R-induced injury by increasing glutathione and reducing lipid peroxidation in the early reperfusion phase, without any apparent effect on neutrophil infiltration in the late reperfusion phase.