The aim if this study was to evaluate the effect of sodium overload on blood pressure and renal function in the offspring of diabetic rat mothers. Diabetes was induced with a single dose of streptozotocin before mating. Experimental groups were control (C), offspring from diabetic mother (D), control with sodium chloride (NaCl) overload (CS), and offspring from diabetic mother submitted to NaCl overload (DS). After weaning, all groups received food ad libitum; groups C and D had water ad libitum, and CS and DS received NaCl 0.15 M as drinking water. Renal morphology and function were evaluated in 3-month-old rats. Glomerular area, macrophage infiltration, interlobular artery wall thickness, and renal vascular resistance were significantly increased in CS, D, and DS compared with C. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were decreased in CS and D compared with C. In DS, GFR and fractional filtration were increased, suggesting a state of hyperfiltration. Hypertension was observed in groups D, CS, and DS from 2 months on and was more severe in DS. Our data suggest that diabetes during intrauterine development and salt overload beginning at an early age can cause hypertension and renal injury. When these conditions were associated, morphological and functional changes were much more intense, suggesting acceleration in the process of kidney injury.
The goal in transplantation is to obtain immunosuppressant combinations that decrease the incidence of acute and chronic rejection but cause fewer side effects. FTY720 is a new immunomodulator that prevents experimental allograft rejection without inhibiting T-cell activation. It is currently under clinical investigation for multiple sclerosis. We investigated whether FTY720 in combination with sirolimus (SRL) could cause renal toxicity in C57BL/6 mice when administered for 21 days. Serum creatinine and 24-hour urinary creatinine concentrations were assessed by enzymatic colorimetric assays. Urinary protein concentration was measured by the Bradford protein assay. Whereas serum creatinine levels were increased in FTY720 + SRL-treated animals, there were no changes in urinary volume, urinary protein levels, serum urea concentration, creatinine clearance, and kidney structure. Our findings suggested that FTY720 monotherapy for multiple sclerosis and other diseases could play an important immunomodulatory role without causing the side effects frequently observed with other transplantation regimens.
This study investigated the beneficial effects of D-α-tocopherol supplementation in protecting against the renal morphological and functional changes caused by hypertension. Spontaneously hypertensive (SHR) and normotensive control (WKY) rats received D-α-tocopherol (80 mg/kg by gavage) or vehicle (mineral oil) every other day for 60 days, from the age of 2 months. After this treatment period, all animals were assessed for renal morphological and functional parameters. The glomerular hypertrophy, increased interlobular wall thickness and enlarged renal vascular resistance found in SHR were reduced by D-α-tocopherol treatment. Sodium and volume retention observed in SHR were also decreased by D-α-tocopherol treatment. Moreover, D-α-tocopherol supplementation significantly reduced arterial pressure in SHR but not in WKY. D-α-tocopherol also reduced the excretion of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress, in SHR. These results suggest that D-α-tocopherol supplementation can reduce kidney damage induced by hypertension.
This work was designed to study the effect of L‐Arginine (Arg) treatment on renal morphology changes after unilateral ureteral obstruction (UO). Ureteral obstruction was performed by ligation of the left ureter of Male Wistar rats, 3 month old. Four experimental groups were studied: control‐sham operated: C; obstructed: UO; control treated with Arg: CA; obstructed treated with Arg: UOA. Groups CA, and UOA received as drinking water a solution containing arginine 1% and sucrose 1%, since 24 hours before surgery until 14 days of obstruction, when the animals were studied. The groups C and UO received 1% sucrose solution. We studied: glomerular morphology, alpha smooth muscle actin (α‐SMA) expression, macrophage infiltration (ED1), proliferating cell nuclear antigen (PCNA) expression and fibrosis. We observed that 14 days after UO, α‐SMA expression and macrophage infiltration (ED1) were increased in UO kidney. In OUA, both α‐SMA expression and ED1 presence were reduced. Glomerular hypertrophy was observed in contralateral kidney from UO rats. The treatment with Arg also reduced this response. These results indicate that L‐arginine supplementation has a beneficial effect on renal morphological changes caused by ureteral obstruction.Supported by FAPESP, CAPES, CNPq.
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