Effect of D-alpha-tocopherol on tubular nephron acidification by rats with induced diabetes mellitus

The objective of the present study was to determine if treatment of diabetic rats with D-alpha-tocopherol could prevent the changes in glomerular and tubular function commonly observed in this disease. Sixty male Wistar rats divided into four groups were studied: control (C), control treated with D-alpha-tocopherol (C + T), diabetic (D), and diabetic treated with D-alpha-tocopherol (D + T). Treatment with D-alpha-tocopherol (40 mg/kg every other day, ip) was started three days after diabetes induction with streptozotocin (60 mg/kg, ip). Renal function studies and microperfusion measurements were performed 30 days after diabetes induction and the kidneys were removed for morphometric analyses. Data are reported as means ± SEM. Glomerular filtration rate increased in D rats but decreased in D + T rats (C: 6.43 ± 0.21; D: 7.74 ± 0.45; D + T: 3.86 ± 0.18 ml min-1 kg-1). Alterations of tubular acidification observed in bicarbonate absorption flux (JHCO3) and in acidification half-time (t/2) in group D were reversed in group D + T (JHCO3, C: 2.30 ± 0.10; D: 3.28 ± 0.22; D + T: 1.87 ± 0.08 nmol cm-2 s-1; t/2, C: 4.75 ± 0.20; D: 3.52 ± 0.15; D + T: 5.92 ± 0.19 s). Glomerular area was significantly increased in D, while D + T rats exhibited values similar to C, suggesting that the vitamin prevented the hypertrophic effect of hyperglycemia (C: 8334.21 ± 112.05; D: 10,217.55 ± 100.66; D + T: 8478.21 ± 119.81æm²). These results suggest that D-alpha-tocopherol is able to protect rats, at least in part, from the harmful effects of diabetes on renal function.

Effects of dietary lipids on renal function of aged rats

Normal aging is accompanied by renal functional and morphological deterioration and dietetic manipulation has been used to delay this age-related decline. We examined the effects of chronic administration of diets containing 5 percent lipid-enriched diet (LD, w/w) on renal function of rats at different ages. Three types of LD were tested: canola oil, fish oil and butter. Mean systemic tail-cuff blood pressure and glycemia remained within the normal range whatever the age and the diet of the animals. Proteinuria began to rise from the 8th month in the groups ingesting LD, while in the control group it increased significantly (above 10 mg/24 h) only after the 10th month. With age, a significant and progressive decline in glomerular filtration rate (GFR) and renal plasma flow was observed in the LD groups but after 6 months of lipid supplementation, the decline in these parameters was more marked in the butter and fish oil groups. By the 18th month, the lowest GFR level was observed in the group ingesting the butter diet (2.93 + or - 0.22 vs 5.01 + or - 0.21 ml min-1 kg-1 in control, P<0.05). Net acid excretion, evaluated in 9- and 18-month-old rats, was stimulated in the fish oil group when compared both to control and to the other two LD groups. These results suggest that even low levels of LD in a chronic nutritional regimen can modify the age-related changes in renal function and that the impact of different types of lipid-supplemented diets on renal function depends on the kind of lipid present in the diet

Effect of thyroparathyroidectomy on urinary acidification in diabetic rats

In previous studies we have shown stimulation of renal acid excretion in the proximal tubules of rats with diabetes of short duration, with no important alterations in glomerular hemodynamics; on the other hand, in thyroparathyroidectomized rats (TPTX model), a significant decrease in renal acid excretion, glomerular filtration rate (GFR) and renal plasma flow (RPF) was detected. Since important changes in the parathyroid hormone-vitamin D-Ca axis are observed in the diabetic state, the present study was undertaken to investigate the renal repercussions of thyroparathyroidectomy in rats previously made diabetic by streptozotocin (45 mg/kg). Four to 6 days after the induction of diabetes (DM), a group of rats were thyroparathyroidectomized (DM + TPTX). Renal functional parameters were evaluated by measuring the inulin and sodium para-aminohippurate clearance on the tenth day. The decrease in the GFR and RPF observed in TPTX was not reversed by diabetes since the same alterations were observed in DM + TPTX. Net acid (NA) excretion was unchanged in DM (6.19 ± 0.54), decreased in TPTX (3.76 ± 0.25) and returned to normal levels in DM + TPTX (5.54 ± 0.72) when compared to the control group (6.34 ± 0.14 µmol min-1 kg-1). The results suggest that PTH plays an important vasodilator role regarding glomerular hemodynamics, since in its absence the impairment in GFR and RPF was not reversed by the diabetic state. However, with respect to acid excretion, the presence of diabetes was able to overcome the negative stimulus represented by TPTX

Renal effect of gentamicin in diabetic rats

To evaluate the protective effect of diabetes mellitus (DM) on renal function of rats treated with gentamicin (GM), male Wistar-EPM rats (250-350 g) were treated with streptozotocin (SZ; 45 mg/kg) and starting 10 days after induction of diabetes, GM was given for ten consecutive days at a daily dose of 40 mg/kg. In the GM-treated group (G), a significant fall in inulin and sodium-p-aminohippurate clearance was obtained (3.57 + or - 0.16 and 12.59 + or - 0.61 ml min-1kg-1 vs 6.43 + or - 0.21 and 17.98 + or - 0.47 ml min-1 kg-1 in control rats (C), respectively) while in the animals previously injected with SZ (diabetic + gentamicin, DG group) these changes injected with SZ (diabetic + gentamicin, DG group) these changes were not observed. The diabetic (D), g and DG group showed a significant rise in urinary flow compared to C (0.165 + or - 0.009, 0.145 + or - 0.007 and 0.173 + or - 0.009 ml min-1kg-1 vs 0.109 + or - 0.003 ml min-1kg-1, respectively); however, only in G was the U/P inulin ration significantly decreased when compared to C. The fractional excretion (FE) of sodium and postassium was significantly augmented in G when compared to C, D and DG. Thus, diabetes protected against gentamicin nephrotoxicity at both the glomerular and tubular level, although it did not promote a reduction in urinary flow

Effects of parathyroid hormone on urinary acidification in the rat

To evaluate the effects of parathyroid hormone (PTH) on urinary acidification parameters, thyroparathyroidectomy was performed in normal (TPTX) and in calcium-supplemented rats (TPTX+Ca2**). Both groups were supplemented with thyroxin. Glomerular filtration rate (GFR) fell from 7.79 ñ 0.33 in the control group (C) to 4.88 ñ 0.26 ml min**-1Kg**-1 in TPTX, while net acid excretion fell from 5.65 ñ 0.22 in C to 3.76 ñ 0.26 µmol min**1Kg in TPTX. Kinetic dat of urinary acidification obtained by microperfusion techniques in proximal tubules showed that the half-time of acidification (t/2) rose from 4.75 ñ 0.24 s in C to 8.97 ñ 0.64s in TPTX and persisted elevated in TPTx +Ca**2+ (7.40 ñ 0.43s); in the latter group, stationary pH was not significantly different from that of the control group. Bicarbonate reabsorption (J**HCO3) fell from 2.18 ñ 0.15 in C to 0.823 ñ 0.082 in TPTX and was 1.53 ñ 0.073 nmol s**-1 cm**-2 in TPTX+Ca**2+. These suggest that normal pH gradients depend on normal calcium levels, but acidification half-times are dependent on PTH, which also contributes keeping glomerular hemodynamics and acidification rates at normal levels