Steviol effect, a glycoside of Stevia rebaudiana, on glucose clearances in rats / O efeito do esteviol, um glicosídeo da Stevia rebaudiana, no clearance da glicose em ratos

Stevia rebaudiana, a South American plant normally used as a natural herbal sweetener, has been suggested as exerting beneficial effects on human health, including as an antihypertensive and antihyperglycemic. The present experiment was undertaken to evaluate the renal excretion of steviol, the aglycone of several natural products extracted from the leaves of S. rebaudiana, and to clarify the actual participation of this compound on the renal excretion of glucose in rats, which has been previously suggested as the preferential action of steviol on the Na+-glucose renal tubular transport system. Steviol was obtained by enzymatic hydrolysis of stevioside with pectinase. Thirty normal male Wistar rats weighing 345 g were used. After a control period, steviol was infused iv at three doses (0.5, 1.0 and 3.0 mg.kg-1/h), according to classical clearance techniques. During all the experiments no significant changes in inulin clearance (Cin) and p-aminohipuric acid clearance (C PAH) were observed. Administration of steviol resulted in a statistically significant increase in the fractional sodium excretion (FeNa+), fractional potassium excretion (FeK+), urinary flow as percent of glomerular filtration rate (V/GFR) and glucose clearance (C G) when compared to controls, but these effects were absent with the dose of 0.5 mg.kg-1/h. The steviol clearance (C S) was higher than the Cin and lower than the C PAH at all the doses employed in this study. The data suggest that steviol is secreted by renal tubular epithelium, causing diuresis, natriuresis, kaliuresis and a fall in renal tubular reabsorption of glucose.

Stevia rebaudiana, uma planta da América do Sul usada como adoçante natural, parece exercer efeitos benéficos para a saúde humana, incluindo ação anti-hipertensiva e anti-hiperglicêmica. No presente trabalho objetivamos avaliar a excreção renal do esteviol, uma aglicona extraída das folhas de S. rebaudiana, e elucidar a participação deste composto na excreção renal de glicose em ratos, o qual foi sugerido agir no sistema de transporte tubular renal Na+-glicose. O esteviol foi obtido por hidrólise enzimática com pectinase. Foram usados 30 ratos Wistar machos e pesando 345 g. Após um período controle, o esteviol foi infundido iv em três doses (0,5, 1,0 e 3,0 mg.kg-1/h) de acordo com técnicas clássicas de clearance. Durante os experimentos não houve alterações significantes no clearance da inulina (Cin) e do ácido-aminohipúrico (C PAH). A administração de esteviol resultou em um aumento estatisticamente significante na excreção fracional de sódio (FeNa+) e potássio (FeK+ ), no fluxo urinário como porcentagem da taxa de filtração glomerular (V/GFR) e do clearance de glicose (C G) quando comparados aos animais controles, embora estes efeitos estivessem ausentes na dose de 0,5 mg.kg-1/h. O clearance de esteviol (C S) foi maior que o Cin e menor que o C PAH em todas as doses usadas nos experimentos. Os dados sugerem a secreção de esteviol pelo epitélio tubular renal, causando diurese, natriurese, caliurese e uma redução na reabsorção tubular renal de excreção de glicose.

Effect of strenuous maternal exercise before and during pregnancy on rat progeny renal function

The effects of strenuous exercise before and during pregnancy on the renal function and morphological alterations of the progeny were determined in a study on female Wistar rats. This research was done based on a previous study carried out in our laboratory, which showed morphological alterations in rats submitted to this kind of exercise. As the form is related to the function, the physiological relevance of submitting a pregnant female to a high-intensity exercise training regimen could be explained by the fact that morphological alterations can influence kidney function. The animals were assigned to one of two groups: control animals that did not exercise during pregnancy and trained animals that swam for 120 min 5 days a week for 8 weeks before pregnancy and daily for 60 min over a period of 8 weeks starting on the second day of pregnancy. Seven rats of each group were analyzed for morphological alterations and for renal function. The progeny of the rats used for morphological evaluation were born by cesarean section and the progeny of the animals used to evaluate renal function were born normally. The progeny were two months old when renal function was evaluated. Fertility and morbidity were the same for both groups. Strenuous maternal exercise had no significant influence on glomerular filtration rate (GFR) but renal plasma flow was lower in the progeny of the trained group (mean ñ SD, 16.65 ñ 3.77 ml min-1 kg-1) compared to the progeny of the control group (33.42 ñ 2.56 ml min-1 kg-1). Antidiuretic and antinatriuretic effects on the progeny of the trained group were observed, since urine flow as percentage of GFR and the fraction of urinary sodium excretion were lower in this group (1.38 ñ 0.10 and 0.60 ñ 0.04 percent, respectively) compared to the progeny of the control group (2.36 ñ 0.11 and 1.55 ñ 0.20 percent, respectively). Moreover, in this exercise program, fetuses from trained animals were small-sized (2.45 ñ 0.19 vs 4.66 ñ 2.45 g for control animals) and showed lower differentiation compared to fetuses from the control group. These effects were probably caused by caloric restriction, hypoxia and reduction of umbilical cord length.

A crude extract of Stevia rebaudiana increases the renal plasma flow of normal and hypertensive rats

The effect of S. rebaudiana extract on renal function was evaluated in normotensive and in experimental renal hypertensive rats (GII) using clearance techniques. Experiments were performed on male Wistar rats weighing 300-330 g (10 animals per group). Goldblatt GH experimental hypertension was induced by placing a silver clip with an internal gap of 0.25 mm around the left renal artery under ether anesthesia. The contralateral kidney was left untouched. Stevia was administered 1012 weeks after clipping. Oral administration of Stevia extract, corresponding to 2.67 g dry leaves/day for 30 days, resulted in a significant decrease in mean arterial pressure in both the normo- (N) and hypertensive rats (H) (N rats: 113 ñ 3.0 mmHg in the control (C) group vs 69.5 ñ 4.0 mmHg in the Stevia (S) group; H rats: 155 ñ 3.0 mmHg in C vs 108 ñ 4.0 mmHg in S; P<0.05). Glomerular flltration rate was constant in the N rats and increased significantly in the H rats afterStevia treatment (6.47 ñ 1.29 vs 14.2 ñ 1.33 ml min-1 kg-1 in the C and S groups, respectively, P<0.05). Normo- and hypertensive rats presented an increase in renal plasma flow following oral Stevia administration (N rats: 16.4 ñ 3.10 ml min-1 kg-1 in the C group vs 33.3 ñ 3.20 ml min-1 kg-1 in the S group,P<0.05; H rats: 19.30ñ2.45 ml min-lkg-1 in the C group vs 37.0 ñ 3.93 ml min-1 kg-1 in the S group, P<0.05). Stevia administration provoked an increase in urinary flow in both N and H animais (1.37 ñ O.08 per cent vs 2.32 ñ 0.11 per cent P<0.05 and 1.47 ñ 0.07 per cent vs 2.96 ñ O.13 per cent, P<0.05 in N and H rats, respectively). Sodium excretion increased in N and H animals after Stevia treatment (N rats: O.61 ñ O.07 per cent in the C group vs 1.55 ñ 0.20 per cent in the S group, P<0.05; H rats: 0.70 ñ 0.1O per cent in the C group vs 2.22 ñ O.45 per cent in the S group, P<0.05). These results are consistent with impairtnent of a renal autoregulation mechanism in this hypertensive model after Stevia administration. In conclusion, it was shown that Stevia extract, at doses higher than used for sweetening purposes, is a vasodilator agent in - and hypertensive animals.

Influence of calcium on the blood pressure and renal effects of stevioside

The effect of verapamil (V, 0.015 mg/min, iv) or Ca Cl2 (800 mEq/l, 0.025 ml kg-1 min-1,iv) on renal function and mean arterial pressure (MAP) were evaluated in male Wistar rats weighing 280-320 g during treatment with stevioside (S, 16 mg kg-1 h-1, iv). Verapamil administered to 10 rats significantly increased the hypotensive effect of stevioside on MAP (control 124 ñ 0.77; S, 96 ñ 1.50; S+V, 67 ñ 0.70 mm Hg) and fractional sodium excretion (control 0.76 ñ 0.05; S, 1.56 ñ 0.10; S+V, 2.72 ñ 0.25%). Urinary flow, reported as percent glomerular filtration rate (V/GRF), and renal plasma flow (RPF) increased slightly but not significantly during stevioside plus verapamil administration. In contrast, infusion of CaCl2 in 10 rats pretreated with stevioside induced a marked attenuation of MAP (control 119 ñ 1.83; S, 70 ñ 1.12; S ñ CaCl2, 109 ñ 1.60 mmHg) and RPF (control, 16.73 ñ 3.76; S, 34.33 ñ 2.55; S+CaCl2, 17.20 ñ 2.87 ml min-1 Kg-1). The diuresis and natriuresis induced by stevioside were also inhibited by simultaneous administration of CaCl2. These data are consistent with the view that stevioside acts on arterial pressure and renal function as a calcium antagonist, as is the case for verapamil

Participation of prostaglandins in the effect of stevioside on rat renal function and arterial pressure

1. The effect if stevuisude ib renal function was evaluated by clearance tecniques in Wistar rats simultaneously with the effect of indomethacin on the renal action of stevioside. The indomethacin experiments consisted of four consectuve periods: (C) control; (S), in which stevioside (16 mg/Kg) was continously infused; (S+I1) and (S+I2) in which indomethacin was infused systemically without interrupting stevioside infusion. Mean arterial pressure (MAP) and renal function perameters were measured. 2. Administration of stevioside resulted in a statistically significant dose-related decrease in MAP (121 ñ 2.30, N = 7 for 4mg/Kg stevioside to 72 ñ 4.79 mmHg, N = 7 for 16 mg/Kg stevioside) and an increase in renal plasma flow (RPF) (10.27 ñ 1.21, N = 7 for 4 mg/Kg stevioside to 26.28 ñ 2.87 ml min-1 Kg-1, N = 7 for 16 mg/Kg stevioside), with no change in glomerular filtration rate (GFR). Stevioside also increased fractional sodium (FeNa+) and potassium (FeK+) excretion as well as urine flow (V/GFR). 3. The decrease in MAP (control, 121 ñ 0.93, N = 7; stevioside, 91 ñ 2.48 mmHg) and increase in RPF (control, 14.21 ñ 1.41, N = 7; stevioside, 32.53 ñ 2.84 mmHg) induced by stevioside (16 mg/Kg) were inhibited by simultaneous administration of indomethacin (2 mg/Kg) but GFR was not affected. The diuretic, natriuretic and kaliuretic effects of stevioside were also abolished by indomethacin. 4. We conclud that stevioside behaves like a typical vasodilator substance, causing changes in MAP, diuresis, natriuresis and kaliuresis per ml of GFR, and these effects probably depend on prostaglandins