Adenine-induced Renal Failure Research Articles

Potentiating effect of converting enzyme inhibitor captopril to the renal responses of magnesium lithospermate B in rats with adenine-induced renal failure.

The renal responses of magnesium lithospermate B were investigated in the presence or absence of pretreatment with the converting enzyme (kininase II) inhibitor, captopril, in rats with adenine-induced renal failure. Magnesium lithospermate B (10 mg/kg body weight) caused a marked increase in the levels of the renal functional parameters (glomerular filtration rate, renal plasma flow and renal blood flow), accompanied by significant increases in urinary excretions of prostaglandin E2 (PGE2), kallikrein, sodium and creatinine. The administration of magnesium lithospermate B in combination with captopril (2 mg/kg body weight, 2 times) caused a further increase in renal functional parameters, urinary sodium and creatinine excretions. However, the kallikrein activity was similar to the control level. There were no significant changes between urinary PGE2 following magnesium lithospermate B alone, or in combination with captopril. In addition, angiotensin converting enzyme activity did not change following the administration of magnesium lithospermate B alone, but was significantly decreased in rats given captopril, both alone and in combination with magnesium lithospermate B. The captopril administration group (captopril alone or in combination with magnesium lithospermate B) showed a significant decrease in blood pressure. From these results, it seems that the combination of magnesium lithospermate B and captopril induces a further increase in renal function by improving the renal circulatory state.

Effects of Rhubarb Tannins on Uremic Toxins

The effects of each of several tannins purified from Rhei Rhizoma on serum constituents were investigated in rats with adenine-induced renal failure. Blood levels of urea nitrogen, methylguanidine (MG), and guanidinosuccinic acid (GSA) were significantly decreased in rats given (-)-epicatechin 3-O-gallate at a dose of 2.5, 5 or 10 mg/kg body weight/day for 24 days. The creatinine (Cr) level was also significantly decreased in rats given 5 and 10 mg of this compound. A significant decrease in urea nitrogen, MG, and GSA was found in rats given 6.25 mg of procyanidin B-2 3,3'-di-O-gallate. However, unlike the former two components the administration of 12.5 mg of procyanidin C-1 3,3',3''-tri-O-gallate produced a considerable or significant increase in bLood levels of urea nitrogen, Cr, MG, and GSA. RG-tannin had a weaker overall effect on serum constituents except for GSA in comparison with the corresponding effect of (-)-epicatechin 3-O-gallate and 6.25 mg of procyanidin B-2 3,3'-di-O-gallate. Rhatannin tended to increase the serum nitrogen constituents.

Production of Methylguanidine from Creatinine in Normal Rats and Rats with Renal Failure

Creatinine (Cr) was administered intraperitoneally to both normal rats and those given adenine, and time-course changes in methylguanidine (MG) production from Cr were compared. In rats with renal failure, the accumulation of MG in the body increased gradually with time after Cr administration. In particular, the MG level in skeletal muscle was markedly high in comparison with that in serum, liver or kidney, and a high concentration of MG was still present 24 h after Cr loading. In contrast, the amount of MG excreted into urine in these rats during 24 h after Cr administration was lower than the corresponding values in normal rats. Thus, the amount of MG per rat, distributed at 24 h after intraperitoneal administration of Cr 300 mg/100 g body weight was calculated. The production of MG from Cr was found to be markedly higher in rats with adenine-induced renal failure (172.09 micrograms/100 g body weight) than in normal rats (70.30 micrograms/100 g body weight). Produced MG was mostly excreted into urine in normal rats, whereas in rats with renal failure as much as 79.1% of produced MG was accumulated in the body.

Contribution of prostaglandins to the renal responses to magnesium lithospermate B isolated from salviae miltiorrhizae radix.

The involvement of prostanoids in the improvement of adenine-induced renal failure in rats by magnesium lithospermate B was studied. After intraperitoneal administration of magnesium lithospermate B to renal failure rats, the levels of glomerular filtration rate, renal plasma flow and renal blood flow were increased. Urinary excretions of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in renal failure rats were increased by the administration of magnesium lithospermate B, while that of thromboxane B2 had no effect. Pretreatment with indomethacin abolished the improving effect of magnesium lithospermate B on renal function concomitantly with markedly suppressed urinary excretion of prostanoids. These results suggest that the increased formation of PGE2 and 6-keto-PGF1 alpha might contribute to the improvement of adenine-induced renal failure in rats by magnesium lithospermate B.

Urine composition in rats with adenine-induced renal failure during treatment with rhubarb extract.

The effect of rhubarb extract on the urinary constituents was examined in rats with renal failure induced by adenine. Administration of the rhubarb extract markedly increased the urinary excretion of both urea and creatinine, indicating an improvement of renal clearance in the uremic state. Furthermore, a number of significant differences in the amino acid levels in the urine were observed. Among the essential amino acids, the urinary outputs of threonine, phenylalanine, leucine, and methionine were remarkably lower in the rhubarb extract-treated group than in the control group. Outputs of inessential amino acids (alanine, glycine, glutamic acid, serine, aspartic acid, tyrosine, and cysteine) were also strikingly reduced after the treatment. In addition. the amount of urinary Ca was significantly reduced in the rhubarb extract-treated rats. while urinary inorganic phosphate was significantly elevated. A marked decrease of 2, 8-dihydroxyadenine excretion in the urine was noticed. However, no changes were seen in the urinary excretions of protein, glucose, Na, and K throughout the experimental period.

Effect of extract from Rhei Rhizoma on adenine-induced renal failure in rats.

The effect of the extract from Rhei Rhizoma was examined in rats with renal failure induced by an adenine diet. On treatment with the rhubarb extract, the level of urea nitrogen and creatinine in the serum showed a significant decrease, indicating an improvement of renal function. The urea concentrations in the liver and kidney were also decreased after the treatment. In addition, administration of the rhubarb extract to rats markedly decreased the kidney weight and 2, 8-dihydroxyadenine content in the kidneys. Macroscopic aspects of the kidneys, such as the appearance of the cut surface, were improved. However, there was no statistically significant difference between the control and rhubarb extract-treated groups with regard to the number of foreign body granulomas and deposits of acicular crystals (2, 8-dihydroxyadenine).