n-benzoylalanine and Body-Weight

The protective effects of betamipron (BP, N-benzoyl-beta-alanine) on the nephrotoxicity of cisplatin were examined as indicated by body weight gain, ratio of kidney weight to body weight, blood urea nitrogen and serum creatinine levels in tumor-bearing rats. The results showed clearly that administration of BP 1 h after cisplatin treatment affords protection against the nephrotoxicity of cisplatin. Furthermore, the addition of BP to cisplatin had no apparent effect on the efficacy of cisplatin against Walker 256 carcinosarcoma cells in rats. In addition, no observed significant difference in plasma cisplatin concentration between cisplatin with alkaline solution and cisplatin with BP may be partly attributed to the decrease in the cisplatin exsorption to the intestine and its excretion to bile, and to an increase in cisplatin excretion to the urine.

Topics: Alanine; Animals; Antineoplastic Agents; Bile; Blood Urea Nitrogen; Body Weight; Carcinoma 256, Walker; Cisplatin; Creatinine; Drug Antagonism; Intestines; Kidney; Male; Organ Size; Rats; Rats, Wistar

Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the damage observed in the kidney is localized to the proximal tubule cells, we investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cisplatin treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity, increase and subsequent decrease in gamma-glutamyl transferase activities, and increase in beta 2-microglobulin level observed after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.

Topics: Acetylglucosaminidase; Alanine; Animals; Antineoplastic Agents; beta 2-Microglobulin; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; gamma-Glutamyltransferase; Kidney; Kidney Glomerulus; Kidney Tubules; Leukemia P388; Male; Mice; Rats; Rats, Wistar

Prophylactic effects of N-benzoyl-beta-alanine (betamipron, BP), one of a series of N-acyl amino acids, were examined against cisplatin-induced nephrotoxicity. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with an i.p. BP dose given at various times and various doses. Rats were sacrificed 5 days after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Preliminary results suggest that treatment with BP is an effective means of protection against cisplatin-induced nephrotoxicity. Combination with BP reduced the weight loss following treatment with cisplatin. The ratios of the kidney and liver weights to the body weight in the animals treated with cisplatin followed later with BP are significantly different (p < 0.05) from those in the animals that received only cisplatin. The BUN and serum Cr levels in the animals treated with cisplatin followed from -1 to 4 hr, and from -4 to 4 hr later with 250 mg/kg BP dose and followed 1 hr later with from 250 to 1000 mg/kg, and from 250 to 2000 mg/kg BP doses differed significantly (p < 0.05) from those in the animals that received only cisplatin. Histological analysis of the kidneys confirmed the protective effect of BP.

Topics: Alanine; Animals; Antineoplastic Agents; Body Weight; Cisplatin; Drug Evaluation, Preclinical; Kidney; Liver; Male; Organ Size; Random Allocation; Rats; Rats, Wistar; Time Factors

The protective effects of N-benzoyl amino acids (NAAs) and piperacillin (PIP), anionic transport inhibitors, against the nephrotoxicity of cisplatin were examined in rats. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with i.p. NAAs or PIP. Rats were sacrificed on day 5 after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Treatments with NAAs were an effective means of protection against cisplatin-induced nephrotoxicity. The combination of cisplatin with NAAs containing a short and straight chain significantly suppressed (p < 0.05) the changes in body, kidney and liver weights, BUN and serum Cr. Further, betamipron (BP) at a 2000 mg/kg dose showed no apparent effect on the body, kidney and liver weights, BUN and serum Cr levels in rats. The combination of cisplatin with PIP caused a loss in body weight. The protective effects of PIP against cisplatin toxicity are inferior to those of BP when compared at 250 mg/kg doses.

Topics: Alanine; Animals; Antineoplastic Agents; Blood Urea Nitrogen; Body Weight; Cisplatin; Creatinine; Kidney; Liver; Male; Organ Size; Piperacillin; Rats; Rats, Wistar