Protective Effect ofN-Benzoyl-β-Alanine Against Cisplatin Nephrotoxicity in Rats

Abstract

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.

Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs)

“…Analysis of metabolites most significantly changed upon cisplatin treatment in the endometabolome of iRECs uncovered substances, to which beneficial effects against cisplatin-induced nephrotoxicity have been attributed. These included taurine, pyridoxine and beta-alanine (the latter administered as N-benzoyl-beta-alanine) 63 – 65 . In summary, our findings suggest that iRECs faithfully reflect many pathophysiological responses to cisplatin.…”

Analysis of Renal Platinum Content as a Novel Approach to Protect against Cisplatin Nephrotoxicity: A Review

“…It was proposed that the cytoprotective effect of neutral small amino acids is attributed to their ability to influence the tertiary protein structure of renal cell membranes. They could be accumulated within the cell without disrupting pH or binding to reactive sites on intracellular proteins, and so they would correct the membrane-damaging actions of cytotoxic agents [137].…”

“…In the last years, certain amino acids have been shown to prevent CDDP-induced nephrotoxicity in vivo: L-cysteine [138], L-methionine [139]), Nacetylcysteine [126], glycine [140], L-arginine [141], N-benzoyl-b-alanine [137] and glutamine [142]. However, the nephroprotective mechanisms are not well understood.…”

Evaluation of a Short-term Rat Proximal Tubule Incubation System for the Detection of Nephrotoxicants

“…The compound can be retained in the kidney for days after a single dose. It is taken up by renal tubular cells, and becomes concentrated in the proximal tubular cells of the inner cortex and outer medulla (33). Cytotoxicity might result from a combination of peroxidation of the cell membrane, mitochondrial dysfunction, inhibition of protein synthesis, and DNA injury, with the precise (34).…”