Effect of <i>L</i>-Histidinol on Cisplatin Nephrotoxicity in the Rat

Abstract

The effect of L-histidinol (LHL) on the acute nephrotoxicity produced by cisplatin (CDDP; 6 mg/kg, i.v.) was investigated in the rat. Intraperitoneal administration of LHL (100 mg/kg × 5 doses, 2 h apart) starting 2 h prior to CDDP single injection produced significant protection of renal function. The attenuation of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione-S-transferase (GST) activity, and increased urine/serum creatinine ratio as well as increased creatinine clearance. LHL significantly ameliorated the toxic renal biochemical changes induced by CDDP. Renal lipid peroxides, glutathione levels and GST activity showed a marked tendency towards the normal values. Accumulation of platinum in renal tissues was significantly decreased in the presence of LHL. It is concluded that LHL can act as a nephroprotectant, and it is suggested that it would have beneficial effects on the kidney in clinical settings.

<i>L</i>-Histidinol Attenuates Fanconi Syndrome Induced by Ifosfamide in Rats

“…The finding that LHL attenuates IFO-induced FS in rats is in harmony with the results obtained by Badary et al [14]who demonstrated a protective effect of LHL on cisplatin-induced nephrotoxicity in rats. Moreover, the present data are supported by earlier findings of Edelstein [25]who demonstrated a protective effect of LHL on cisplatin-induced hematopoietic toxicity in mice and those of Sawyer et al [26]who showed that LHL protected mice from fluorouracil-induced toxicity.…”

“…Whether LHL will achieve beneficial effects in the clinical situation remains to be demonstrated. However, the effectiveness of oral LHL against IFO toxicity shown here and the recent prior data suggesting benefit during cisplatin [14]and doxorubicin [13]treatment indicate that further consideration may be given to the clinical application of this approach to reduce the toxicity associated with cancer chemotherapy.…”

“…It improves the selectivity and efficacy of antimetabolites, alkylating agents, and anthracyclines in mice bearing a variety of transplantable tumors [9, 10, 11, 12, 13]. Recently, LHL was shown to protect against cisplatin-induced nephrotoxicity in rats [14]. In the present study, the possibility that LHL may ameliorate IFO-induced FS was evaluated in an established rat model [6].…”

Effect of oral administration of arabic gum on cisplatin‐induced nephrotoxicity in rats

“…The exact mechanism of nephrotoxicity induced by CP is not fully understood and is still controversial, but it has been sometimes associated with renal lipid peroxidation [9]. The period after which a single dose of CP can induce nephrotoxicity in rat model is different ranging from 1 up to 7 days as reported by several investigators [10][11][12][13].…”

“…For example, in animals, melatonin [11], 4-methylthiobenzoic acid [12], L-histidine [10], and the flavonoid silibinin [14] have been shown to reduce CP-induced nephrotoxicity. However, none of them has proven to be clinically effective as a complete protective agent in patients.…”