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[An experimental study of the protective effect of lazaroid (U-74389G) on cisplatin-induced toxicity].
Nihon Jibiinkoka Gakkai Kaiho. 1999 Jan; 102(1):8-18.NJ

Abstract

Lazaroids, a novel series of 21-aminosteroids without glucocorticoid action, have the properties of free radical scavenging and potent inhibition of lipid peroxidation. U-74389G is one of the Lazaroid compounds. These compounds have shown excellent effect on central nervous system trauma and ischemia in experimental animals. The present study was designed to investigate whether Lazaroid (U-74389G) has a protective effect on Cisplatin (CDDP)-induced toxicity. Fisher 344 rats were used in this study. The animals were divided into three groups: I) CDDP 0.9 mg/kg i.v. alone; II) CDDP 0.9 mg/kg i.v. 1 hr after the p.o. administration of U-74389G 10 mg/kg; III) physiological saline 2.5 ml/kg i.v. instead of CDDP, for 7-10 days. First, the protective effect of Lazaroid (U-74389G) on CDDP-induced ototoxicity was studied. Cochlear damage was evaluated by means of the compound action potential (CAP) and histological examination using scanning electron microscopy. The degree of elevation of CAP thresholds and the rate of missing outer hair cells were significantly reduced in Group II as compared to Group I. These results clearly demonstrate that Lazaroid (U-74389G) has a protective effect on CDDP-induced ototoxicity. Second, the protective effect of Lazaroid (U-74389G) on CDDP-induced nephrotoxicity was studied. Nephrotoxicity was evaluated by means of serum BUN level and histopathological examination. There was no significant difference in serum BUN level and little difference of renal histopathological findings between Group I and Group II. Lazaroid (U-74389G) was not found to ameliorate CDDP-induced nephrotoxicity. Third, the influence of Lazaroid (U-74389G) on the antitumor effect of CDDP was investigated in rats inoculated subcutaneously with SCC-158 squamous-cell carcinoma cells. There was no significant difference of Tumor Growth Rate (TGR) between Group I and Group II. The result suggests that the combined administration does not alter the antitumor activity of CDDP. In conclusion, the combined administration of CDDP with Lazaroid (U-74389G) ameliorates CDDP-induced ototoxicity without decreasing the antitumor activity of CDDP.

Authors+Show Affiliations

Department of Otolaryngology, Fukushima Medical University School of Medicine.No affiliation info available

Pub Type(s)

English Abstract
Journal Article

Language

jpn

PubMed ID

10067316

Citation

Hori, H, and H Kanno. "[An Experimental Study of the Protective Effect of Lazaroid (U-74389G) On Cisplatin-induced Toxicity]." Nihon Jibiinkoka Gakkai Kaiho, vol. 102, no. 1, 1999, pp. 8-18.
Hori H, Kanno H. [An experimental study of the protective effect of lazaroid (U-74389G) on cisplatin-induced toxicity]. Nippon Jibiinkoka Gakkai Kaiho. 1999;102(1):8-18.
Hori, H., & Kanno, H. (1999). [An experimental study of the protective effect of lazaroid (U-74389G) on cisplatin-induced toxicity]. Nihon Jibiinkoka Gakkai Kaiho, 102(1), 8-18.
Hori H, Kanno H. [An Experimental Study of the Protective Effect of Lazaroid (U-74389G) On Cisplatin-induced Toxicity]. Nippon Jibiinkoka Gakkai Kaiho. 1999;102(1):8-18. PubMed PMID: 10067316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [An experimental study of the protective effect of lazaroid (U-74389G) on cisplatin-induced toxicity]. AU - Hori,H, AU - Kanno,H, PY - 1999/3/6/pubmed PY - 1999/3/6/medline PY - 1999/3/6/entrez SP - 8 EP - 18 JF - Nihon Jibiinkoka Gakkai kaiho JO - Nippon Jibiinkoka Gakkai Kaiho VL - 102 IS - 1 N2 - Lazaroids, a novel series of 21-aminosteroids without glucocorticoid action, have the properties of free radical scavenging and potent inhibition of lipid peroxidation. U-74389G is one of the Lazaroid compounds. These compounds have shown excellent effect on central nervous system trauma and ischemia in experimental animals. The present study was designed to investigate whether Lazaroid (U-74389G) has a protective effect on Cisplatin (CDDP)-induced toxicity. Fisher 344 rats were used in this study. The animals were divided into three groups: I) CDDP 0.9 mg/kg i.v. alone; II) CDDP 0.9 mg/kg i.v. 1 hr after the p.o. administration of U-74389G 10 mg/kg; III) physiological saline 2.5 ml/kg i.v. instead of CDDP, for 7-10 days. First, the protective effect of Lazaroid (U-74389G) on CDDP-induced ototoxicity was studied. Cochlear damage was evaluated by means of the compound action potential (CAP) and histological examination using scanning electron microscopy. The degree of elevation of CAP thresholds and the rate of missing outer hair cells were significantly reduced in Group II as compared to Group I. These results clearly demonstrate that Lazaroid (U-74389G) has a protective effect on CDDP-induced ototoxicity. Second, the protective effect of Lazaroid (U-74389G) on CDDP-induced nephrotoxicity was studied. Nephrotoxicity was evaluated by means of serum BUN level and histopathological examination. There was no significant difference in serum BUN level and little difference of renal histopathological findings between Group I and Group II. Lazaroid (U-74389G) was not found to ameliorate CDDP-induced nephrotoxicity. Third, the influence of Lazaroid (U-74389G) on the antitumor effect of CDDP was investigated in rats inoculated subcutaneously with SCC-158 squamous-cell carcinoma cells. There was no significant difference of Tumor Growth Rate (TGR) between Group I and Group II. The result suggests that the combined administration does not alter the antitumor activity of CDDP. In conclusion, the combined administration of CDDP with Lazaroid (U-74389G) ameliorates CDDP-induced ototoxicity without decreasing the antitumor activity of CDDP. SN - 0030-6622 UR - https://www.unboundmedicine.com/medline/citation/10067316/[An_experimental_study_of_the_protective_effect_of_lazaroid__U_74389G__on_cisplatin_induced_toxicity]_ L2 - http://www.medicalonline.jp/meteo_linkout.php?issn=0030-6622&volume=102&issue=1&spage=8 DB - PRIME DP - Unbound Medicine ER -