Modification of cisplatin toxicity by antioxidants.

Modification of cisplatin toxicity by antioxidants.

Sugihara K, Gemba M. Jpn J Pharmacol. 1986 Feb;40(2):353-5.
cis-Diamminedichloroplatinum II (cisplatin) is a potent anticancer chemotherapeutic agent. The major limitation in its use is nephrotoxicity, caused by an unknown mechanism. Injection of cisplatin into rats caused a decrease in body weight and an increase in blood urea nitrogen (BUN). These effects were modified by giving a radical scavenger, alpha-tocopherol, before the cisplatin injection. N-N’-diphenyl-p-phenylenediamine, another powerful radical scavenger, also attenuated the increase in BUN induced by cisplatin. These results suggest that the toxic effects of cisplatin may be related to free radical induced damage.

In Vitro and In Vivo Effects of Phenolic Antioxidants against Cisplatin-Induced Nephrotoxicity

Rao M, Kumar MM, Rao MA. J Biochem (1999) 125 (2): 383-390.
We have investigated the effect of phenolic antioxidants on cisplatin-induced cytotoxicity in vero (African Green Monkey Kidney) cells and in rat renal cortical slices in vitro, and on cisplatin-induced nephrotoxicity in rats in vivo. Incubation of cisplatin with vero cells resulted in time- and concentration-dependent cytotoxicity, as characterized by decreased tryphan blue exclusion (TBE) and increased release of lactate dehydrogenase (LDH) into the medium. Cisplatin also caused reduction of glutathione (GSH) in a concentration-dependent manner. In the rat renal cortical slices model, incubation of cisplatin for 120 min caused an increase in malondialdehyde (MDA), a decrease in GSH and inhibited p-aminohippurate (PAH) uptake in a concentration-dependent manner. Among phenolic antioxidants, iso-eugenol (IG) was found to be more active against cisplatin-induced cytotoxicity in vero cells as well as in rat renal cortical slices than eugenol (EG) and dehydrozingerone (DZ). However none of the test compounds were able to arrest the reduction of the GSH content induced by cisplatin in either the vero cells or the renal cortical slice model. Administration of cisplatin (3 mg/kg) i.p. to rats resulted in significant reduction of body weight, and elevation of blood urea nitrogen (BUN) and serum creatinine. Treatment with IG 10 mg/kg i.p. 1 h before cisplatin resulted in partial but significant protection against the cisplatin-induced reduction of body weight, and elevation of BUN and serum creatinine, the protection being 34,46, and 62%, respectively. EG and DZ (10 mg/kg, i.p.) were found to be inactive in vivo. Because IG is a potent free radical scavenger and protects against cisplatin-induced toxicitiy, the present results have many clinical implications in cisplatin chemotherapy and thus warrants further investigation.

You can leave a response, or trackback from your own site.

Leave a Reply

You must be logged in to post a comment.