Effect of crempphor- el on cisplatin- induced organ toxity in nor-mal rat

الملخص EN

Cisplatin in an inorganic platinum compound with a broad spectrum antineoplastic activity against different types of tumours.

Pharmacological and cytogenetic evaluations of the possible protective effects of cremophor-EL (cremophor) against cisplatin-induced nephro-, hepato-and bone marrow toxicity in normal rats were carried out.

A single dose of cisplatin (7.5 mg / kg i.v.) caused acute nephrotoxicity biochemically manifested as an increase in serum urea nitrogen (528 %) and serum creatinine (1307 %).

Serum alanine and aspartate aminotransferase levels were also increased.

In the liver tissue, glutathione level (GSH) decreased significantly 7 days after cisplatin treatment.

Cisplatin caused a significant increase in the frequency of micronuclei (MN) of polychromatic eryth-rocytes (PCEs) and norm chromatic erythrocytes (NCEs), as well as the ratio of PCEs/NCEs.

Moreover, a significant delay in the mitotic activity was observed after cisplatin treatment.

Administration of cremophor at a dose of 50 µl/ kg intravenously 5 minutes before cisplatin protected the kidney and liver as indicated by restoration of urea and cretonne concentrations, as well as aminotransferase activities.

Pretreatment with cremophor resulted in a significant recovery in the frequency of cisplatin-induced increase in MV, in the ratio of PCEs / NCEs, as well as in the MI of bone marrow.

Administration of cremophor before cisplatin did not interfere with the antitumour activity of cisplatin in EAC-bearing mice.

These results suggest that cremophor administration may play a role to prevent cis-platin-induced damage to the kidney, liver and bone marrow without interfering with its antitumour activity.