Abstract
The present study is aimed to examine the possible effects of Protein Malnutrition (PM) on the therapeutic activity and toxicity of paclitaxel in mice implanted with Ehrlich carcinoma cells. Mice that were fed either with standard or low protein diets were treated with a single dose of paclitaxel (10 mg kg(-1), i.p.). Paclitaxel administration increased the tumor growth delay of Ehrlich carcinoma from 2.8 days in protein deficient animals to 4.9 days in normal feeding mice and this represented about 43% increase in tumor growth delay. Furthermore, protein deficiency also interfered with the antitumor activity of paclitaxel. The percent survival of tumor-bearing mice after paclitaxel treatment were 56 and 19% in normal fed and protein deficient animals, respectively. Moreover, Paclitaxel administration increased the serum level of creatine phosphokinase isoenzyme (CPK-MB) in both groups, with maximum effect appeared after 48 h. Seventy two hours later, the levels was reduced to the normal values in normal fed animals while in protein malnourished mice, the activity was found to be high. In addition, paclitaxel administration significantly increased the plasma histamine concentration after 10 min and persisted for 120 min in animals on protein malnourished diet, however, in animals on a normal fed diet, histamine concentration reached the normal level after 120 min of paclitaxel administration. In conclusion, Paclitaxel administration exerts its toxic effects on both protein malnourished- and normal feeding animals, however, its toxicity is enhanced and therapeutic activity is reduced in the protein deficient animals.