Effects of chronic administration of doxorubicin on plasma levels of prostaglandins, thromboxane B2, and fatty acids in rats.

The effects of multiple doses of doxorubicin (DXR) on hematocrit and plasma levels of prostaglandins (PG), thromboxane B2 (TxB2), total lipid, esterified and free fatty acids, and proteins were investigated in male rats. The rats received DXR (2 mg/kg) or vehicle weekly by the subcutaneous route for 2, 4, 8, and 13 weeks and were killed 1 week after their last dose. Another group of rats treated for 13 weeks was sacrificed at 19 weeks, 6 weeks after the last dose. No changes in hematocrit or plasma PG, TxB2, or total levels of fatty acids were noted between control and DXR-treated rats at either 3, 5, or 9 weeks. The hematocrit was slightly depressed from control levels at 14 and 19 weeks. Plasma PGE, PGF2 alpha, and TxB2 were elevated over control levels at 14 and 19 weeks. Plasma 6-keto-PGF1 alpha was increased over the control level only at 19 weeks. Total plasma lipid and esterified fatty acids were highly elevated over control levels at 14 and 19 weeks. Plasma free arachidonic acid was elevated over control levels at 14 and 19 weeks, while levels of other free fatty acids were unchanged. Plasma protein levels were slightly depressed from control levels at 3, 9, and 14 weeks. Elevations of plasma free arachidonic acid, PG, TxB2, esterified fatty acids, and total lipid might be involved in cardiotoxicity and nephrotoxicity found with chronic administration of DXR.