Effectiveness of the adriamycin-DNA complex in kidney allograft immunosuppression.
The chemotherapeutic effectiveness of the lysosomotropic Adriamycin-DNA complex has been demonstrated experimentally. This study evaluated the immunosuppressive activity of the complex on renal allografts in rats of the Buffalo-Lewis strain. Six rats receiving no treatment served as a control. Five rats received DNA along (at a dose equivalent to that in the complex), seven received the Adriamycin-DNA complex (molar ratio of DNA mononucleotide to Adriamycin, 20:1) and five were given free Adriamycin. Adriamycin, free or linked to DNA, was injected as follows: 2 mg/kg on days 2, 6 and 9 and 1 mg/kg on day 13 after transplantation. The Adriamycin-DNA complex prevented renal allograft rejection in the early postoperative period, by delaying for more than a week, the increase in serum creatinine levels in animals receiving transplants. Histologic examination of renal grafts in these rats confirmed the reduced severity of acute cellular rejection. There was also functional and morphologic evidence of reduced toxicity of Adriamycin when linked to DNA. The beneficial effect of such a drug should be attributed to its lysosomotropic mechanism of activity.
D000818:Animals; D003404:Creatinine / Q000097:blood; D004247:DNA / Q000494:pharmacology*; D018736:DNA Adducts; D004317:Doxorubicin / Q000494:pharmacology*; D004338:Drug Combinations / Q000494:pharmacology; D006084:Graft Rejection / Q000187:drug effects*; D007166:Immunosuppressive Agents; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew
D018736:DNA Adducts; D004338:Drug Combinations; D007166:Immunosuppressive Agents; C031902:doxorubicin-DNA; D004317:Doxorubicin; D004247:DNA; D003404:Creatinine