Reduction by norepinephrine of the side effects induced by combined hepatic arterial administration of degradable strach microspheres and adriamycin in rats with a liver adenocarcinoma.
In previous studies we found degradable starch microspheres (DSM) to increase the antitumor effect of adriamycin injected by the hepatic artery in rats with a liver adenocarcinoma. Increased side effects also appeared, namely body weight loss and liver necroses. In the present paper, norepinephrine in four different protocols was added to the injection of adriamycin + DSM to decrease the drug flow to normal tissues. In two protocols norepinephrine decreased the body weight loss. There was also a non-significant decrease in liver necroses but also in antitumor effect. In these experiments we also observed that some rats given adriamycin + DSM got gastric necroses. This was not found when norepinephrine was added. Addition of propranolol to norepinephrine did not decrease side effects. Vasoactive drugs may therefore be of value to diminish adverse side effects of the combination cytostatic agent + DSM, probably decreasing overspill into normal tissues.
Jakobsson
B
B
Department of Pathology, Lund University, Sweden.
Teder
H
H
Roos
G
G
Stenram
U
U
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D008863:Microspheres; D009336:Necrosis; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013213:Starch / Q000008:administration & dosage*
D004317:Doxorubicin; D013213:Starch; D011433:Propranolol; D009638:Norepinephrine