Apr. 12, 1924 
Pharmacology of Gossypol 
195 
In the continued feeding experiments with rabbits evidence of the action of 
gossypol on the neuromuscular apparatus is found in the dribbling of the urine. 
This, however, was associated with motor paralysis, so that the point of attack 
might have been in the cord. 
EFFECT OF GOSSYPOL ON CIRCULATION 
Gossypol apparently also affects the neuromuscular apparatus of the heart, 
for frogs that have died from the slow absorption of gossypol injected in oil solu¬ 
tion into the ventral lymph sac show a peculiar spotted condition of the ventricle 
which presumably is associated with the fact that portions are in systole or rigor 
while other portions are fully stretched. In higher animals death comes from 
cardiac failure. Primarily the respiration is not at all or only slightly affected. 
Gossypol is a circulatory depressant. It produces a fall in blood pressure, 
usually immediately after it is injected. A recovery of pressure may occur 
gradually. Section of the vagi may bring it back to normal immediately, or, 
especially in rabbits, to above normal. For some time after injections of gossypol 
the heart shows skipped or weak beats. Once a two to one block was obtained 
which later disappeared spontaneously. Nevertheless, two cats receiving gossy¬ 
pol in continuous feeding experiments which died under observation gave no 
clinical evidence of irregularity of the heart rhythm. One cat, a good feeder, 
which received gossypol continuously and which died with edema of the lung, 
had decided shortness of breath and rapid pulse and* breathing before death. 
The enlarged heart is shown in Plate 2, a. Several other cats showed the same 
symptoms. 
EDEMA FROM GOSSYPOL 
Edema may follow gossypol injections as well as gossypol feeding. Marked 
edema of the ears of rabbits develops when gossypol solutions are injected into 
the ear veins, presumably owing to a slight leakage of the solution into the peri¬ 
vascular tissue. Edema also occurs around oil solutions of the gossypol in the 
subcutaneous tissue. Marked serous exudation follows in cats, rabbits, and 
rats when peanut oil solutions are injected intraperitoneally. In several cats 
which survived and subsequently were examined the ascites was intense and 
protracted. The injection of the oil free from gossypol does not ordinarily give 
rise to any visible serous exudate in the case of rats and only very little in the 
case of cats or rabbits. 
When gossypol is injected intravenously in alkaline solution, or intraperito¬ 
neally in oil solution, edema of the lungs occurs in rabbits, guinea pigs, cats, rats, 
and mice. This is more intense and appears sooner the larger the dose. The 
fatal edema is hemorrhagic and red exudation may appear at the nose. Edema 
of the lungs also occurs in cats in chronic intoxication from gossypol feeding. 
Some effusion into the serous cavities may be noted. Measurements were made 
of the limbs of paralyzed cats but no disproportion was evident. Upon recovery 
from paralysis there was possibly a slight decrease in the size of the limbs, per¬ 
haps connected with the disappearance of an edema. 
POST-MORTEM EXAMINATION 
Data on the toxicity of gossypol administered intravenously in fixed oil are 
given in Table II. The rabbits which died did so usually within one to two 
days, whereas the cats, except those given large doses, lingered for four to five 
days. The time of death of the rats varied. 
Examination by the Marchi method of the sciatic nerve from several paralyzed 
cats revealed degeneration. Dr. M. C. Winternitz, who also examined the 
experimental animals of Macy and Mendel (5), very kindly made histological 
88286—24f-8 
