The goal of the present investigation was to show that gossypol has the potential of ion interference capable of affecting the metabolic activation of the biologic system. Gossypol was administered orally at 20 mg/kg body weight (bw) for 8 weeks and the animals were fed a controlled diet. At the end of the experiment, liver supernatant was subjected to atomic absorption spectrometry. The characteristic ion interferences were examined for calcium, ferrous, sodium, magnesium, potassium and chloride ions. Glutathione level and lactate dehydrogenase activity were also monitored. The peak heights for calcium and ferrous ions were high and low respectively but the ion ratio for calcium is suggestive of a ligand-like substance that may be cumulative, thereby leading to biologic magnification (toxicity).

Oral administration to rats of chloroquine (5 mg/kg) three times per week for 8 weeks was investigated in two nutritionally compounded diets. It was observed that ferrous ion was preferentially retained in the presence of high (25%) protein diet even though all other ions, Ca2+, Mg2+ and K+ had varying uptake. The study shows no effect on the utilization of glucose and acid phosphatase. The difference in the level of lactate dehydrogenase (LDH) in both diets was not statistically significant. However, the level of cholesterol was significantly lower in both high and low protein diets when compared to control, suggesting that chloroquine biotransformation may interact with cholesterol metabolism in an unknown manner. The decrease in total cholesterol content corresponds to a similar decrease in malondialdehyde formation (lipid peroxidation). This result suggests that the biologic effects of chloroquine including its antimalarial action may be directly related to its lysosomotrophism.