Enhancement of adriamycin toxicity by carboxymethylcellulose in mice

Carboxymethylcellulose (CMC) (1% in 0.9% NaCl, 0.2 ml/10 g ip) a common suspending agent, enhanced adriamycin (ADR) (15 mg/kg ip) toxicity when administered to mice 5 hr before the antibiotic. Compared with ADR alone, this combination treatment produced, after 7 days, an increase in lethality from 15 to 80%. The pathologic analysis of hearts, livers, kidneys, and small bowels was performed, revealing an increase in the incidence and severity of hepatic damage in mice receiving ADR + CMC. Furthermore, reduced glutathione (GSH) was measured in livers of all mice; the animals treated with CMC and ADR + CMC showed a significant (p less than 0.01) reduction of hepatic GSH in comparison with controls and ADR-alone-treated animals. These data further confirm a crucial protective role for GSH in ADR toxicity and prove that CMC exerts an important biochemical effect on hepatic GSH.