Presence Of BSO Research Articles

Protection by dimethylsulfoxide against acetaminophen-induced hepatic, but not respiratory toxicity in the mouse

Dimethylsulfoxide (DMSO) is used as a vehicle for the administration of compounds that are difficult to solubilize. Acetaminophen (AP), typically administered ip in hot basic saline, dissolves readily in DMSO. However, since DMSO acts as a free radical scavenger in vitro, and since AP toxicity may be mediated through oxidative stress, we examined the possibility that DMSO might protect against AP toxicity. Survival of mice 96 hr after AP (900 mg/kg ip) was increased from 10 to 60% by concomitant DMSO administration (4 g/kg sc). Adult female Swiss inbred mice given AP (800 mg/kg ip in hot basic saline) exhibited severe centrilobular hepatic necrosis, pulmonary nonciliated bronchiolar epithelial (Clara cell) necrosis and nasal epithelial necrosis. DMSO (8 g/kg 50% in saline) protected against AP hepatotoxicity, whether administered prophylactically (14.5 and 2.5 hr before AP), concomitantly with AP, or antidotally (30 or 60 min post-AP). No treatment protected against pulmonary Clara cell damage. Nor did pretreatment with DMSO protect against AP-induced necrosis of nasal epithelium. Other treatment regimes were not evaluated for their effect on nasal epithelial toxicity. Since DMSO protection is tissue specific, it does not appear to be mediated by a nonspecific mechanism, such as scavenging of free radicals. Six hours after AP, glutathione (GSH) levels had dropped significantly in liver, but not in lung. AP-induced loss of hepatic GSH was slowed by DMSO even in the presence of BSO, an inhibitor of GSH synthesis. These findings are consistent with decreased utilization of GSH, due to decreased bioactivation of AP or decreased turnover of GSH.

Increased antineoplastic activity of combined hyperthermic and bleomycin treatments in an adenocarcinoma after glutathione depletionin vivo

We have earlier shown that glutathione depletion, achieved by BSO administration, only marginally increases the antineoplastic activity of hyperthermic or bleomycin treatments in C3H mammary adenocarcinoma, grown subcutaneously in the hind paw of CBA mice. In this study we evaluated the role of glutathione depletion on the antineoplastic activity of combined hyperthermic and bleomycin treatments on the same tumour model system. The activity was recorded by determination of tumour volumes 12 days after treatment and by tumour regression frequencies. When hyperthermic and bleomycin treatments were combined, their respective effects on the 12-day volume values were additive, irrespective of treatment sequence and presence of BSO. However, BSO increased significantly the tumour regression frequencies accomplished by combined hyperthermic and bleomycin treatments, particularly of hyperthermic treatments given together with or 24 h after bleomycin. It is not possible to conclude, at present, whether this effect is caused by low glutathione levels.