Carbon disulfide. Just toxic or also bioregulatory and/or therapeutic?

The overview presented here has the goal of examining whether carbon disulfide (CS2) may play a role as an endogenously generated bioregulator and/or has therapeutic value. The neuro- and reproductive system toxicity of CS2 has been documented from its long-term use in the viscose rayon industry. CS2 is also used in the production of dithiocarbamates (DTCs), which are potent fungicides and pesticides, thus raising concern that CS2 may be an environmental toxin. However, DTCs also have recognized medicinal use in the treatment of heavy metal poisonings as well as having potency for reducing inflammation. Three known small molecule bioregulators (SMBs) nitric oxide, carbon monoxide, and hydrogen sulfide were initially viewed as environmental toxins. Yet each is now recognized as having intricate, though not fully elucidated, biological functions at concentration regimes far lower than the toxic doses. The literature also implies that the mammalian chemical biology of CS2 has broader implications from inflammatory states to the gut microbiome. On these bases, we suggest that the very nature of CS2 poisoning may be related to interrupting or overwhelming relevant regulatory or signaling process(es), much like other SMBs.

Protective effect of diethyldithiocarbamate and carbon disulfide against liver injury induced by various hepatotoxic agents.

Diethyldithiocarbamate (DTC) and carbon disulfide (CS2), at nearly equimolar oral dose levels, protected mice against liver damage induced by carbon tetrachloride, chloroform, bromotrichloromethane, thioacetamide, bromobenzene, furosemide, acetaminophen, dimethylnitrosamine and trichloroethylene, as evidenced by the suppression of elevations in plasma GPT activity and liver calcium content, and of histopathological alterations. Both agents also prolonged hexobarbital sleeping time and zoxazolamine paralysis time in mice. DTC and SC, alone, given orally, decreased microsomal metabolism of several substrates (aniline, p-nitroanisole, hexobarbital, zoxazolamine, aminopyrine and 3,4-benzopyrene), CC14-induced lipid peroxidation, and cytochrome P-450 content. The loss of microsomal drug-metabolizing enzyme activity was also observed in the experiments in vitro using liver slices and isolated microsomes. Since a characteristic common to such diverse hepatotoxins is that they require metabolic activation before exhibiting hepatotoxicity, the protective mechanisms of DTC and CS2 may involve their interference with the process of metabolic activation of these hepatotoxins. The protective action of DTC may be mediated almost entirely through CS2 when administered orally and at least partly with parenteral administration, since, in CCl4-induced liver injury, DTC was most effective when given orally, while the action of CS2 was less dependent on the route of administration. Thus CS2 and CS2-producing agents in vivo such as dithiocarbamate derivatives and disulfiram may modify toxicological and pharmacological effects of foreign compounds by inhibiting microsomal drug-metabolizing enzyme activity in the liver.

Activity of organophosphorus compounds against oral stages of gasterophilus intestinalis and Gasterophilus nasalis.

Controlled tests of the efficacy of bot-active compounds, dichlorvos, trichlorfon, trichlorfon butonate, and carbon disulfide on the larvae of Gasterophilus intestinalis and Gasterophilus nasalis during their migratory period in the tissue of the mouth of horses and ponies were completed on experimentally induced and naturally acquired infections. Against the experimental parasitisms in pony foals, the resin-pellet formulation of dichlorvos given on the feed at the dose level of 37 mg/kg, 2 formulations of trichlorfon given by stomach tube at the dose level of 40 mg/kg, another of trichlorfon given on the feed, and trichlorfon butonate given intragastrically at the dose level of 43 mg/kg were 100% efficacious. Against naturally acquired parasitisms in horses, a broad-spectrum gel formulation of dichlorvos given intraorally at the dose level of 36 mg/kg was quite efficacious, whereas liquid carbon disulfide given by stomach tube at the dose level of 2.4 ml/45.45 kg was ineffective.