A Potential Antidote for Both Azide and Cyanide Poisonings.

There do not appear to be any established therapeutics for treating azide poisoning at this time, and presently available antidotes to cyanide poisoning are far from ideal, being particularly impractical for use if multiple victims present. The cobalt (II/III) complex of the Schiff-base ligand -[14]-diene (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CoN[14]) is shown to act as an effective antidote to both azide and cyanide toxicity in mice. Groups of animals challenged with an LD dose of NaCN (100 µmol/kg i.

Oxidant-Dependent Sensitizing, Protective, and Mitigative Effects in X-Ray-Irradiated Pulmonary Endothelial Cells.

The primary response of proliferating bovine pulmonary artery endothelial cells (BPAECs) after X-ray irradiation [≤10 gray (Gy)] is shown to be transient cell-cycle arrest. Accompanying oxidant-linked functional changes within the mitochondria are readily measured, but increased autophagy is not. Radiation-induced apoptosis is negligible in this line-important because cells undergoing apoptosis release oxygen-derived species that can overwhelm/mask the radiation-associated species and their effects that we wish to investigate.

A Comparison of Potential Azide Antidotes in a Mouse Model.

Three cobalt-containing macrocyclic compounds previously shown to antagonize cyanide toxicity have been comparatively evaluated for the amelioration of sublethal azide toxicity in juvenile (7-8 weeks) Swiss-Webster mice. The lowest effective doses were determined for hydroxocobalamin, a cobalt porphyrin, and a cobalt-Schiff base macrocycle by giving the antidotes 5 min prior to the toxicant, 27 mg (415 μmol) /kg sodium azide. Both male and female mice were evaluated for their response to the toxicant as well as the antidotes, and no significant differences were noted once weight differences were taken into account.

A Cobalt Schiff-Base Complex as a Putative Therapeutic for Azide Poisoning.

There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.

Antidotal Action of Some Gold(I) Complexes toward Phosphine Toxicity.

Phosphine (PH) poisoning continues to be a serious problem worldwide, for which there is no antidote currently available. An invertebrate model for examining potential toxicants and their putative antidotes has been used to determine if a strategy of using Au(I) complexes as phosphine-scavenging compounds may be antidotally beneficial. When Galleria mellonella larvae (or wax worms) were subjected to phosphine exposures of 4300 (±700) ppm·min over a 20 min time span, they became immobile (paralyzed) for ∼35 min.

Assessing modulators of cytochrome c oxidase activity in Galleria mellonella larvae.

Caterpillars of the greater wax moth, Galleria mellonella, are shown to be a useful invertebrate organism for examining mitochondrial toxicants (inhibitors of electron transport) and testing putative antidotes. Administration of sodium azide, sodium cyanide, or sodium (hydro)sulfide by intra-haemocoel injection (through a proleg) results in a dose-dependent paralysed state in the larvae lasting from <1 to ~40 min. The duration of paralysis is easily monitored, because if turned onto their backs, the larvae right themselves onto their prolegs once they are able to move again.

A Comparison of the Cyanide-Scavenging Capabilities of Some Cobalt-Containing Complexes in Mice.

Four cobalt-containing macrocyclic compounds previously shown to ameliorate cyanide toxicity have been comparatively evaluated with an acute sublethal toxicity model in conscious (unanesthetized) adult male Swiss-Webster mice. All of the compounds (the cobalt-corrins cobalamin and cobinamide, a cobalt-porphyrin, plus a cobalt-Schiff base macrocycle) given 5 min prior to the toxicant dose significantly decreased the righting-recovery time of cyanide-intoxicated mice, but the doses required for maximal antidotal effect varied. Additionally, all of the compounds tested significantly reduced the righting-recovery time when administered at either 1 or 2 min after cyanide intoxication, but none of the compounds tested significantly reduced the righting-recovery time when delivered 5 min after the toxicant dose.

Sulfide Toxicity and Its Modulation by Nitric Oxide in Bovine Pulmonary Artery Endothelial Cells.

Bovine pulmonary artery endothelial cells (BPAEC) respond in a dose-dependent manner to millimolar (0-10) levels of sodium sulfide (NaHS). No measurable increase in caspase-3 activity and no change in the extent of autophagy (or mitophagy) were observed in BPAEC. However, lactate dehydrogenase levels increased in the BPAEC exposed NaHS, which indicated necrotic cell death.

Cyanide Scavenging by a Cobalt Schiff-Base Macrocycle: A Cost-Effective Alternative to Corrinoids.

The complex of cobalt(II) with the ligand 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaene (CoN4[11.

Antagonism of Acute Sulfide Poisoning in Mice by Nitrite Anion without Methemoglobinemia.

There are currently no FDA-approved antidotes for H2S/sulfide intoxication. Sodium nitrite, if given prophylactically to Swiss Webster mice, was shown to be highly protective against the acute toxic effects of sodium hydrosulfide (∼LD40 dose) with both agents administered by intraperitoneal injections. However, sodium nitrite administered after the toxicant dose did not detectably ameliorate sulfide toxicity in this fast-delivery, single-shot experimental paradigm.