Comparative study of the tissue distribution of equimolar repeated doses of hydroxocobalamin and cobalt chloride in the rats.

High dose of the cobalt atom is toxic for mammals. Hydroxocobalamin is considered safe due to the inclusion of the cobalt atom into the heminic moiety. The tissue distribution of cobalt following repeated doses of either hydroxocobalamin or cobalt chloride was studied in Wistar rats. In both cases, cobalt was administered in equimolar doses daily for an overall period of three weeks. Three groups were designed. In the hydroxocobalamin treated group, ten rats received hydroxocobalamin 17.5 mg by intraperitoneal route daily. In the cobalt-treated group, ten rats received cobalt chloride 3 mg i.p. daily. In the control group, six rats received a daily injection of 0.35 mL isotonic sodium chloride i.p. Cobalt concentrations were measured by Inductively Coupled Plasma Atomic Emission. Ours results showed that in rats having received either hydroxocobalamin or cobalt chloride, the tissue concentrations of cobalt were greater than those in the control group. The present study documented that in naive rats, the repeated administration of high doses of cobalt as hydroxocobalamin leads to tissue concentrations of the atom of cobalt significantly lower than those induced by equimolar doses of cobalt administered as cobalt chloride (p <0.05). We conclude that hydroxocobalamin reduced the tissue distribution of the cobalt atom in comparison with cobalt chloride.

Basic measures and systemic medical treatment of patients with toxic epidermal necrolysis.

BACKGROUND: With an incidence of 1.5-1.8/1 million inhabitants per year, toxic epidermal necrolysis is a rare but life threatening disease. It is almost always drug-induced and its lethality is pronounced with up to 50 %. Several therapeutic options are described in literature; however, there is still lack of a universally accepted and specific therapy of toxic epidermal necrolysis. METHODS: This survey considers 8 cases of toxic epidermal necrolysis diagnosed and treated in our clinic from 2003 to 2007. The epidermal sloughing was > 30 % of the body surface in each case. RESULTS: After immediately discontinuing the drug suspected of being responsible for toxic epidermal necrolysis, we treated with systemic corticosteroids in an initial dose of up to 1.5 mg/kg. Moreover, special emphasis was put on basic measures such as control of vital parameters. With this treatment we reached good results; none of the patients died. conclusions: Immediate beginning of therapy is essential for a successful treatment of toxic epidermal necrolysis. Besides systemic therapy with corticosteroids, certain basic measures such as isolation of patients at adequate room temperature to prevent hypothermia, strict control of circulation, temperature and laboratory parameters, daily smears of skin and mucous membranes and a diet rich in calories due to the catabolic metabolic status are very important for successful outcome.

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.

BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.

The antidote effect of thiosulphate and hydroxocobalamin in formation of nitroprusside intoxication of rabbits.

Sodium nitroprusside (SNP) and hydroxocobalamin (HC) - in molar ratios of 1:4, 1:5, and 1:8, respectively - were infused simultaneously during 4 h into two veins of separate ears of conscious rabbits. Controls received HC only. Sodium thiosulphate (ST) was infused with SNP at molar ratios of 1:4, 1:5, and 1:10. The observation period was 48 h. With the lowest dose of HC (1:4), SNP produced a severe metabolic acidosis; three of ten animals died during the infusion, an additional six within 24 h. When the 1:5 ratio was administered, the acidosis was less marked, but still three of seven animals succumbed within 24 h. The highest dose (1:8) prevented acidosis, however three of eight animals died. All doses of HC caused histological changes in the liver, the myocardium, and the kidney, independently if given alone or with SNP. In contrast to this, ST had a complete antidote effect, if administered in a 1:5 ratio; no acidosis was demonstrable and death did not occur. In neither dosage ST could prevent histological changes in the liver, but the kidney and the heart were not affected. In contrast to HC ST alone did not cause histological alterations. Consequently, ST is the preferable antidote and is superior to HC for preventing or treating intoxications with SNP.

Hydroxocobalamin therapy of cyanide intoxication in guinea pigs.

The efficacy of hydroxocobalamin (vitamin B12a) as a specific, nontoxic antidote in acute cyanide poisoning was tested. Guinea pigs receiving lethal intravenous NaCN injections were treated with either vitamin B12a or saline solution. There was a statistically significant antidotal effect of the vitamin. No toxic effect was observed with large doses of the vitamin.