Toxicokinetics of cotyledoside following intravenous administration to sheep

Abstract

INTRODUCTIONKrimpsiekte, a chronic form of cardiac glycoside poisoning, manifests as a paretic syndrome and occurs predominantly in small stock 5,6 . The disease develops following ingestion of certain members of the Crassulaceae (Cotyledon, Tylecodon and Kalanchoe species). Krimpsiekte is generally believed to be caused by cumulative bufadienolides, with unique neurotoxic properties, encountered in these genera 5,7 . Naudé and Schultz 8 coined the term 'cumulative bufadienolides' following the successful demonstration of a cumulative effect with cotyledoside isolated from Tylecodon wallichii. These authors determined a subcutaneous LD50 of 0.116 mg/kg cotyledoside in guinea pigs and then injected others subcutaneously with 25 % and 50 % of the subcutaneous LD50 per day until they died. No clinical signs appeared before the LD50 was reached and marked nervous signs occurred when 5 × 25 % or 3 × 50 % the LD50 were administered 8 .Repeated intravenous cotyledoside administration at 0.01-0.015 mg/kg body mass to sheep induced krimpsiekte,

Evaluation of a commercially available molybdate formulation and zinc oxide boluses in preventing hepatic copper accumulation and thus enzootic icterus in sheep

“…There are conflicting reports in the literature regarding the ability of tetrathiomolybdate to increase copper excretion in the urine 3,9,14 , but in this experiment the molybdate therapy did not significantly increase cupruresis in relation to the other groups (Fig. 4).…”

“…It is surmised that the TCA-insoluble copper is not taken up by red blood cells and this inability to penetrate erythrocytes is the reason why haemolysis is not precipitated and increased urinary copper excretion occurs 9 . Other researchers reported that tetrathiomolybdate treatment had no effect on the rate and amount of copper excreted in the urine 3,14 .…”

Teores séricos e hepáticos de cobre, ferro, molibdênio e zinco em ovinos e caprinos no estado de Pernambuco

“…Quanto aos valores séricos, estes são inferiores aos encontrados por diferentes autores. Van Ryssen & Stielau (1981) encontraram valores de 0,63 ±0,21μmol/L, quando avaliaram o efeito de diferentes ní-veis de Mo dietético no metabolismo do Cu e Mo em ovinos alimentados com elevados teores de Cu e S. Botha et al (1995), encontraram 0,52 ±0,42μmol/L, estudando a farmacocinética do tetratiomolibdato em ovinos e Antonelli (2007), encontrou teores séricos de 0,8±0,19μmol/L, quando estudou o efeito do uso de sal mineral rico em Mo na intoxicação cúprica cumulativa. Apenas Pott et al (1999), avaliando o efeito de dietas com elevado teor de Mo no metabolismo do Mo e Cu em ovinos, encontraram valor médio de Mo hepático (0,10μmol/L) inferior aos encontrados neste estudo.…”

Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry

“…An elimination half-life (T1/2 beta) of 396.8 min, steady state volume of distribution (Vdss) of 0.8 e kg-1 and total body clearance (C1B) of 1.53 ml kg-1 min-1 were observed using non-linear compartmental analysis. A significant (p < or = 0.05) increase in molybdenum excretion in the faeces occurred at 24 and 48 h following TM administration [61]. …”