Metabolism and Excretion of Dimethyl Sulfoxide in Cows and Calves After Topical and Parenteral Application

Abstract

The therapeutic success experienced with dimethyl sulfoxide (DMSO) in man, horses, and dogs raised questions as to whether this drug could feasibly be used for the treatment of disease conditions in the food-producing bovine and porcine species. Prerequisites for the therapeutic employment of the drug in cattle or swine are knowledge of its metabolism and excretion patterns in these species, and of the possibilities that exist for tissue residues of DMSO or its more important metabolites.The studies reported here deal with DMSO metabolism and excretion in cattle. They show that the bovine species metabolizes and excretes DMSO and its two main metabolites, DMS and DMSO?, fast and effectively. This is not surprising, since DMSO, has long been known to occur in cattle blood' and adrenal glands,? and DMS and DMSO, are components of the cow's Materials and MethodsThree male dairy calves, 2 to 4 weeks of age, that weighed 50 to 65 kg (Trials 1 to 3), and two three-year old dairy cows (Holstein) that produced 10 kg milk (Trial 4) and 16 kg milk (Trial 5) daily, were used. The calves were housed in metabolic cages at room temperature, and were fed a commercial milk-replacer diet. Urine and feces were collected separately. The cows were kept in stalls, and received hay ad lib. and 4 kg concentrate daily. Cows were milked by hand, and each quarter was milked separately. Feces were not collected from cows, but urine was collected thus: indwelling catheters were inserted into the bladder and emptied into plastic containers.Routes of application of [14C]DMS0, the amounts of DMSO, and the specific activities employed are given in TABLES 1 and 2.Determination of I4C-Activities in Urine Samples. Three ml fresh urine were combined with 10 ml scintillation liquid (4 g 2,5-diphenyloxazole [PPO] and 100 mg dimethyl-l,4-bis-2-[5-phenyloxazolyl]-benzene [dimethyl-POPOP] in 1 liter toluol) and 10 ml Triton@ X-100, and were placed in scintillation tubes. The well-shaken tubes were placed in a liquid scintillation spectrometer and were measured three times. An internal standard ([14C]toluol; liquid scintillation spectrometer model 3 14Ex, Packard Instruments) or external standard (liquid scintillation spectrometer, model 3375, Packard Instruments) were used to make quench 139

Metabolic Fingerprint of Dimethyl Sulfone (DMSO2) in Microbial–Mammalian Co-metabolism

“…For example, in 1975, Tiews et al showed that oral administration of 50 g D,L-methionine increased DMSO 2 in calf urine. 163 D,L-methionine supplementation in lactating cows yields more DMS in milk than feeding sulfur or hay alone. 164 Clark and Salsbury showed the oral administration of 60 or 80 g of D,L-methionine resulted in the appearance of DMS in milk.…”

“…Interestingly, DMSO 2 levels increases considerably after a large flux of methionine administration. For example, in 1975, Tiews et al showed that oral administration of 50 g d , l -methionine increased DMSO 2 in calf urine .…”

Dimethyl Sulphoxide Reduction by Micro-organisms

“…Certain pesticides are highly toxic to mammals when in the sulphoxide form, and microbial reduction may serve to detoxify them (Alexander, 1974). DMSO reduction to DMS has been shown in the cat (Distefano & Borgstedt, 1964), in the cow and other animals (Tiews et al, 1975) and in plants (Smale, Lasater & Hunter, 1975). Ando et al (1957) surveyed members of the Enterobacteriaceae and found that while all strains of Escherichia coli tested reduced DMSO, no strains of Shigella and only one out of 40 strains of Salmonella reduced it; they suggested that this reaction might be of diagnostic value.…”

Emerging Chemical Diversity and Potential Applications of Enzymes in the DMSO Reductase Superfamily

“…The conversion of DMSO to dimethyl sulfide is ubiquitous in many environments (23)(24)(25) and is especially relevant under anaerobic conditions in which DMSO is employed as a terminal electron acceptor (26) (Figure 2a). Efforts to identify and characterize the enzyme responsible for this transformation led to the structural elucidation of the unique bis-MGD cofactor (27).…”