Molybdenum in Biology - An Essential Trace Element

Effect of molybdenum on other trace elements-copper

Molybdenum affects the concentrations of other trace elements in the blood and tissues but, except for copper, the interrelationships have not been studied in detail. The interest in the molybdenum-copper relationship arises in connection with the teart condition of sheep and cattle. In the sheep feeding 3 mg Mo/kg live weight as sodium molybdate decreased iron in the blood (by 15%) and increased zinc (by 24%) [Kholod, 1969]. An excess of either copper or molybdenum forms an undissociated Cu-Mo-S complex thereby creating a deficiency of the metal in marginal supply. In the United States dietary excess of copper is common and molybdenum intake may not be optimal. The consequence is a conditioned deficiency of molybdenum which may contribute to abnormalities of iron metabolism and utilisation. Certain forms of anaemia which do not respond to iron therapy, respond to molybdate [Seelig, 1972, 1973].

Kholod, V. M., Uch. Zap. Vitebsk . Vet. Inst., 1969, 21 , 64.
Seelig, H. S., Amer. J. Clin. Nutr., 1972, 25 , 1022; 1973, 26 , 657.

Because of the copper-molybdenum interrelationship and the relationship to sulfate intake, any evaluation of the possible hazard from elevated molybdenum intake in the diet must be related to the concurrent intake of sulfate and copper. In non-ruminants excessive intakes of sulfate will be a key factor in causing copper antagonism [Arthur, 1965]. An evaluation of the quantitative aspects of the copper-molybdenum-sulfate interrelationships required for the assessment of molybdenum dietary risk has been considered [Clarke and Clarke, 1975].

Clarke, E. G. C. and Clarke M. L., Molybdenum in: Veterinary Toxicology, Wilkins & Wilkins, Baltimore, Maryland, 1975, 86.

Molybdenum (and copper) influence the internal transport and release of iron [Seelig, 1972, 1973]. Molybdenum in xanthine oxidase participates in reduction of cellular iron(III) to iron(II).

Seelig, H. S., Amer. J. Clin. Nutr., 1972, 25 , 1022; 1973, 26 , 657.

High dietary levels of molybdenum produce a conditioned copper deficiency by depleting copper storage in the liver. The antagonism between molybdenum and copper is most pronounced in ruminant animals and gives rise to molybdenosis. For example, liver copper decreased and milk copper concentrations increased in dairy cows on feed containing sodium molybdate (53-300 ppm).

Huber, J. T., Price, N. O. and Engel, R. W., J. Animal Sci., 1971, 32 , 364.

Sulfate limits molybdenum retention both by reducing its gastrointestinal absorption and by increasing its urinary and faecal excretion. The transport of molybdenum across tissue membrane is prevented by excess of sulfate ions [Venugopal and Luckey,1978]. Sulfate may also displace molybdate in the body. So copper, sulfate, and copper sulfate have been used to treat conditions due to excessive molybdenum [Arrington and Davis, 1953].

Venugopal, B. and Luckey, T. D., Metal Toxicity in Mammals , 1978, Vol. 2 , Chemical Toxicity of Metals and Metalloids, Plenum Press, New York .
Arrington, L. R. and Davis, G. K., J. Nutr. , 1953, 99 , 295.

Molybdenum toxicity occurs in cattle and, to a less extent, in sheep on pastures with relatively high molybdenum contents (20-100 ppm compared with 3-5 ppm on "normal" pastures) [Underwood, 1962; Kolomiitseva et al., 1968; Schroeder et al., 1970; Lukashev, 1973; Huisingh et al., 1973; Dick, 1969; Grace, 1969; Clawson et al., 1972; Mareilese et al., 1970].100 ppm Mo in feed is definitely toxic to cattle. Levels of 25 to 50 ppm in feeds have shown mixed results and sometimes no effects. Effects atributed to feeds containing less than 25 ppm Mo have often been associated with very low Cu levels and poorly avilable Cu [Ward, 1994].

Underwood, E. J., in Trace Elements in Human and Animal Nutrition, Academic Press, London , 2nd Ed., 1962, pp. 100-122.
Schroeder, H. A., Balassa, J. J.and Tipton, I. H., J. Chronic Diseases, 1970, 23 , 481.
Ward, G.M., Molybdenum requirements, toxicity and nutritional limits for man and animals, Studies in Inorganic Chemistry, 1994, 19 , 452 - 476.
Lukashev, A. A., Grig. Tr. Prof. Zabol., 1973, 12 , 13.
Kolomiitseva, M. G., Polonskaya, M. N.and Osipov, G. K., Mikroelem. Sel. Khoz. Med., 1968, 4 , 183
Huisingh, J., Gomez, G. G. and Matrone, G., Fed. Proc., Fed. Amer. Soc. Exp. Biol., 1973, 32, 1 921.
Dick, A. T., Australian Vet. J., 1952, 28, 30; 1953, 29, 18, 233; 1954, 30, 196.
Dick, A. T., in Inorganic Nitrogen Metabolism, ed. McElroy, W. D. and Glass, B., John Hopkins Press, Baltimore, 1956, p. 445.
Dick, A. T., Outlook Agr., 1969, 6, 14
Grace, N. D., Proc. N. Z. Grassl. Ass. , 1969, 31 , 65.
Clawson, W. J., Lesperance, A. L., Bohman, V. R. and Layhee, D. C., J. Anim. Sci., 1972, 34 , 516.
Mareilese, N. A., Ammerman, C. B., Valsecchi, R. M., Dunavant, B. G. and Davis, G. K., J. Nutr. , 1969, 99 , 177.

The excess of molybdenum causes a condition known as "teart" which is characterised by scouring (diarrhoea), rapid loss of weight and condition, the development of harsh, discoloured coats, and ultimately death. That a similar condition occurred in cattle on copper-deficient pastures led to the realisation that molybdenum is a copper antagonist, i.e. interferes with the uptake or utilisation of copper. Hence, molybdenum poisoning also known as, "Molybdenosis", "Teart Syndrome" or "Peatscours", is a secondary copper deficiency manifested by diarrhoea, anorexia, depigmentation of the hair or wool, neurological disturbances and premature death [Wennig and Kirsch, 1988; Friberg and Lener, 1986]. The condition can be treated by giving affected animals extra copper in their feed or by injecting copper glycinate.

Webb, J. S., Geol. Soc. Amer., Mem., 1971, 123 , 31.
Wennig, R., and Kirsch, N., in: Handbook on Toxicity of Inorganic Compounds , Seiler, H. G., Sigel, H., and Sigel, E. (eds.),1988 , 437. Marcel Dekker , New York.

Because of its importance in agriculture and relevance to understanding the metabolism of molybdenum and copper, the mechanism of the molybdenum-copper antagonism has been extensively studied in cattle, sheep, and experimental animals. In the causation of teart molybdenum and sulfate are both required: neither is effective alone. The effect of molybdenum plus sulfate is to increase accumulation of copper in the kidney and increase excretion of copper by way of urine [Dick, 1969; Mareilese et al., 1970]. Various mechanisms have been proposed. The antagonism of molybdenum and copper is considered to be due to the formation of copper sulfide [Kazakov, 1970]. An important finding is that molybdenum plus sulfate reduce formation of ceruloplasmin (a copper binding protein in the blood) and increase the inorganic plasma copper or copper loosely bound to albumin. Molybdenum causes an impairment of copper uptake by liver cells, and thus disturbs the synthesis of copper-containing proteins, including ceruloplasmin [Mareilese et al., 1969]. Molybdenum depresses liver sulfide oxidase activity [Halverson et al., 1960]. The resulting sulfide accumulation leads to the formation of highly insoluble cupric sulfide and the subsequent appearance of symptoms of copper deficiency. However, copper prevents the accumulation of molybdenum in the liver by antagonising the absorption of molybdenum. The point of general interest which emerges from these investigations is the close relationship between the metabolism of molybdenum, copper, and sulfate [Miller and Engel, 1960]. The effect of molybdenum on copper metabolism is greatest in species with a relatively high copper requirement. So cattle and sheep are more susceptible than rabbits, horses, and human beings to molybdenosis.

Dick, A. T., Outlook Agr., 1969, 6, 14
Mareilese, N. A., Ammerman, C. B., Valsecchi, R. M.and Dunavant, B. G., J. Nutr., 1970, 100, 1399.
Kazakov A. M., Gig. Sanit., 1970, 35 ,19.
Mareilese, N. A., Ammerman, C. B., Valsecchi, R. M., Dunavant, B. G. and Davis, G. K., J. Nutr., 1969, 99, 177.
Halverson, A. W., Phifer, J. H. and Monty, K. J., J. Nutr., 1960, 71 , 95.
Miller, R. F., Price, N. O. and Engel, R. W., J. Nutr., 1956, 60 , 539.

Copper deficiency, or molybdenosis in cattle, sheep and horses, occurred after heavy pollution of a pasture with fly ash. Molybdenum intoxication, seldom seen in non-ruminants, was blamed on the high bioavailability of molybdenum in fly ash. The fly ash was used in road construction. It blew over and contaminated pasture and water. Cows, sheep and horses exhibited Mo intoxication leading to death. The fly ash pH was ca 10 giving high bioavailabilityof Mo. Copper was low in exposed animals (ca 4 mg/kg wet cf control ca 18) but Mo was normal (ca 1.4) possibly because of the ‘short’ biological half life of Mo (24 h). See Table.

Ladefoged, O., Sturup, S., Copper Deficiency In Cattle, Sheep And Horses Caused By Excess Molybdenum From Fly-Ash - A Case-Report, Veterinary And Human Toxicology , 1995, 37 , 63-65.

The effects of increased dietary concentrations of molybdenum and sulfur on the accumulation and tissue concentrations of cadmium in sheep were determined and compared with effects on copper. A basal diet containing (per kg dry weight) 0 . 016mg Cd, 0 . 45 mg Mo, 3 . 4 mg Cu, and 1 . 9 g S. was fed to four dietary treatment groups: control (basal diet plus 4 mg Cd/kg), +Mo (control diet plus 15 mg Mo/kg), +S(control diet plus 4 g S/kg), +Mo+S (control diet+15 mg Mo+4 gS/kg).The treatment period lasted 80 days, Sulfur alone reduced the accumulation of Cd in liver, kidney, and muscle by 60% Molybdenum alone reduced Cd accumulation by 40% in liver and muscle and 30% in kidney . When provided together (+Mo+S), the effect was equivalent to feeding with Mo alone, showing that Mo blocked the effect of S. For Cu in blood and tissues, the effects of Mo and S treatment were consistent with the thiomolybdate hypothesis, and were quite different from those seen for Cd.. The results show that increased dietary levels of Mo and S reduce the accumulation of Cd in tissues, and the mechanisms of action differ from those involving Cu [].

Smith, G.M., White, C.L., Molybdenum-sulfur-cadmium interaction in sheep, Australian Journal Of Agricultural Research , 1997, 48, 147-154.

Molybdenosis has been reported in Swedish moose.

Frank, A, 'Mysterious' moose disease in Sweden . Similarities to copper deficiency and/or molybdenosis in cattle and sheep, Biochemical background of clinical signs and organ lesions, Science Of The Total Environment , 1998, 209 , 17-26.


Molybdenosis risk to cattle consuming corn stover (winter food for cattle) produced on biosolids-amended land is small. Stover Mo concentrations were always low and stover Cu to Mo ratios exceeded 2:1, which avoids molybdenosis problems even at very high biosolids loads and soil Mo loads estimated to be near 18 kg Mo/ha. Data from long-term (continuous corn) plots in Fulton County , IL confirm expected low Mo accumulation by corn stover. Data from plots in Minnesota also suggested essentially no correlations between stover Mo and soil Mo loads for continuous corn, However, greater Mo accumulation in corn grown following soybean [Glycine mar (L.) Merr.] suggests the possibility of enhanced Mo bioavailability to corn in corn-soybean rotations.

O'Connor, G.A., Granato, T. C., and Dowdy, R. H., Bioavailability of biosolids molybdenum to corn, Journal of Environmental Quality, 2001, 30 , 140-146.


Thiomolybdates formed in the rumen are known to be involved in copper deficiency in ruminants. However, which particular thiomolybdates are formed has been an issue of contention. The relative proportions of the different thiomolybdates, formed under conditions simulating those within the rumen fluid of ruminants prone to copper deficiency, were measured using UV/visible spectroscopy. Pure synthesized thiomolybdates have also been used to study spectrophotometrically the interactions between the thiomolybdates and copper( II) in the presence and absence of some inorganic ligands, low molecular mass complexing agents and bovine serum albumin in aqueous solutions.

Quagraine, E.K. and Reid, R. S., UV/visible spectrophotometric studies of the interactions of thiomolybdates, copper(II) and other ligands, Journal of Inorganic Biochemistry, 2001, 85, 53-60

In human beings the absorption, tissue distribution, and excretion patterns of molybdenum are similar to those in other species described above. High dietary levels of molybdenum produces a conditioned copper deficiency in humans. Increased copper excretion and elevated levels of plasma copper were found in volunteers ingesting 1.54 mg of molybdenum daily [Deosthale and Gopalan, 1974]. Tungsten is antagonistic to molybdenum. It interferes with absorption and increases urinary excretion of molybdenum. The activities of molybdenum-dependent enzymes are inhibited in neonates when pregnant animals are fed tungsten. Tungsten is believed to replace molybdate in the molybdate-dependent enzymes [De Renzo, 1962]. As a result, sulfite oxidase and xanthine oxidase activities are reduced.

Deosthale, Y. G. and Gopalan, C., Br. J. Nutr., 1974, 31 , 351.
De Renzo, E. C., Molybdenum in Mineral metabolism: An Advanced Treatise , (eds) Comar, C. L. and Bronner, F., 1962, U Part B, 483. Academic Press, New York .
In parenteral micronutrition a Mo uptake of >0.5 mg/day can cause significant urinary copper losses .
Leung, F.Y., Trace-Elements In Parenteral Micronutrition, Clinical Biochemistry ,1995, 28, 561-566.

Using plasma copper levels alone to diagnose a molybdenum toxic condition is flawed.. Thiomolybdates are absorbed into the ruminant body and have toxic effects (molybdenum toxicity) on critical copper metallo-enzymes. The effects are impaired fertility and production. Prevention of molybdenum toxicity is achieved by reducing the iron intake of the animal and by supplementation with copper that is sacrificial in the rumen and not primarily supplied for absorption. A correct diagnosis will allow appropriate supplementation to be undertaken

Telfer, S.B., Kendall, N. R., Illingworth, D. V., and Mackenzie, A. M., Molybdenum toxicity in cattle: an underestimated problem, Cattle Practice, 2004, 12, 259-263.


Suttle, N. F., Relationships between the concentrations of trichloroacetic acid-soluble copper and caeruloplasmin in the serum of cattle from areas with different soil concentrations of molybdenum, Veterinary Record, 2008, 162, 237-240.

Molybdenosis: copper deficiency caused by high sulfur in forage

An ailment of Przewalski's gazelles in the Hudong area of the Qinghai Lake area in China was caused by secondary copper deficiency, mainly due to high sulfur content in forage. The ailment was characterized by pica, emaciation, dyskinesia, loss of appetite, and anemia. Concentrations of copper in soil and forage from affected and unaffected areas were similar and within the normal range, but concentrations of sulfur in soil and forage were higher (P < 0.01) in affected than in unaffected areas. Concentrations of copper in blood, hair, and liver from the affected Przewalski's gazelles were lower (P < 0.01) than those in healthy animals. Affected Przewalski's gazelles showed a hypochromic microcytic anemia and a low level of ceruloplasmin. Oral administration of copper sulphate (CuSO­4) prevented and cured the disease.

Zhou, L. Y., Long, R. J., Pu, X. Y., Qi, J., and Zhang, W. W., Studies of a naturally occurring sulfur-induced copper deficiency in Przewalski's gazelles, Canadian Veterinary Journal-Revue Veterinaire Canadienne, 2009, 50, 1269-1272.


Copper deficiency induced by molybdenum and iron metabolism in beef cattle

The impact of a severe, long-term Cu deficiency on Fe metabolism in beef cattle was studied over 493 days. Twenty-one Angus calves were born to cows receiving one of the following treatments

(1) adequate Cu (+Cu),

(2) Cu deficiency (-Cu) induced by the addition of 2 mg of Mo/kg of DM

(3) Cu deficient plus high Mn (-Cu+Mn).

After weaning, calves remained on the same treatment as their dam through growing (basal diet analyzed 7 mg of Cu/kg of DM) and finishing (analyzed 4 mg of Cu/kg of DM) phases.

Plasma Fe concentrations were positively correlated (P < 0.01; r = 0.49) with plasma Cu concentrations.

Liver Fe concentrations were greater (P = 0.05) in -Cu vs +Cu calves and further increased (P = 0.07) in -Cu+Mn vs -Cu calves.

There was a negative relationship (P < 0.01; r = -0.31) between liver Cu and Fe concentrations. This relationship may be explained by less (P < 0.01) plasma ceruloplasmin activity in -Cu than +Cu calves.

Relative expression of hepatic hepcidin, as determined by real-time reverse transcription-PCR, was significantly downregulated (> 1.5 fold) in -Cu compared with +Cu calves (P = 0.03), and expression of hepatic ferroportin tended (P = 0.09) to be downregulated in -Cu vs +Cu.

In the duodenum, ferritin tended to be upregulated in -Cu vs +Cu calves (P < 0.06).

No significant change (P > 0.2) due to Cu-deficiency was detected at the transcriptional level for either isoform of divalent metal transporter 1 (DMT1 mRNA with or without an iron responsive element; dmt1IRE and dmt1-nonIRE in liver or intestine.

Duodenal expression of hephaestin and ferroportin protein was not affected by dietary treatment (P > 0.20).

Duodenal expression of DMT1 protein was less (P = 0.04) in -Cu+Mn steers vs -Cu steers.

In summary, Cu deficiency alone did affect hepatic gene expression of hepcidin and ferroportin, but did not affect duodenal expression of proteins important in Fe metabolism. However, the addition of 500 mg of Mn/kg of DM to a diet low in Cu reduced duodenal expression of the Fe import protein DMT1

Hansen, S. L., Trakooljul, N., Liu, H. C. S., Hicks, J. A., Ashwell, M. S., and Spears, J. W., Proteins involved in iron metabolism in beef cattle are affected by copper deficiency in combination with high dietary manganese, but not by copper deficiency alone, Journal of Animal Science, 2010, 88, 275-283.

Molybdenum + sulfur effective in reducing retention and liver accumulation of dietary copper in sheep

Twelve male 8-month-old lambs were used in a 6-month feeding experiment to determine how dietary molybdenum, molybdenum + sulfur and zinc supplements affected the body retention and tissue accumulation of dietary copper, zinc and iron.

In comparison with the control, each dietary supplement decreased the copper concentration in the liver, but only the molybdenum + sulfur supplement decreased it to a safe range of below 350 mu g/g dry matter.

This was accompanied by the body retention of dietary copper for the control and dietary treatments:

control 24.6%,

Molybdenum 6.7%,

Molybdenum + Sulfur 2.5% and

Zinc 6.5%.

The blood plasma concentration of copper was decreased by the zinc supplement, but was not affected by other supplements.

Only molybdenum + sulfur appeared to be effective in reducing the retention and liver accumulation of the dietary copper to prevent chronic copper toxicity in sheep fed PKC-based diets

Al Kirshi, R. A., Alimon, A. R., and Ivan, M., Effects of dietary molybdenum, sulfur and zinc on the excretion and tissue accumulation of trace elements in sheep fed palm kernel cake-based diets, Animal, 2011, 5, 1539-1545.

Copper and molybdenum had no effect on reproductive performance in beef cows

Serum concentrations of copper and molybdenum were measured at the end of the summer grazing season in an observational field study of 783 breeding females from 66 cow-calf herds located in western Canada.

The mean copper concentration was 0.82 ppm (sulfur, 0.30 ppm) and the mean molybdenum concentration was 0.056 ppm (sulfur, 0.055 ppm).

Serum copper concentration differed across ecoregions. Serum molybdenum concentrations varied by ecoregion, soil type, soil color, and total precipitation during the growing season.

Copper and molybdenum serum concentrations at the end of the grazing season were not associated with reproductive outcomes.

Van de Weyer, Leanne M. and Waldner, Cheryl L., Geographic determinants of copper and molybdenum concentrations in serum at the end of the grazing season and associations with reproductive performance in beef cows from western Canada, Canadian Journal of Animal Science, 2011, 91, 423-431.

Urinary copper and zinc excretion in cattle require both sulfur and molybdenum

The effects of low and high levels of dietary copper, molybdenum (1.10 mg/kg DM) and sulfur on urinary copper and zinc excretion in cattle (four Simmental and four Angus heifers) were studied.

Urinary copper excretion was greatest with the high copper + high molybdenum + high sulfur diet.

Urinary zinc excretion increased with high sulfur but not with high sulfur in combination with high molybdenum and/or high copper.

Urinary copper excretion in sheep increased only when sulfur (1.1 g/day) was added to the basal diet (5.5 mg copper, 0.7 mg molybdenum) and not with increasing levels of molybdenum alone (5 to 25 mg/day).

The findings that dietary molybdenum and sulfur significantly increase copper excretion through the biliary and urinary routes are in agreement with the reported beneficial effects of molybdenum and sulfur in the treatment of copper-toxicity in sheep.

Observations for the combined effects of molybdenum and sulfur, but not

either on its own, are supported by other studies. For example, biliary

copper excretion in sheep was much greater with intravenous thiomolybdate

than with intravenous molybdenum.

It is the thiomolybdate formation that occurs when cattle are fed on high

molybdenum and sulfur diets and the copper chelation by thiomolybdate that is responsible for the increased concentration and excretion of urinary copper (and increased kidney copper concentration), with some of the excess plasma

copper filtered by the glomerulus reabsorbed by the kidney tubules.

In cattle fed a high copper + high molybdenum + high sulfur diet, it was the combined effect of high molybdenum and high sulfur that increased copper excretion through both routes, whereby significantly more copper was excreted through bile (0.81 mg/6 h) than through urine (0.29 mg).

Zinc excretion in bile (1.50 mg/6 h) and in urine (0.26 mg) was less influenced by the combination of high copper + high molybdenum + high sulfur in the diet. High sulfur alone contributed to significantly higher urinary zinc excretion than any other combination of dietary copper, molybdenum or sulfur.

[References in full text.]

Gooneratne, S. R., Laarveld, B., Pathirana, K. K., and Christensen, D. A., Effects of dietary Copper, Molybdenum and SULFUR on urinary Copper and Zinc excretion in Simmental and Angus cattle, Research in veterinary science, 2011, 91, e116-e120.

Copper deficiency in baboons due to zinc not molybdenum

In immature wild savannah baboons (Papio cynocephalus) symptoms of copper deficiency and a disorder referred to as white monkey syndrome (WMS) in laboratory primates were observed. Visible symptoms exhibited by WMS infants included whitening of the animal's fur and/or impaired mobility characterized by an apparent "stiffening'' of the hindlimbs

Three hypotheses were tested: that (1) copper deficiency may have been induced by zinc toxicity, (2) it may have been induced by molybdenum toxicity, and (3) cumulative rainfall during the perinatal period and particularly during gestation is an ecological factor distinguishing infants afflicted with WMS from non-WMS infants.

WMS males had a significantly lower survivorship probability than non-WMS males.

Zinc/copper ratios assessed from hair samples of adult female baboons were higher in females who had produced at least one WMS offspring relative to females who had not had a WMS offspring: low copper levels induced by elevated zinc intake in some individuals.

No significant differences of molybdenum/copper ratios were observed.

Markham, A. Catherine, Gesquiere, Laurence R., Bellenger, Jean Philippe, Alberts, Susan C., and Altmann, Jeanne, White Monkey Syndrome and Presumptive Copper Deficiency in Wild Savannah Baboons, American Journal of Primatology, 2011, 73, 1160-1168.

Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses

Redox-active transition metal ions, such as iron and copper, may play an important role in vascular inflammation, which is an etiologic factor in atherosclerotic vascular diseases.

Tetrathiomolybdate (TTM), a highly specific copper chelator, can act as an anti-inflammatory agent, preventing lipopolysaccharide (LPS)-induced inflammatory responses in vivo.

Female C57BL/6N mice were daily gavaged with TTM (30 mg/kg body wt) or vehicle control. After 3 wk, animals were injected intraperitoneally with 50 µg LPS or saline buffer and killed 3 h later.

Treatment with TTM reduced serum ceruloplasmin activity by 43%, a surrogate marker of bioavailable copper, in the absence of detectable hepatotoxicity.

The concentrations of both copper and molybdenum increased in various tissues, whereas the copper-to-molybdenum ratio decreased, consistent with reduced copper bioavailability.

TTM treatment did not have a significant effect on superoxide dismutase activity in heart and liver.

TTM significantly inhibited LPS-induced inflammatory gene transcription in aorta and heart, and significantly inhibited LPS-induced increases of serum levels.

Similar inhibitory effects of TTM were observed on activation of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) in heart and lungs.

Copper chelation with TTM inhibits LPS-induced inflammatory responses in aorta and other tissues of mice, most likely by inhibiting activation of the redox-sensitive transcription factors, NF-kappa B and AP-1.

Therefore, copper appears to play an important role in vascular inflammation, and TTM may have value as an anti-inflammatory or anti-atherogenic agent

Wei, Hao, Frei, Balz, Beckman, Joseph SULFUR., and Zhang, Wei Jian, Copper chelation by tetrathiomolybdate inhibits lipopolysaccharide-induced inflammatory responses in vivo, American Journal of Physiology-Heart and Circulatory Physiology, 2011, 301, H712-H720.