International Dairy Topics — Volume 13 Number 3 7

by Dr Rüdiger Kratz, Innovad NV,Technical Services - Ruminant.

The entire dairy industry, including con-sulting nutritionists, veterinarians andproducers, all strive to keep their

herd in good health knowing that healthycows will be able to better cope with stress,especially with potentially contaminatedfeedstuffs.

Stress resulting in oxidative stress can neg-atively impact the dairy cow. Moulds andmycotoxins, endotoxins, hidden toxins inthe feed, extra heat, pathogens challenges,environmental issues, changes in diets, tran-sition period and calving all compromise thecow’s immunity and its ability to deal withpossible diseases, causing immune suppres-sion. As a result, higher somatic cell counts,lower milk yield, poorer reproduction per-formance, mastitis and metritis, areobserved.

Moulds are omnipresent. Their main taskin nature is to decompose organic matter.More than 400 mycotoxins have been iden-tified but about 20-30 are frequentlydetected with highly sensitive analyticalmethods (LC/MS-MS) in feed and food inhigher concentrations. The most criticalmycotoxins for ruminants are deoxyni-valenol (DON), zearalenone formed byFusarium spp. and aflatoxin B by Aspergillus.

Fumonisins, ochratoxin A, ergot alkaloids aswell as silage-associated roquefortin C andmycophenolic acid can also be detected.

The formation of mycotoxins undergoessignificant regional and seasonal variationand among other things depends on thenutrient supply, water content in the sub-strate and in the surrounding air, tempera-ture and pH. The optimum conditions formould growth and toxin formation do notnecessarily need to coincide.

Moulds and mycotoxins in feed causechronic, ‘subacute’ problems in dairy cattlethat show up with signs of higher diseaseincidence, reduced fertility or sub-optimalmilk production. This is mediated by the fol-lowing modes of action:! Reduced intake or feed refusal.! Altered microbial growth in the rumen.! Reduced nutrient absorption andimpaired metabolism.! Altered endocrine and exocrine systems.! Suppressed immune function.

Experience from research and practiceindicate that individual actions are not suffi-cient. The best way to eliminate such riskrelated to the concurrent presence of toxiccontaminants along with all other stressesinherent to the cows’ production challengesseems to lay in a combination of actions –the cow metabolic support emphasisingmaintenance and balancing oxidative stressmanagement, the essential organ (livermainly) aid, the stimulation of rumen func-tion and immune response, along with the

reduction of mycotoxins adsorption andtoxins toxicity through their bio-transforma-tion.

Balancing oxidative stress

In biological organisms, such as the dairycow, the antioxidant system and pro-oxida-tive substances (reactive oxygen species(ROS)) are finely regulated at the cellularlevel. Many studies have shown oxidativestress as a fundamental factor of unwantedimmune and inflammatory responses.

Dairy cows, especially in the phase fromgestation to lactation, are susceptible to avariety of diseases. ROS affect the regulationof gene expression, and the antimicrobialactivity of the macrophages. Elevated levelsof ROS damage nucleic acids, proteins andlipids, affecting important physiological func-tions.

Food spoilage and mycotoxins are consid-ered oxidative stress triggers. It is not yetcompletely clear whether this is done bydirect stimulation of the formation of ROSor indirectly by weakening the antioxidantsystem. Presumably, both paths are taken.In most cases, the levels of natural antioxi-dants are reduced due to lipid peroxidationcaused by mycotoxins.

Fumonisin B1 was found to be a stronginducer of malondialdehyde (marker ofoxidative stress, see Fig. 1).

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Finding the dietary solutionto toxins, stress and immunity in dairy cows

Control FumonisinB1

MD

A (n

mol

/mg

of p

rote

in)

Polyphenols

Faeces Urine

excretion

excretion

Bile

Fig. 1. Oxidative activity of fumonisin B1on kidney cells (Abado-Becognee et al1998).

Body tissue

Kidney

Colon

Small intestinede-glycosylation,glucuronidation,

methylationLiver

sulfation, glucuronidation,

methylation

Fig. 2. Metabolism of polyphenols.

0.6

0.4

0.2

0.0

International Dairy Topics — Volume 13 Number 3 9

The antioxidant system of themammalian cell is complex andconsists of proteins, enzymes,vitamins and pro-vitamins, whichare found in the cytosol, mito-chondria or cell membrane.Special secondary plant metabo-lites such as the polyphenols canstabilise the existing system.Polyphenols are a complex groupof substances, which can bedivided into phenolic acids andflavonoids and being subdividedmuch further. They have animportant role in building the cellwalls that protect the plant fromharmful influences such as UVlight and pathogens and areinvolved in the repair of cellular damage.

The absorption of the polyphenols occursmainly in the small intestine (Fig. 2). Theymay be chemically modified, bound on albu-min to become water soluble and reachingthe liver via the portal vein. In the liver,other molecular changes take place, such ashydroxylation, decarboxylation and conjuga-tion, having the polyphenols becomehydrophilic and excreted via the kidneys inthe urine.

Thus, the main sites of action for polyphe-nols are the intestinal mucosa, liver, and kid-ney. The structural variability of polyphenolsis also reflected in their effect. For exampleproanthocyans are very poorly absorbedand their effect remains limited on theintestinal mucosal area.

Flavanones and isoflavones show the bestbioavailability and can exert their antioxidantpotential in blood, liver and kidney.However, the concentrations fall quicklyafter stopping supply, so that constant feed-ing is necessary. The antioxidant potential ofpolyphenols can be measured in relation tovitamin E in Trolox equivalent antioxidantcapacity (TEAC), showing a broad variationof <0.1 to >5.0 mM TEAC per mMpolyphenol. Therefore the usage ofpolyphenols presupposes their effectivenessin terms of absorption and antioxidantcapacity.

Supporting liver function

Crucial organs, like liver, are stressed anddamaged or malfunctioning due to the pres-ence of mycotoxins (aflatoxin and fumon-isin) after absorption, while immunefunction is compromised by most of theother mentioned toxins.

The liver has a very high metabolic activitythat makes it extra vulnerable for oxidativestress by aggressive molecules. In addition,the liver of dairy cows during early lactationis exposed to specific extra stresses. Lowconcentrations of glucose and insulin in theblood and increased influx of free fatty acidslead to fat deposition in the liver. Mouldsand mycotoxins can exacerbate this furtherby reducing feed intake.

Some herbal ingredients have been provento protect the liver. Experience with variousparts of plants or extracts are supported bytrials with cell cultures (in vitro model), ani-mal studies (in vivo model) and clinical trialsin humans.

Rosmary is well known for its strengthen-ing effect on liver functions. Production andflow of bile are stimulated, so that the diges-tion is improved. The glucuronidation ofunwanted molecules is increased, leading toaccelerated elimination via urine and dimin-ishing their potential disease impact.Artichoke leaves are a liver detoxifying andregenerating agent. It is mainly used to treatliver dyspepsia and disease. Main activecomponents are cynarine and other bittersubstances resulting in the regulation of lipiddigestion.

Stimulating rumen function

It should always be considered that myco-toxins will adversely impact rumen environ-ment and activity even before having aneffect on the animals themselves. Decreasesin ruminal motility, on dry matter intake,acid detergent fibre (ADF), starch digestionand on microbial growth are some of theissues seen in animals fed mycotoxin conta-minated diets, directly impacting productionand indirectly initiating other metabolic dis-orders.

Additionally, toxins like aflatoxin anddeoxynivalenol reduces feed intake and byconsequence further suppression of nutrientsupply. In dairy cattle, T2-toxin has beenassociated with intestinal haemorrhages,bloody faeces, gastrointestinal lesions andenteritis, finally disruption the digestiveprocess in the lower part of the digestivetract.

Moulds also produce antibiotics to defendthemselves against other mould and bacte-ria. Fig. 3 shows some antibiotics producedby penicillium and aspergillus spp. present insilages. These antibiotic activities will supressbacterial production in the rumen and leadto decreased feed conversion as well as‘normal’ toxic effects of mycotoxins.

Fermentation extracts can maintain rumen

functioning and performanceeven in the presence of myco-toxins. They supply micro-nutrients like B vitamins, branch-chained fatty acids and oligopep-tides to a variety of bacteria andprotozoa and stimulate theirgrowth and efficiency actingtherefore as prebiotics.

Cellulolytic bacteria are espe-cially supported and may beincreased in numbers by about50%, bacteria +15%. As a result,the digestibility of organic mat-ter, ADF and hemicellulose areimproved. The production ofshort-chain fatty acids can beincreased indicating higherenergy supply from feed fibre.

Supporting immune function

Mycotoxins appear to have a significantimmunotoxic potential, depending on thedegree of exposure. Gliotoxin produced byA. flavus acts as an immunosuppressive,being antibacterial and improving apoptosis.These effects can be enhanced further by T-2 toxin, as it inhibits phagocytosis of A. fumi-gatus conidia by macrophages. Direct effectsof T-2 toxin are seen in lower concentra-tions of plasma immunoglobulin, and pro-tein. Cows in phases of stress as in earlylactation or due to high temperatures areparticularly susceptible to mycotoxinsbecause their immune system is alreadyovertaxed.

The interactions between the immune sys-tem and nutritional status or requirementsare well documented. The requirement ofthe immune system is highly dependent onthe immune response and applied condi-tions. The system is less stressed when vitalorgans such as the liver are fully functional.

The rumen has great potential to eliminatetoxins, if the microflora is well balanced andvery active. In addition, the immune systemcan be activated directly. b-glucans, asextracted and concentrated yeast cell walls,can activate leukocytes and cytokines.Cytokines are peptides and some regulategrowth and differentiation of cells, othersare mediators of immunological reactions.The stabilisation of the immune systemresults in fewer cases of mastitis, and lowerconcentration of somatic cell count.

Conclusion

At the beginning of lactation, during highmobilisation of body reserves and with highfeed bypass through the rumen, the cow canbarely cope with an additional burden likemycotoxin contamination. A multi-functionalapproach should be used to maintain and tostabilise the health of the cow naturally.Innovad’s Escent can keep the liver and kid-ney healthy, as well as the rumen highly pro-ductive, resulting in more milk. "

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Fig. 3. Antibiotics produced by Penicillium and Aspergillus spp.

Citrinin

Griseofulvin

Mycophenolic acid

PenicillinAspergillus spp.Penicillium spp.

Penicillinic acid

Penitrem A

Roquefortine

Fumagillin