Alteration of GI symptoms in a cow with Johne disease by the dietary organosulfur, 2-mercaptoethanol.

2012·0.09 MB·English

by  Click, Robert E.

LETTERTOTHEEDITOR
Virulence3:6,543–545;October1,2012;G2012LandesBioscience
Alteration of GI symptoms in a cow
with Johne disease by the dietary organosulfur,
2-mercaptoethanol
Robert E. Click
Keywords: 2-mercaptoethanol, dietary organosulfurs, bovine Johne disease, Mycobacterium avium ssp paratuberculosis, MAP, IBS,
ulcerative colitis, Crohn disease, diarrhea, pain
Sub-phenotypesofinflammatoryboweldisease(IBD)—Crohndisease,ulcerativecolitisandsomecasesofirritablebowel
syndrome—aregenerallyconsideredaconsequenceofgastrointestinalinflammationofunknownetiology.Conventional
therapyandmorerecentlybiologicagents,allwithvaryingdegreesofdrawbacks,haveresultedinimprovedcontrolof
thesediseases.However,astheincidenceandprevalencecontinuetorise,needsforprevention,permanentremission
andcuresremainunmet,plustherestillremainneedsforimprovedcontrolofsymptoms,suchaspainanddiarrhea.The
case report herein describes a serendipitous, novel means for curtailing these symptoms associated with a bovine
gastrointestinaldiseasethatmayhaveapplicabilityforpatientswithdiseasescharacterizedbyabdominal-visceralpain
anddiarrhea.
The case report herein describes a seren- Crohn disease,9-13 ulcerative colitis13 and of these diseases have also been found to
dipitous, novel means of curtailing pain irritable bowel syndrome,13 three diseases be altered by organosulfur compounds/
and diarrhea associated with a bovine characterized in whole or part by gastro- derivatives derived from Allium and
gastrointestinaldisease(Johnedisease)that intestinalpainanddiarrhea.Unfortunately, Brassica foods; the most extensively
may potentially be beneficial for relieving the consequences—cause, perpetuate, investigated are processes associated
abdominal-visceral pain and diarrhea in bystander—of such associations are highly withtumorigenesis—anticarcinogenicand
patients with gastrointestinal diseases. controversial and remain to be unequivoc- apoptosis induction.24-26
Johne disease—a world-wide disease allyclarified. Ofalltheprocessesalteredby2-Me,the
primarily in ruminants, most prevalent in The initial investigations on alteration finding that 2-Me altered leukemia pro-
cattle, sheep and goats, but even in ofcellularprocessesby2-Meoriginatedin gression inAKR/Cum mice—astrain that
wildlife—hasmanymanifestationsincom- this laboratory when various murine naturally harbors murine leukemia virus
mon with the human IBD, Crohn disease immunological reactivities in vitro were (MuLV) and at least four ecotropic,
(CD),1-4 including pain and debilitating found to be dramatically enhanced by, or endogenous MuLV proviral DNA
diarrhea (in cattle). As with CD, there are dependentupon,sulfhydrylcompounds— sequences27—was instrumental in why
no preventive/curative therapies for Johne of those studied, the most potent was the protocol reported herein was tested
disease outside a probiotic Dietzia ther- 2-Me.14-17 Subsequently, a number of in incattle.Anadult,four-year-oldmultipar-
apy.5-7TheetiologicagentofJohnedisease situ processes/diseases were found to also ous dairy cow (#16) was found positive
is Mycobacterium avium subspecies para- be altered by 2-Me. For example, 2-Me (sero-specific ELISA OD of 3.85 deter-
tuberculosis (MAP). Natural exposure of (1) reversed the loss of immune functions mined by the Univ Minn Vet Diagnostic
cattle to MAP, which usually results in associated with aging,18,19 (2) increased Lab) for bovine leukemia virus (BLV).
clinical disease at . 2 y of age, occurs longevity and quality of life,19-22 (3) pre- Cattleinfectedwiththisvirusmaydevelop
primarily in utero and/or by oralingestion vented high-fat-diet obesity,21 (4) altered lymphomas/leukemia;28 however, the
of MAP by neonates.8 For disease to be systemiclupuserythematosus,22(5)comple- incidence of disease is quite low relative
manifested,infectionwithMAPisfollowed tely prevented development of mam- to the number of positive animals in any
byintestinalinflammation. mary tumors of unknown etiology23 and given herd, likely because dairy cows in
Interestingly, humans are also system- (6) slowed progression of spontaneous or general are not productive much beyond
ically infected with MAP. However, the cigarette-smoke-induced liver cancers,19,20 5–6 y of age. Twenty-two months after
incidence of infection in the “normal” virally caused mammary tumors23 and #16 tested BLV positive, clinical symp-
population is lower than in those with leukemia (Click RE, in preparation). Some toms indicative of lymphoma developed
Correspondenceto:RobertE.Click;Email:[email protected]
Submitted:08/16/12;Revised:09/05/12;Accepted:09/05/12
http://dx.doi.org/10.4161/viru.22090
www.landesbioscience.com Virulence 543
(lack of appetite, weight loss and enlarged symptoms. This, plus the earlier pretreat- molecule with a chemical structure such
fore-udder lymph nodes). In addition, ment, atypical fecal consistency, indicated that it likely functions via a mechanism
although not having pipestream diarrhea, that retesting for MAP should once again similar to that postulated for 2-Me; i.e.,
her feces were a bit loose, a symptom not be done. Surprisingly, this time she tested generation of sulphane sulfur.31
typical of BLV infection. It should be serologically positive by ELISA (an OD In conclusion, treatment of a cow with
pointed out that these symptoms are in value of 2.4), but was serologically nega- early signs of clinical Johne disease (plus
generalcharacteristicsignsofearly,clinical tive for AGID (a serological test that two cows with BLV-induced leucosis that
Johne disease. However, a diagnosis of defines a more advanced disease than an were negative for Johne disease; manu-
Johne disease was considered unlikely ELISA29) and negative for fecal MAP script in preparation) with 2-Me was safe,
because she had tested MAP negative29 shedding, all determined by Allied just as found in rodents, and it had
multiple times over the prior two years. Monitor, Inc.29 Three weeks after serum ameliorative effects for symptoms of a
Based on the presumptuous diagnosis of and feces were submitted for testing, she bovine intestinal bowel disease. The find-
BLV-inducedleukosisandsincetherewas/ succumbedwithJohnedisease;anticipated ings raise two intriguing questions: By
arenoeffectivetreatmentsforBLVdisease because of the continued weight loss, but what mechanism does intestinal “well-
incattle,shewasconsideredanideal,non- still not understood since treatment cur- being” occur and would IBD patients, if
rodent candidate to assess the safety and tailed diarrhea and reduced GI pain treated with either food or xenobiotic
efficacy of the murine, 2-Me-leukemia sufficiently to return appetite to normal. organosulfurs,haveasimilarhealth-related
protocol. Therefore, she was started on a This is striking because neither of these quality of life benefit?
once daily, feed additive regimen of 1.38 symptoms ever reversed in over 60 end-
mg/kg body weight 2-Me, a dose slightly stage,non-treatedorunsuccessfullytreated Acknowledgments
lower than the lowest effective dose for animals that succumbed from Johne AspecialthankstoDrCraigVanKampen
mice.21Aftertreatmentwasinitiated,both disease.6,7 The results do suggest that for editorial review. This work was sup-
fecal consistency and appetite returned to 2-Me “normalized” the gastrointestinal portedbytheNationalInstitutesofHealth
normal (reduced GI pain?) and both tract in some manner, a result that may (R01AI019643) prior to retirement from
remained normal up until the day she have value for IBD patients. Interestingly, theUniversityofMinnesota,Minneapolis,
succumbed. During this “beneficial” four- a similar phenomenon—decreased mac- MN. NIH and Dr Van Kampen had no
month interval, she unexpectedly contin- roscopic and microscopic colonic involvement in the study design, collec-
uedtoloseweight,whichisnotcharacter- damage—was found for experimentally- tion, analysis and interpretation of data,
istic for BLV-caused leukosis, nor for the induced colitis in rats by dietary me- conclusionsderivedanddecisiontosubmit
Dietzia probiotic reversal of Johne disease thylsulfonylmethane,30 an organosulfur the manuscript forpublication.
References 7. Click RE. Successful treatment of asymptomatic or 12. Hermon-Taylor J. Mycobacterium avium subspecies
clinically terminal bovine Mycobacterium avium sub- paratuberculosis, Crohn’s disease and the Doomsday
1. Clarke CJ. The pathology and pathogenesis of speciesparatuberculosisinfection(Johne’sdisease)with scenario. Gut Pathog 2009; 1:15; PMID:19602288;
paratuberculosis in ruminants and other species. J thebacteriumDietziausedasaprobioticaloneorin http://dx.doi.org/10.1186/1757-4749-1-15
Comp Pathol 1997; 116:217-61; PMID:9147244; combinationwithdexamethasone:Adaptiontochronic 13. Pierce ES. Ulcerative colitis and Crohn’s disease: is
http://dx.doi.org/10.1016/S0021-9975(97)80001-1 human diarrheal diseases. Virulence 2011; 2:131-43; Mycobacterium avium subspecies paratuberculosis the
2. Chiodini RJ, Van Kruiningen HJ, Merkal RS. PMID:21460639; http://dx.doi.org/10.4161/viru.2.2. common villain? Gut Pathog 2010; 2:21; PMID:
Ruminant paratuberculosis (Johne’s disease): the cur- 15647 21167058;http://dx.doi.org/10.1186/1757-4749-2-21
rentstatusandfutureprospects.CornellVet1984;74: 8. Whittington RJ, Windsor PA. In utero infection of 14. ClickRE,BenckL,AlterBJ.Enhancementofantibody
218-62;PMID:6375961 cattle with Mycobacterium avium subsp. paratubercu- synthesisinvitrobymercaptoethanol.CellImmunol
3. ChiodiniRJ.Crohn’sdiseaseandthemycobacterioses: losis: a critical review and meta-analysis. Vet J 2009; 1972; 3:156-60; PMID:5061825; http://dx.doi.org/
areviewandcomparisonoftwodiseaseentities.Clin 179:60-9; PMID:17928247; http://dx.doi.org/10. 10.1016/0008-8749(72)90237-7
MicrobiolRev1989;2:90-117;PMID:2644025 1016/j.tvjl.2007.08.023 15. Click RE, Benck L, Alter BJ. Immune responses in
4. Scanu AM, Bull TJ, Cannas S,SandersonJD, Sechi 9. FellerM,HuwilerK,StephanR,AltpeterE,ShangA, vitro.I.Cultureconditionsforantibodysynthesis.Cell
LA,DettoriG,etal.Mycobacteriumaviumsubspecies Furrer H, et al. Mycobacterium avium subspecies Immunol1972;3:264-76;PMID:4551691;http://dx.
paratuberculosis infection in cases of irritable bowel paratuberculosisandCrohn’sdisease:asystematicreview doi.org/10.1016/0008-8749(72)90165-7
syndrome and comparison with Crohn’s disease and andmeta-analysis.LancetInfectDis2007;7:607-13; 16. Heber-KatzE,ClickRE.Immuneresponsesinvitro.
Johne’s disease: common neural and immune patho- PMID:17714674; http://dx.doi.org/10.1016/S1473- V. Role of mercaptoethanol in the mixed-leukocyte
genicities.JClinMicrobiol2007;45:3883-90;PMID: 3099(07)70211-6 reaction. Cell Immunol 1972; 5:410-8; PMID:
17913930;http://dx.doi.org/10.1128/JCM.01371-07 10. ChamberlinWM,NaserSA.Integratingtheoriesofthe 4645593; http://dx.doi.org/10.1016/0008-8749(72)
5. Click RE. A 60-day probiotic protocol with Dietzia etiologyofCrohn’sdisease.OntheetiologyofCrohn’s 90067-6
subsp. C79793-74 prevents development of Johne’s disease: questioning the hypotheses. Med Sci Monit 17. Peck AB, Click RE. Immune responses in vitro. 3.
diseaseparametersafterinuteroand/orneonatalMAP 2006;12:RA27-33;PMID:16449960 Enhancementofthemousemixedlymphocyte inter-
infection. Virulence 2011; 2:337-47; PMID: 11. BehrMA,KapurV.TheevidenceforMycobacterium action by isologous and homologous sera. Eur J
21701254;http://dx.doi.org/10.4161/viru.2.4.16137 paratuberculosis in Crohn’s disease. Curr Opin Immunol 1973; 3:385-92; PMID:4271347; http://
6. Click RE, Van Kampen CL. Assessment of Dietzia Gastroenterol 2008; 24:17-21; PMID:18043227; dx.doi.org/10.1002/eji.1830030703
subsp.C79793-74fortreatmentofcattlewithevidence http://dx.doi.org/10.1097/MOG.0b013e3282f1dcc4
ofparatuberculosis.Virulence2010;1:145-55;PMID:
21178433;http://dx.doi.org/10.4161/viru.1.3.10897
544 Virulence Volume3Issue6
18. ChangMP,TanakaJL,Stosic-GrujicicS,Yamamoto 23. Click RE. Dietary mercaptoethanol prevents or delays 29. Click RE, Van Kampen CL. Comparison of ante-
EK, Perkins EH, Strehler BL, et al. Restoration of spontaneousmurinemammarytumorigenesis.Submitted. mortem assays to assess progression/regression of
impaired immune functions in aging animals. VI. 24. MilnerJA.Mechanismsbywhichgarlicandallylsulfur paratuberculosisinindividualdairyanimals.Virulence
Differential potentiating effect of 2-mercaptoethanol compounds suppress carcinogen bioactivation. Garlic 2010; 1:134-44; PMID:21178432; http://dx.doi.org/
on young and old murine spleen cells. Int J andcarcinogenesis.AdvExpMedBiol2001;492:69- 10.4161/viru.1.3.10896
Immunopharmacol1982;4:429-36;PMID:6982245; 81;PMID:11480676;http://dx.doi.org/10.1007/978- 30. AmirshahrokhiK,BohlooliS,ChinifroushMM.The
http://dx.doi.org/10.1016/0192-0561(82)90017-0 1-4615-1283-7_7 effect of methylsulfonylmethane on the experimental
19. Heidrick ML, Hendricks LC, Cook DE. Effect of 25. El-BayoumyK,SinhaR,PintoJT,RivlinRS.Cancer colitisintherat.ToxicolApplPharmacol2011;253:
dietary 2-mercaptoethanol on the life span, immune chemopreventionbygarlicandgarlic-containingsulfur 197-202; PMID:21463646; http://dx.doi.org/10.
system,tumorincidenceandlipidperoxidationdamage and selenium compounds. J Nutr 2006; 136 1016/j.taap.2011.03.017
in spleen lymphocytes of aging BC3F1 mice. Mech (Suppl):864S-9S;PMID:16484582 31. TooheyJI.Sulphanesulphurinbiologicalsystems:a
AgeingDev1984;27:341-58;PMID:6334792;http:// 26. CooperAJL,KrasnikovBF,NiatsetskayaZV,PintoJT, possibleregulatoryrole.BiochemJ1989;264:625-32;
dx.doi.org/10.1016/0047-6374(84)90057-5 CalleryPS,VillarMT,etal.CysteineS-conjugateβ- PMID:2695062
20. BeregiE,RegiusO,RajczyK,BorossM,PénzesL.Effect lyases:importantrolesinthemetabolismofnaturally
ofcigarettesmokeand2-mercaptoethanoladministration occurringsulfurandselenium-containingcompounds,
onage-relatedalterationsandimmunologicalparameters. xenobioticsandanticanceragents.AminoAcids2011;
Gerontology1991;37:326-34;PMID:1662659;http:// 41:7-27;PMID:20306345;http://dx.doi.org/10.1007/
dx.doi.org/10.1159/000213280 s00726-010-0552-0
21. ClickRE.Obesity,longevity,qualityoflife:alteration 27. Buckler CE, Staal SP, Rowe WP, Martin MA.
bydietary2-mercaptoethanol.Virulence2010;1:509- Variationinthenumberofcopiesandinthegenomic
15; PMID:21178502; http://dx.doi.org/10.4161/viru. organization of ecotropic murine leukemia virus
1.6.13803 proviral sequences in sublines of AKR mice. J Virol
22. ClickRE.LongevityofSLE-pronemiceincreasedby 1982;43:629-40;PMID:6287036
dietary2-mercaptoethanolviaamechanismimprinted 28. Kirk JH. Bovine Leukemia UC Davis Veterinary
withinthefirst28daysoflife.Virulence2010;1:516- Medicine Extension. www.vetmed.ucdavis.edu/vetext/
22; PMID:21178504; http://dx.doi.org/10.4161/viru. INF-DA/INF-DA_BovineLeukemia.html.
1.6.13805
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