Ionophores for Ruminants Dale A Blasi Northwest Kansas Agent Update November 7 2012 Presentation Outline Introduction Mode of Action Coccidiostat Ionophores for growing cattle Ionophores ID: 374744
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Slide1
Understanding Ionophores for Ruminants
Dale A. Blasi
Northwest Kansas Agent Update
November 7, 2012Slide2
Presentation OutlineIntroduction
Mode of Action
Coccidiostat
Ionophores
for growing cattle
Ionophores
for beef and dairy cows
ToxicitySlide3
What are Ionophores
?
Purified fermentative by-product of a naturally occurring soil-borne bacteria
1
At least 76 known polyether
ionophores.Possess the conventional polyether ring, but will vary in their chemical composition and even to a slight extent, in their biological activityFeed additive that increases average daily gain by improving the energy utilization of feedstuffs2
1Elanco manufacturing data on file. 2Bergen and Bates. 1984. J Anim Sci 58:1465..Slide4
Ionophores approved and marketed for livestock and poultry in the USA
Trademark
Chemical Name
Approved Species
Approved Use
AvatecLasalocidBroilers, Turkeys
Prevention of CoccidiosisBovatecLasalocidCattle and SheepImprove growth and feed efficiency (Cattle)Coccidiosis
control (cattle) and prevention (sheep)
Cattlyst
Laidlomycin
propionate
Confinement, cattle
Improve growth and feed efficiency
Coban
Monensin
Broilers
Prevention of
Coccidiosis
Rumensin
Monensin
Cattle and Goats
Improve growth and feed efficiency (Cattle)
Coccidiosis
prevention and control (cattle) and prevention (goats)Slide5
Ionophores – Mode of Action
An
ionophore
is a compound that makes
cations
lipid soluble thereby disrupting the homeostatic mechanisms responsible for maintaining intra- and extracellular ion concentrations across the cell membrane of ruminal microbe cells.Specifically, ionophores disrupt the exchange of cations (K+ Na+ H+ Ca 2+ and Mg 2+). By doing so, bacteria that are unable to dispose of their protons by other means consequently decline in numbers.
Slide6
Cellulose
Cellulase
enzymes
Starch
Amylase
enzymesSlide7
Rumen
Bacterial
Population Changes
1
1
Adapted from
Dawson and Boling. 1983. Appl Environ Microb 46:160.Slide8
Ionophore
Sensitive & Insensitive Bacteria
1,2
RUMENSIN
SENSITIVE
PRIMARY
FERMENTATION
PRODUCTS
RUMENSIN
INSENSITIVE
PRIMARY
FERMENTATION
PRODUCTS
Ruminococcus
Methanobacterium
Lactobacillus
Butyrivibrio
Lachnospira
Streptococcus
Methanosarcina
Fibrobacter
Acetate
Acetate, methane
Lactate
Acetate, butyrate
Acetate
Lactate
Methane
Acetate
Selenomonas
Bacteroides
Megasphera
Veillonella
SuccinimonasSuccinivibro
PropionateAcetate, propionatePropionate, acetatePropionateSuccinateSuccinate
1Adapted from Dawson and Boling. 1983. Appl Environ Microbio 46:160.2Adapted from Nagaraja, T. G., C. J. Newbold, C. J. Van Nevel & D. I. Meyer. 1997. Manipulation of Rumen. Fermentation. The Rumen Microbial Ecosystem, 2nd edition. Ed: Hobson & Stewart. pp. 538-547.Slide9
Effects of Rumensin on
VFA Percentages in
Fistulated
Cattle on Pasture
(Molar Percent in Rumen)1
Acetic
Butyric
0 mg 50 mg 200 mg
Monensin
67
63
60
10
11
9
0 mg 50 mg 200 mg
Monensin
1
Richardson
et al., 1976. J. Anim. Sci. 43:657.
Propionic
0 mg 50 mg 200 mg
Monensin
21
22
28Slide10
Effect of ionophore on ruminal fluid parameters
of steers grazing winter wheat, OSU
Item
Control
a
Rumensin®
Bovatec®
SE
b
Control vs Ionophore
c
Rumensin® vs Bovatec®
No. of cannulated
cattle
4
4
4
-------Ruminal fluid analysis-------
PH
5.62
5.70
5.64
.037
.33
.37
NH
3
, mg/100 ml
47.90
51.88
51.24
2.317
.23
.85
Total VFA’s, mmol/l141.37144.33145.813.100.36.74Acetate, mol/100 mol60.6959.56
61.50.731.87.09Propionate, mol/100 mol19.2122.0518.43.614.20<.01Butyrate, mol/100 mol14.0611.5113.86.456.04<.01
A/P ratio3.182.733.35.114.32<.01a Least square means for each collection period.b Standard error of least squares means.c P-value associated with orthogonal contrasts.Slide11
Carbohydrate Digestion by Rumen Microbes
& VFA Efficiency
1
1
Adapted from
Nagaraja, T. G., C. J. Newbold, C. J.
Van Nevel & D. I. Meyer. 1997. Manipulation of Rumen Fermentation. The Rumen Microbial Ecosystem, 2nd edition. Ed: Hobson & Stewart. pp. 538-547.Slide12
Efficiency of Energy Conversion
1
1
Adapted from
Nagaraja, T. G., C. J. Newbold, C. J. Van Nevel & D. I. Meyer. 1997. Manipulation of Rumen Fermentation. The Rumen Microbial Ecosystem, 2nd edition. Ed: Hobson & Stewart. pp. 538-547.Slide13
Rumensin Mode of Action — Summary
Alters rumen microbial populations
New population produces more propionate
Propionate is a more energy- efficient fuel source for cattleSlide14
Ionophores - CoccidiostaticSlide15
Anticoccidials — Mode,
Stage of Action & Minimum Dose Requirements
1-6
1
Ernst,
J. V. & G. W. Benz. 1986. Intestinal Coccidiosis in Cattle. Veterinary Clinic of North America: Food Animal Practice. 2:283.2Long, P. L . & T. K. Jeffers. 1982. Studies on the Stage of Action of Ionophorous Antibiotics against Eimeria
. J Parasitol 68:363.3Radostits, O. M. & P. H. G. Stockdale. 1980. A Brief Review of Bovine Coccidiosis in Western Canada. Can Vet J
24:227.
4
Smith,
C. K.
II &
R. B.
Galloway. 1983. Influence of
Monensin
on
Cation
Influx and Glycolysis of
Eimeria
tenella
Sporozoites
In vitro.
J
Parasitol
69:666.
5
Smith,
C. K. II, R. B. Galloway & S. L . White. 1981. Effect of Ionophores on Survival, Penetration and Development of Eimeria tenella Sporozoites In vitro. J Parasitol
pp. 67:5116Smith C. K. II & R. G. Strout. 1979. Eimeria tenella: Accumulation and Retention of Anticoccidial Ionophores by Extracellular Sporozoites.
Expr. Parasitol. pp. 48:325.aAvailable in dry & liquid formulations for use in feed or water applications for beef & dairy calves.
Monensin
LasalocidAmproliumaDecoquinateTrade nameRumensinBovatec
Corid®Deccox®Cidal/StaticCidalCidal
CidalKilling stages3310Minimum required dose, mg/
lb BW/d0.140.4552.27 0.227Active ingredient
StaticSlide16
Ionophores for Growing CattleSlide17
Southeast Kansas
Rumensin
Mineral
G
razing
Study1 2-Year Average 1996/1997
No. head
No. pastures
Initial wt,
lbs
Daily gain,
lbs
Total gain,
lbs
Mineral intake, oz/d
M
onensin
intake, mg/
hd
/d
Difference
0.19
19
1.6
Rumensin
229
7
552
2.66
b
262b
3.4b 170Control240 7545
2.47a243a 5.0a a,bMeans within a row without a common superscript differ (P < 0.05).
1Brazle, F. K. & S. B. Laudert. 1998. Effects of Feeding Rumensin® in a Mineral Mixture on Steers Grazing Native Grass Pastures. 1998 Cattlemen’s Day Report of Progress 804, Kansas State University Agricultural Experiment Station and Cooperative Extension Service, p. 123-125. http://www.ksre.ksu.edu/library/lvstk2/srp804.pdf.Slide18
Oklahoma
Wheat
P
asture
Rumensin
Mineral Studies4-Year Summary
Control
Rumensin
Horn 1999–2000
1
1.33
1.63
Horn 2000–2001
1
2.55
2.70
Fieser
2004–2005
2
1.21
1.58
ADG, lbs
Fieser
2005–2006
2
2.40
2.53
Improvement
lbs/
hd
/d (%)
0.30
(23%)
0.15 (6%)
0.37
(31%)
0.13 (5%)OSL0.040.030.030.35
4-Year Summary21.802.020.22 (12%)0.01
1Horn, G., C. Gibson, J. Kountz & C. Lundsford. 2001. Two-Year Summary: Effect of Mineral Supplementation With or Without Ionophores on Growth Performance of Wheat Pasture Stocker Cattle. Proceedings from the Wheatland Stocker Conference. pp. A1-A19. (Elanco Trial Nos. T1FB50002 & T1FB50102).2
Fieser,
B. G., G. W.
Horn &
J. T.
Edwards. 2007. Effects of energy, mineral supplementation, or both, in combination with
monensin
on performance of steers grazing winter wheat pasture. J. Anim. Sci. 85:3470-3480.Slide19
Effect of mineral medication
treatments on stocker performance, KSU Stocker Unit
Treatment
Aureomycin + Bovatec
Rumensin
SEM
Mineral intake, oz/hd/d
4.22
a
2.39
b
0.01
Feed Additive
intake, mg/hd/d
325/186
105
On-test
stocker weight, lbs
583
582
4.1
Off-test stocker weight, lbs
739
743
5.3
90-day daily gain
1.73
1.79
0.06
a,b
Means within a row with different superscripts
differ by (P<0.01).Slide20
2010 results, KSU Beef Stocker Unit
Item
Control
Rumensin
Rumensin
Onwt
, lbs657659
660
Offwt
,
lbs
823
842
863
ADG
2.14
2.36
2.62
Intake
.36
.23
.20
Conc
: RM
gm
/ton
400
800
Conc:CTC
1400Slide21
Bovatec
2.2
–
44-pound block
– Contains 2.2 grams
lasalocid sodium per pound (4,400 g/ton)– For use continuously on a free-choice
basis0.43 – 1.45 oz/head/day consumption delivers 60 – 200 mg Bovatec/head/daySlide22
Rumensin
for
Mature Beef Cows
Only
ionophore
approved for use in mature, reproducing beef cowsImproves feed efficiency, which helps maximize profitability
Maintains body condition on 5% to 10% less feedSlide23
Four-trial dose titration, summary of cow weight change and feed intake data
Rumensin, mg/hd/d
Item
0
50
200
Number of cows
108
99
109
Initial wt, lbs
1,063
1,050
1,049
Final cow wt, lbs
1,016
1,006
1,010
Wt. change, lbs
-47
-44
-39
Feed intake (lbs DM/day/exp unit)
0-171 days
164.2
a
155.7
b
146.4
b
Percent of control
100
94.8
89.2
Avg days on study at calving124123125Days from calving to conception93c87d87dNumber of cows bred9993100Number of cows conceived908697Percent conception90.992.597.0
a,b Means within a row with different superscripts differ by (P<0.01).c,d Means within a row with different superscripts differ by (P<0.01).Slide24
Rumensin
for Mature Beef Cows —
Reproductive Safety
1
2007 Trial
0
200
12
12
Conception
date
3
161
a
155
b
Calf to conception, days
90
a
85
b
Calving
percentage
4
(%)
80.7
a
91.9
b
1
Bailey et al., 2007. Can. J. Anim. Sci. 88:113.
2
Pasture was the experimental unit, and each pasture contained 9 to 11 cow-calf pairs.
3
Julian calendar date.4Logistic regression analysis.No. pastures2 Monensin, mg/hd/da,bMeans within a row without a common superscript differ (P < 0.01).Slide25
Effects of
Monensin
on Beef Cow Performance, Oklahoma State University
Study
Supplement
1
ItemCONT
MON
SEM
2
P-value
3
No.
28
28
Initial BW,
lbs
1082
1090
21
0.79
Initial BCS
5.15
5.21
0.10
0.70
Final BW,
lbs
1117
1153
23
0.28
Final BCS
5.285.81
0.140.01Change in BW35.465.110.10.04Change in BCS0.130.570.120.01ADG, lbs/day.621.12.180.041 CONT = 36% CP cottonseed meal based pellet with 0 mg/hd of monensin; MON = 36% CP cottonseed meal based pellet with 200 mg/head of monensin.2 SEM of the Least squares means.3 Observed significance levels
for main effects.Slide26
Ionophore Toxicity Symptoms
Lethargy
Cyanosis
Depression
Pulmonary edema
Myocardial degenerationDeath ….Especially pronounced in horses, where monensin has an LD50 1/100th that of ruminantsSlide27
Estimated
no observed effect level (
NOEL), toxic and lethal dose (mg/kg BW) ranges
Toxic and lethal dose ranges, mg/kg BW
Species
Parameter
Lasalocid
Monensin
Cattle
NOEL
1.0
5 - 30
Toxic range
10 – 100
12 - 20
Lethal dose range
50 – 100
22.4 – 39.8
LD
50
--
26.0
Horses
NOEL
--
--
Toxic range
15 – 20
--
Lethal dose range
>
20
1 - 3
LD
5021.51.4
SheepNOEL----Toxic range45 - 60--Legal dose range> 60--LD
50--11.9SwineNOEL----Toxic range30 - 5040 - 50Legal dose range> 50
--LD50--16.7Slide28
Chronic Rumensin® Toxicity – Trial VPR-255-766
Rumensin (grams/ton)
0
20
60
100
Cattle per treatment
Steers
5
5
5
5
Heifers
5
5
5
5
Mortality (%)
0
0
0
0
Lesions at Necropsy Indicative of Treatment Toxicity
None
None
None
None
Performance Data (160 days)
Average
Daily Gain (lbs.)
1.83
1.89
1.84
1.48
Average Daily Feed Consumption (lbs.)20.418.418.215.3
Feed Efficiency11.189.759.8810.38Mean Rumensin Intake (mg/hd/day)
0184546765Slide29
Summary
Ionophores
are an effective tool for:
I
mproved feed efficiency
Improved rate of gain in stockersSlight improvement in ADG in feedlot cattleDecreased feed intake (which may enhance the carrying capacity of cattle on a given quantity of forage)A potential protein sparing effectIncreased digestibility of low quality foragesSome reduction in the incidence of coccidiosisA decrease in the incidence of lactic acidosisSome reduction in the incidence of feedlot bloatPartial intake regulation in self feeding supplement systemsSome reduction in the incidence of pulmonary emphysemaSlide30
Questions?
Dale A. Blasi
dblasi@ksu.edu