The data indicate that antibiotics &Ad sulfa drugs 1-,:ess plamn cholesterol levels of chicks fed a chclestro- dit w wei they also stimulate gro+,wh, but are without ...
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INFLUENCE OF ORALLY ADMINISTERED ANTIBIOTICS ON GROWTH AND PLASMA LIPID LEVELS OF GROWING CNICKS REPORT 276 12 MAR. 1963
DIJC
409 503'
QUALIFIED REQUESTORS MAY OBTAIN THIS REPORT FROM
UNITED
S TATES
"j9D COPIES OF
ASTIA
ARMY
MEDICAL RFE1ARCH AND DEVELOPMENT COMMAND
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AID NW3UM LABOAIM
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1 Mhala 1963 29
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Gilleit A. JeLfLUGS Ph.D.
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1-2 Nabr~h :i963
Repor't No. 276 ProJect No. 3A025 0 813-03 Subproject No. 2, Workp:hae 24
fIFLUMOB OF ORALLY ADMDI.ST--' ) ANTIBWTICS ON GROWTH AND PLAWA LIPID LKYKB OF GROMG CHICKM
To determine the influence of orlly admnisteea
"i
i-
on pasm lipids of grow r g chicks. SUNKARY: Growing chicks were fed seni-purified diets supplemental
1irh
antibiotics or sulfa drugs in the presence o absenca of s,A,.! cholesterol.
e*x1.
The data indicate that antibiotics &Ad sulfa drugs 1-,:ess plamn cholesterol levels of chicks fed a chclestrodit w wei they also stimulate gro+,wh, but are without effe ct in the absen. e . such a growth stimulatim. In cholesterxl-fed ,,hicks, antibili'Uo and sulfasuxidine elevated plasma cholesterol and lipid ph;sphor-s levels. A highly significant ptsitire eorrelatio7 was observai b 17 ?, -a plasam cholesterol and lipid phospho2'us l-vels for .3hi,-ks f. eit.v '
a cholesterol-free or supplemented diet. APPROMe:
MARION E.
Lt. Colmel,
WD U W
Irec'o -
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INTRODUCTION Recent studies have demcnstrated sn effect .t dietaxy antibiotics on serum cholesterol levels. Nelson et al. (9) o served that the addition of chlortetracycline t, a commercAi ration resulted in increased serum chclesterol and lipids in rabbits. Goldberg and Smith (i)., employing a lw-flat axd a 12.5% cottonseed oil diet, reported that uhlortetra ycline resulted in a slight increase in the plasma cholesterol level cf rabbits receiving the low-fat diet as compared to a decrease in serwm and tissue cholesterol of animals receiving the cott: nseed oil ration. The type of casbohydrate fed also appears t; influence the effect of antibiotics and sulfa drugs on serum choiester l levels. Portmn et al. (10) reportel that succinylsulfathiazole did not alter the serum cholesterol of rats receiving a sucrose diet, but elevated the serun cholesterol levels of rats fed a star.h-ontaining diet. Kritchevsky et al. (5) found -levated ch#.iesterol levels in chicks fed cholesterol when the diet contained glucose as the carbrhydrate source, but not when sucrose replaced glucose. Recently, Howe mnd Bosshaxrt (, I) have stWed the effect of oxytetracycline, chlortetiaycline ani suc-Anylsulfathiaz~ie on plasm cholesterol in the mouse. These autho:,s found an eLevation in plasma cholesterol when oxtetracyc1ine era sucx'inyisulfathAizole were fed in a diet containing saturated frt. cholesterl and cholic acid. When an unsaturated ft- replaei the satu tel fat. xiytetracycline was without effect. Chl.ortetracyciinp under similar : onditions depressed plasma -holeterol. In diets without eded cholesterol, chlortetracycline prduced ivered 1bnlester>..i ve vels zAy in the presence of highly unsaturated fat such as o>d lbrtr :i1 and had no effect in the presence cf less highly unsaturstai fats such as corn oil. In humn subjects, Samuel a&:d Steiner (12) rep rte1 a hyp,-hcolesteremic effect for neamymin. More recently. Steiner et a.. (13) have shown that intramuscularly administered neaycin failed to influence serm chclesterml levels in atheroslerctic patients., and concluded that oral neomycin depresses serum cbolesterol through a local effect on the gastrointestinal tract. The hypvhalestvrnlemlc effect of oral neomycin has been c:rATbordtd (11) and evidence has
been presented which indi.cAtes that the effect -f nemycin is mediated by impairing lipid abscrptim (8). The data to be presented indicate that plasma chlesterl levels of growing chicks are not influe: ed by antibicti s ex ept in situations where they also have a growth-stimulating effet.
1
EXPNITAL Male Hy-Lire chicks were used in two experiments. The chicks were fed a commercial diet for one week prior to receiving the experimental diets. The experimental period was of three weeks' duration in experiment I and four weeks in experiment II. The chicks were housed in heated cages having raised wire floors. The composition of the basal diet used for both experiments is shown in Table 1; the desip of each experiment is indicated in the tables of results (Tables 2 and 3). At the termination of the experimental period, blood sauples
were obtained by cardiac puncture using heparin as an antIc :mgulant. The blood was centrifuged and the plasm tken for chclesteroml, and in experiment II, for lipid phosphorus analysis. Chclesterol and lipid phosphorus were determined by previously described procedures RESULTS All the antibiotics fei in experiment I with the exception of oxtetracycline stimulate grxhth signifivantly (Table 2); oytetracycline also stimulated growth, but the differne ws not estatis-
tically significant. All the treaxents mplc yed did, h wever, significantly depress plasma cholester'. le' . In experiment II. peni.llin. n4my n ar.d as.di0suxidine did not influence growth or plasma lipil levels ,f ahicks fed a hclesterolfree diet. In the chzlesterol-supplmented gmups, h.- w.er, growth was depressed by necmyzin anA sulfasuxidine, artd pl1sma cholesterol and lipid phosphorus were elevated by all trnatments. In Figures 1 and R are presentel the ret-neiship tetveen plasm& cholesterol and lipid phosphorus cf c icks fed a chclesterolfree and supplemented diet,. respectively.
In both cases., a highly
significant (P < 0.01) correlation between these pa~rmeters vas observed, the correlation voe.ffiients being + v.68 %rA.+ .88 for the cholesterol-unsupplemented, and suppiemented. gro'xpsa, respectively. DISCUSSION The results cbtaine- in tVh! -v,' experiment. f -.rhi iks fed a cholesterol-free diet are not in agreemeat. In expe-iment I, antibiotics depressed plasma chclester. while im. eaperiment II they were ineffective. The response in experiment I am probabiy be related to the growth stimulaticr. It hbs been denntrated previously that low-protein diets uni.imi M ,mn. .-. lf~i nt diets .-
which depress growth also elevate plasma cholesterl (7). The growth-stimulating effects cf antibiotics are generally only evident
in animals housed in unclean quarters cr suffering from sublinical infections (2).
The growth stimulation resulting from antibiotic
feeding in experiment I might very well indicate the presence cf such a mild infection which was absent in experiment II. The hypercholesterolemic effect of the antibiotics and sulfa drug fed in experiment II is in accord with findings in cholesterolfed rabbits (9).
The effect of neomycin is in contrast ta its
hypocholesterolemic effect in the human (12). Further studies are necessary to gain a better understanding of the mechanism of actin of antibiotics in altering bl(L~
lipids.
The correlation observed between plasma cholesterol and lipid phosphorus levels is in accord with a previous report (6). These data show a much slower increase in the cholestercl:phosphclipid ratio with increasing plasma cholesterol levels in chicks fed the cholesterol-free diet than in the cholesterol-fed chick. The increase
in lipid phosphorus accompanying plasma choe sterol levels aan be interpreted to represent a homeostatic mechanism which the animal appears capable of maintaining in an endogenous hyper-cholesterolemis. However, in an exogenous hypercholesteralemis resulting from cholesterol feeding, the increase in cholesterol level is sr great and
rapid that the animal cannot ma!intain the =nstsnoy cf the cholesterol: lipid phosphorus ratio. ACKNOWLEMMMT The authors gratefully ackncwiedge the technical assistance of
Messrs. Joseph EUelbroek, Harold Schneider, Wayne G*ai and James Shockley.
S
3
TABLE 1 Composition of Basal Diet
g/100 gm diet
Ingredient Yellow corn meal
34.26
Soyean oil meal
30.84
DL-methionine
0.30
Corn oil
3.00
Salt mixture1
.4.00
Vitamin mixture 2
0.40
.Choline Cl
C.20 to 100.00
Glucose
1 Chick salt mixture, supplied per kg of diet when fed at the rate of 5.31%of the diet: (in grams) CaWO3 . 3.0; Ca3 (4)2, 28.0; K20i4O 9.0; MgSOW4, 1.25; Fe gluconate, 2.24; NaCl., 8.80; and (in milligrams) zno4.2, 60; KI, 40; CuBO4, 20; H3BO3 , 9; CoSO4.7H20, 1; MnWs4, 650. 2 Chick vitamin mix, supplied in mg/kg of diet vhen fel at the rate of 0.40% of the diet; thiamine.HCl, 25.0; riboflavin, 16.0; Ca pantothenate, 20.0; pyridoxine; 6.0; biotinp 0.6; folio acid, 4.0; p-sminobenzoic acid, 2.0; menadione., 5.0; and vitamin B12, 20 pg; inositol, 100; ascorbic aid, 250; niacin, 150; vitamin A, 10,000 IU; vitamin D3 , 1,000 ICU; a-to,opheryl acetate, 100 Mg.
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oIbergj, L. and J. P. Smith.
CES The influence of aure.lyn on
the response of the rabbit to cholesterol feeding.
J. Path.
hot. 68: 475, 1954. 2.
grgy, P.
On the role of antibiotics in nutrition and metabolism.
Am. J. Cliin. Nutrition 6: 3.
,466 1958.
Hove, Z. E. and D. K. B:.sshardt. Antibitl"a and p.sm chclesterol in the mouse. J. Nutrition 1. 368, 1960.
4.
Further studies on the effect of
chlortetracynline on plasm cholesterol cf the wenlin g mouse.
Ibid. M: 375, 1960. 5.
Kritchevsky, D.p W. C. Grant, M. J. Fahrenbach., B. A. Riccardi and R. F. J. McCandless. Effect or dietary carbohydrate on the metabolism of cholesterol-i4-C 1 4 in -hickens. Arch. Bio'ham. Biophys. _U: 142, 1958.
6.
Leveille, G. A., J. W. Sh,3kley wad H. E. Saulerlich. Ifluene of dietary factors on plasm lipid relati:iiships in the grw ing
chick.
Prx . S5.
Exp. Biol. Mel. i0: 31,3. 1961.
7.
Influent-e cf dietary pr:etein
level and amino acids on plasm ohclest-a:z J. Nutritin .6: 321, 1962.
of the gr.ing chik.
8.
Leveille, G. A.., R. C. P7well: H. E. &ubeli-.h and W. T. Nundes. Effect of orally and parenteraily administered necrWun ;.n plasma lipids of himan subjects. Am. J. Clir. Nutriti-,n (in press).
9.
Nelson, D.p A. C. Ivy, R. Altschil ard R. Willheim. Effect of aurewuycin en experimental arterbs Aer- is and serum-,-h1,estsrol
levels.
Arch. Pathc.l. 56: 262, 1953.
10. PMorn, 0. W., E. Y. Lawry and D. Bruro. Effeet of dietary carbohydrate on experimentally indu--ed hyperhclestx lemia and hyperbetalixVprteinemia in rats. Pr:&. Sot. ELp. BEil. Med.
21: 321, 1956.
1. Powell, R. influence e=,retion Nutrition
C., W. T. Nunes, R. S. Harling and J. B. Va. he of nonabsor'able antibiotiss on serwa lipids and the of neutral sterols and bile acids. Am. J. Clin. 11: 156, 1962.
7
12. Small P. and A.
teiner.
cholesterol level of man. 193, 1959.
Effect of neomycin on serm
Proc. Soc. Ep. Biol. Ned. 100:
13. Steiner. A., Z. Howard and S. Akgun.
Effect of antibiotics
on the serm cholesterol concentration of patients vith
atherosclerosis.
Circ. 24: 729, 1961.
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