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Study on toxicity of 999 Ganmaoling grain and influence of diet on hepatic toxicity

999感冒灵颗粒及组分对小鼠急性毒性和饥饿状态下肝毒性影响的研究



全 文 :2016
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Vol41,No.8 April,2016

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Studyontoxicityof999Ganmaolinggrainandinfluenceof
dietonhepatictoxicity
GUOQiuping1,XUTingting2,CHENYanqing1,ZHENYingying2,ZHANGYuefei3,YEZuguang4,JINRuomin2
(1.DrugNonclinicalEvaluationandResearchCenter,GuangzhouGeneralPharmaceutical
ResearchInstitute,Guangzhou510240,China;
2.DrugSafetyEvaluationCenter,ShanghaiUniversityofTraditionalChineseMedicine,Shanghai201203,China;
3.ResearchCenter,HuarunThreeNinePharmaceuticalLimitedByShareLtd.,Shenzhen518110,China;
4.InstituteofChineseMateriaMedica,ChinaAcademyofChineseMedicalSciences,Beijing100700,China)
[Abstract] Thispaperwasaimedtocomparetheacutetoxicityof999Ganmaolinggrainanditsdiferentingredients,andinvestigate
theinfluenceofroutinedietonthehepatictoxicityinducedbyGanmaolinginmice,soastoprovideexperimentalbasisfortheclinical
safetyevaluationMiceweregivenasingledoseofGanmaolinggrainoritsdiferentingredientsrespectivelybygavage,andthenob
servedfor14daysLD50valuesofGanmaolinggrainoritschemicalingredientandthemaximaltolerateddoseofitsherbingredient
weredeterminedMiceweredividedintostarvationanddietgroup,asingledoseofGanmaolinggrainwasadministeredbygavage
·7931·
2016
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Vol41,No.8 April,2016
LD50valueswereestimatedafter14dayobservationMiceweredividedintostarvationanddietgroupAtthesametime,controlgroup
wassetupforeachAsingledoseofGanmaolinggrainwasgivenSerumbiochemicalindexesweredetected,liverweightindexwas
calculatedandlivertissuemorphologicalchangewasobservedafter6hLD50valueswere442,064g·kg
-1forGanmaolinggrain
groupandchemicalingredientgroup,respectivelyThemaximaltolerateddoseoftheherbingredientgroupwascloseto2424g·
kg-1.ThetoxicsymptomwasbasicalysimilarintheGanmaolinggrainandthechemicalingredientgroupThebodyweightandfood
intakeweredecreasedtoacertainextentinbothgroupsTherewerepathologicalchangesofliverandhearttissueinsomeofthesurvi
vinganimalsTheanimalsintheGanmaolinggraingroupexhibitedalightertoxicityandrecoveredfasterthanthatinthechemicalin
gredientgroupLD50valuesofGanmaolinggrainwere256,693g·kg
-1forstarvationanddietgrouprespectivelyTD50valueswere
129,631g·kg-1forstarvationanddietgrouprespectivelyThetoxicityof999Ganmaolingwasless,whichmayberelatedtothe
reductionoftoxicityafterthecombinationofherbandchemicalingredientsComparedwithstarvationgroup,thevaluesofLD50and
TD50ofdietgroupwassignificantlyincreased,andtoxicitywasdecreasedFromthepointofviewofsafety,itissafertouseGanmaol
ingintheabsenceofhungeroraftermealTheabovetestsprovideexperimentalbasisfortheclinicalsafetyuseofGanmaoling
[Keywords] Ganmaolinggrain;ingredient;acutetoxicity;livertoxicity;starvation;diet
doi:10.4268/cjcmm20160806
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·9931·
2016
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Vol41,No.8 April,2016
+
1 
‰Š‹ÒU´µîŠ´,&ÉÛSµ@+
Table1 AnimaldeathcausedbysingledoseadministrationwithGanmaolinggrainoritsdiferentingredients
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6h
8 Ó

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420 3 2 0 0 5(3/2) 50
357 2 0 2 0 4(4/0) 40
303 0 1 0 0 1(1/0) 10
258 0 0 0 0 0 0
_,
096 6 2 0 0 8(3/5) 80
082 5 1 0 1 7(5/2) 70
069 4 1 0 0 5(3/2) 50
059 4 0 1 0 5(3/2) 50
050 4 0 0 0 4(3/1) 40
043 1 0 0 0 1(1/0) 10
$,
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Table2 TheinfluenceofGanmaolinggrainanditschemicalingredientsonfoodintakeinmice
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/g·kg-1
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Ó

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18 47 60 63 59
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069
ѹ
28 47 48 57 65

11 40 49 61 60
  
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Ó

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Table3 TheinfluenceofGanmaolingGrainanditschemicalingredientsonbodyweightinmice(珋x±s)
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/g·kg-1
¹e
Ó

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Ó

!
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Ó

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/g
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/g
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209±11 195±18 213±24 238±11 307±05

206±13 202±22 233±31 253±19 277±30
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Table4 TheinfluenceofGanmaolingherbingredientsonfoodintakeinmice
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!
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Ó

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/g·d-1
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14
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2424
ѹ
208±15 237±19 261±211) 287±24 333±18

203±14 234±22 244±18 260±26 267±32
¶#

ѹ
208±11 241±26 282±16 305±20 338±24

205±16 225±16 243±19 256±18 261±23
  
g

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n=10;
$,´­Ó

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n=10
£

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n=10,
ѹ
n=9(
+

U
)。
+
5 
‰Š‹$,´µ¶:·m;ÄÂÃ
(珋x±s)
Table5 TheinfluenceofGanmaolingherbingredientsonthebodyweightinmice(珋x±s)
´e
„õ
/g·kg-1
¹e
Ó

!
/g
Ó

!
/g
Ó

!
/g
Ó

!
/g
Ó
14
!
/g
$,
2424
ѹ
208±15 237±19 261±211) 287±24 333±18

203±14 234±22 244±18 260±26 267±32
¶#

ѹ
208±11 241±26 282±16 305±20 338±24

205±16 225±16 243±19 256±18 261±23
  
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S»Ö«´7Á•–
Table6 Comparisonofpathalogicalchangeofthemouseliver,heartandgastrointestinebetweenGanmaolinggraingroupandchemical
ingredientsgroup
´e
ÁƒÁ SƒÁ Ö«Á
+   +   +  
w
  3 5 1 1 0 0 1 0 0
_,
1 6 2 0 2 0 2 0 0
3143 
$,´
 
B

»Ñ¹&ɦ´,ž
6h
8ÛS

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¢}BÌ&ɜgom89

x
ª«´7ƒÃblÛ©

3144 
wÔ_,´Ä•–
 
w
LD50„õ
é
442g·kg-1,
®$x_,õé
073g·kg-1,
Ô
îþ_,´
LD50„õ064g·kg
-1
•

w$Ä_
,õ¯Oó
009g·kg-1,
šŸOó
14%,
l+
7。
+
7 
‰Š‹ÒU´µ:·¸¹º¹B.
Table7 TheacutetoxicitytestresultsofGanmaolingandits
diferentingredientsinmice g·kg-1
´e
LD50 95%ÕvC MTD
w
  442(
x_,
073) 386~505
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064 053~078
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G&É
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332 
ϫ
3321 
¶¨hË_­ƒÃ`=ÄÂÃ
 
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´•
,3540g·kg-1
´:·¨h
ALT
­
4720g·
kg-1
´:·¨h
ALT,AST
øù¯O
(P<001),
f
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(珋x±s,n=10)
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´e
„õ
/g·kg-1 ALT/IU·L-1 AST/IU·L-1 Áƒ`=/%
¶#
- 3730±792 13410±2484 4440±0554
1 0448 3720±847 11990±3392 4490±0284
2 0595 3650±695 11390±2060 4530±0266
3 0798 4860±3394 12770±2669 4430±0261
4 1062 6130±3464 13490±3032 4980±0896
5 1416 972989±10511571) 756611±760011) 5518±12321)
  
g

Ô¶#´Q•
1)P<005,2)P<001(
+
9,10
U
)。
+
9 
œ¶:·¨hË_­ÁƒÃ`=ÄÂÃ
(珋x±s,n=10)
Table9 Theinfluenceofdietontheserumbiochemicalindicatorsandliverweightindexinmice(珋x±s,n=10)
´e
„õ
/g·kg-1 ALT/IU·L-1 AST/IU·L-1 Áƒ`=/%
¶#
- 3730±641 9350±1936 5176±0651
1 1492 3650±530 9450±891 5316±0430
2 2001 3650±470 10630±1886 5437±0448
3 2657 4480±1115 11240±2293 5304±0515
4 3540 5160±11612) 11240±2717 5146±0533
5 4720 5100±6962) 11144±12201) 5187±0451
3322 
¶Á´7ÁèÄÂÃ
 
¶#´
,2001
g·kg-1,2657g·kg-1
´B

G&ÉÁ´7wl[
±Á56ù¾ÿÛ
,3540g·kg-1
´
、4720g·
kg-1
´µeB



G&Éå×Ý4Á´7å¨
ÿÛ

Ô¶#´•

‘føù¹ÚÛ

3323 
Áƒº¹•–
 TD50^•–:¼½´é
1292g·kg-1,95%
ÕvCé
1114~1802g·
kg-1,
œ´é
6306g·kg-1,95%
ÕvCé
4657~0428g·kg-1,
ϫ
TD50æ¼½´Ä49
’

+º¹:

-¼½´
1416g·kg-1
Ôœ´
1492g·
kg-12
YQ¡„õ´Ä䐕–

¼½´¨h
ALT,
AST
­Á´7Á»=øù¯O
(P<005),
l+
10。
+
10 
¼½»œáÎÀ‰Š‹¶:·¨hË_­ÁƒÃ`=ĕ–
Table10 Thecomparisonofserumbiochemicalindicatorsandliverweightindexbetweenstarvationanddietcondition
´e
„õ
/g·kg-1
ALT
/IU·L-1
AST
/IU·L-1
Áƒ`=
/%
Á´7Á
»=
¼½
1416 972989±10511571) 756611±760011) 5518±1232 6/91)

1492 3650±530 9450±891 5316±0430 2/10
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§B_

«ž

Ù?

Ö

¶¯ÄÅ×ƶ:·Áº¹Ä½
.…†
[J].
–_A
,2006,27(9):888.
[3] 
ßoŽ

¦!¢

BQŽ

Ö

¶¯ÄÅ×Æz{Ä:·,
ɹÁºÜÄÎq…†
[J].
$%56ËÉk
,2014,
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_,ɸ¹º¹B.()`{2ôRF…†´

_,É
¸¹º¹B.()`{2ô
[S].2005.
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$,

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$
,

!n,ɸ¹º¹B.()`{2ô
[S].2005.
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ߟ 

ß r

¶r4$Ê,¬öϱrÄÉ2ÔÛÜ
[J].
$Æ,
,2015,46(2):293.
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ñ¡¡

ž¢

Ö

q²‰Š,©°ÊµrHè°,
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–_Ëè&-.
,2011,33(2):77.
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’å“

£F 

Ò!L

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,2014,12(6):512.
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!wõ

B¤B

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[J].
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