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TETRODOTOXIN NGUON GOC VI SINH VAT VA TRIEN VONG LTNG DUNG TRONG Y Dl/OC 6 VIET NAM
Bui Thj Thu Hien', Biii Trong T a m ' , Pham Quoc Long^
I. Viin Nghien cihi Hdi san, Bp Nong nghiip vd Phdi triin nong thon 2. Viin Hod hpc cdc Hap chdt thiin nhien, Viin Khoa hpc vd Cong ngh^ Vi^t Nam
I. G i d l THIEU VE TETRODOTOXIN (TTX)
TTX la mgt chat ran ket tinh mau frang, khong bj hda tan frong nude va cac dung mdi thong thudng, chi tan frong dung moi acid, khong ben frong m6i trudng kiem va moi trudng acid manh [17, 18]. TTX ben vdi nhift, d nhift dg Idn hon 220''C, no chuyen sang mau sam nhung van khong bj nong chay. Trong moi trudng axit, TTX chuyen thanh hgp chat axit hydroclotefrodoic CiiHivOgNsHCl; trong moi trudng kiem, no chuyen thanh hgp chat khdng no la axit anhydrotefrodoic Ci,H]909N3 [17].
TTX la chat co phan tir Idn, co cau fruc dac bift, co lien ket ngi phan tir vdi hemilactal va dugc phan loai nhu la mgt hgp chat aminohydroquinazoline co khoi lugng phan tu 319 [31].
e
CH2OH
Hinh 1. c i u true phan tip cua TTX [30]
Ve cau true, TTX dugc xay dyng fren co sd kit hgp nhimg so lifu tii phan tich tia Rangen, cgng hudng tir, ph6 h6ng ngoai va khii phi. TTX co c6ng thiic ciu tao la CnHnNjOg. Co tfn ggi theo lUPAC la Octalhydro-12-(hydroxymetyl)-2-imino-5,9:7-10a-<^rwer/iano-y0a//-/';,i/
dioxocino[6.5]-dipyrimidine-4,7,10,ll,12-pentol - mot hgp chit him ca dj vong, cd cau friic ludng eye [10].
Phan tir TTX bao gim 6 nhom OH d vj tri C,, C,, Cg, C,, C,o, C „ . 6 mSi vj tri nd co the gan tiiem mgt nhom guanidin la nhom trao d6i difn duong trong vung pH sinh ly. Ciu true cua TTX thay doi lien quan den mgt hay nhilu nhom OH". Chiing cd ai luc vdi.mang t l bao nao la nai CO chiia nhieu kenh van chuyen ion Na". Nghien cihi [10] cho thiy kenh van chuyin ion Na"
b! dong khi dung TTX vdi n6ng dg l,8nM. TTX kh6ng hip thu anh sang bing ngoai vdi X = 1690-2000cm , khong hap tiiy eye dai d budc song tren 220nM frong vimg tir ngoai [17].
II. NGUON GOC SEVH HOC CUA TTX
^ Vin dl nguin glc sinh hgc cua TTX vin con dang dugc franh luan va hifn chua co mgt kit uan chinh xac nao. Co hai gia thuyet vf ngu6n glc cua TTX. Gia thuylt thii nhit cho ring TTX la do mgt tuyen frong co the sinh vat bien tilt ra va gia thuylt con lai cho ring doc t l nay la do VI khuan cgng smh ^di dong vat bifn sinh ra [15, 28]. Tren thyc tl, TTX la san phim kh6ng chi CO a ca noc. Dgc to nay con dugc tim thay d bach Uigc dim xanh (loai da timg gay ngo doc chit
Tieu ban: HOAT C H A T SINH HQC BlfeN 627 ngudi d nhifu nude nhift ddi), mgt so loai sa giong Bic My, Ich dom, mgt s6 dgng vat kh6ng xuong song nhu cac loai sao biln, dc, cua, sam, san la. Cau hoi vi sao dgc td nay co d nhieu loai dgng vat rat khac nhau ve pha hf da din dugc cac nha khoa hgc giai dap.
Matsui (1981) va Watabe (1987) nuoi tiiir nghifm loai ca noc khong dgc Takifugurubripes nhung cd b l sung them dgc t l TTX vao thirc an. Cac kit qua nghien cuu deu cho thay dgc td TTX khdng phai do chinh ca noc tilt ra ma la do ca ndc tich ty dugc qua ngu6n thiic an [27].
Ddng thdi, mgt hudng nghien ciru khac lai phat hien ra ring nhung vi khuan co kha nang sinh Tefrodotoxin song cgng sinh vdi cac dgng vat biln nhu ca noc, bach tugc, cua, 6c... Nam 1990, de khang djnh lai gia thuyet nguIn glc sinh hgc cua TTX, Matsui va cgng sy da tien hanh nuoi hai loai ca ndc, mgt kh6ng dgc Takifugu rubripes (frgng lugng tir 114-178g/con) va mgt co ham lugng dgc cao Takifugu niphobles (frgng lugng tir 69,4-90,9g/con), m6i nhom 10 con, bang loai thiirc an co b6 sung them vi khuin san sinh TTX, Shewanella putrefaciens. Ket qua cho thay, sau mgt thang nuoi, mau gan ciia loai ca noc kh6ng dgc Takifugu rubripes frd nen cd dgc td TTX.
Day la minh chirng dau tien khang djnh vi khuin Shewanella putrefaciens la nguyen nhan khien ca ndc frd len dgc [29]. Vifc phat hifn mat do day dac khuan lac cua vi khuan sinh TTX frong tuyen nude bgt cua bach tugc d6m la mgt bang chimg b6 sung (Hwang va cgng sy, 1989). M6i quan hf cgng sinh giua bach tugc va vi khuan d day dugc cho la: bach tugc tao dieu kifn s6ng (nai an ebon d, m6i trudng sinh san) thuan Igi cho vi khuan, d6ng thdi sir dung dgc td do vi khuan sinh ra nhu mgt thir vu khi ty vf hoac tan cdng hiru hifu bao dam an toan cho d6i ben [8].
Bang 1. Mpt s6 loai vi khuan san sinh TTX da du'g'c phan i^p tip mgt s6 loai sinh vat bien.
STT 1 2 3 4
5 6 7 8
9
10
11
12
Loai vi khu4n Vibrio species
Pseudomonas sp Pseudomonas species Pseudomonas species Vibrio alginolyticus Vibrio alginolyticus Shewanella putrefaciens Alteromonas sp.
Bacillus sp
Pseudomonas sp, va Vibrio sp Vibrio species
Microbacterium
arabinogalactanolyticum, Serratia marcescens. Vibrio alginolyticus 32 chiing thugc Bacillus spp 3 chiing thupc Actinomyces spp 1 chung thugc Vibrio spp Shewanella woodyi vS
Roseobacter sp
Sinh v^t mang RuQt cua xanthid (Atergatis
floridus)
Da ca noc Takifugu poecilonolus Tao do (Jania sp.) Da cua ca noc (Takifugu
poecilonotus)
Rupt ca noc (Takifugu vermicularis vermlcularis) Rupt sap bien
Rupt ca noc (Takifugu niphobles)
Tuyen nuac bpt va cac phan mem khac cua bgch tupc vong xanh (Octopus maculotus)
Rupt ca noc (Takifugu vemicularis radiatus) Han Quoc
Tricng, da va rupt ciia mgt SP Ipai ca noc bien Ca ncc Fugu rubripes
Da ca ncc Takifugu pardalls
Tai ll^u tham khao Noguchi vScs. (1986) [21]
Yasumcto vS cs. (1986) [32]
Yasumoto va cs. (1986) [32]
Yotsu vScs (1987) [33]
Noguchi v ^ c s . (1987) [22]
Narita v a c s . (1987) [20]
TakasI Matsui v^ cs. (1989)[28]
Hwang va cs. (1989) [8]
Myoung-Ja Lee va cs. (2000) [19]
Chun-Fal Yu v^ cs (2004) [7]
Zhenlonp Wu va cs.(2005) [34]
Venmathi Maran va cs. (2007) [6]
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Vi sao ca noc lai co kha nang tin tai dugc khi frong ca thi chira mgt lugng Idn dgc t l TTX?
De tra Idi dugc cho cau hoi nay, ngudi ta da tien hanh nghien cuu cau true gen cua ca noc [1].
Kit qua cho thiy, frong qua trinh phat sinh chiing loai hang trifu nam trudc day, dilm ddt_ bien duy nhit trong mgt gen da lam biln dii thanh phan axit am in ciia mgt protein khien cac 16 nho frong hf thing bom nafri ciia ca noc kh6ng con tuong thich va bj TTX nhan difn va phong toa, khiln cho ca noc mien nhilm vdi dgc t l nay. Sy thay d6i nhd be tren da cho phep ca noc chap nhan vi khuin sinh dgc to TTX vao ca the va tan dyng cac lgi thf ma dgc t6 nay mang lai trong cugc chiln sinh tin [1]. Co chi thich irng kieu nhu vay con gap d nhieu sinh vat khac vdi nhirng dgc t l thin kinh (co kit ciu va co chi tac ddng tuong ty TTX) do cac vi tao bien sinh ra nhu saxitoxin, ciguatoxin. Kit qua nghien ciiu gan day [16] cho thay nhieu chiing vi khuan thudc cac hg Vibrios sp., Pseudomonas spp. va Photobacterium phosphoreum co kha nang sinh dgc to TTX (bang 1).
Nhu vay, vi khuan san sinh TTX co d nhieu loai sinh vat khac nhau. Vay tai sao lai co kha nhieu cac nghien cim phan lap cac vi sinh vat do tir ca noc? Dieu nay dugc giai thich la do ham lugng TTX trong ca noc la kha cao frong khi san lugng ca ndc tren the gidi ciing tuong d6i Idn nen qua trinh danh bat, thu mua ca noc ciing de dang hon cac loai sinh vat khac. Va day la ly do vi sao CO nhieu nghien ciru da chgn ca noc lam vat chii de thyc hifn qua trinh phan lap, nudi cay vi sinh vat san sinh TTX.
6 Vift Nam, cac nghien ciru ve TTX, chu yeu la phan tich dgc to, tach chiet va tinh sach TTX tir cac loai ca noc, cua xanthid, bach tugc... Mgt so nghien cim khac cung da phong doan den nguon g6c sinh hgc cua TTX la tir vi khuan. Nhung mdi chi cd Dd Tuyet Nga (2002) da tien hanh nghien ciru, xac djnh co che san sinh dgc td TTX va ham lugng dgc td trong ca noc. Ket qua nghien ciiu budc dau da xac djnh Tefrodotoxin la dgc td ngoai sinh, co ham lugng rat cao frong miia ca ndc mang frimg, nhat la vao thdi ky tning thanh thyc sinh dye [3].
III. HlTOfNG NGHIEN ClTU SINK TONG HOP TTX TU* VI SINH VAT BEEN
Xu hudng sii dung TTX cho y dugc dang ngay cang pho biln (chii ylu cho san xuat thulc).
U'dc tinh can khoang 1200g TTX cho khoang 2 trifu bfnh nhan chua ung thu trong mgt thang;
400g TTX cho 2 trifu ngudi cai nghifn trong 10 ngay... [25] Nhirng nam trudc day, TTX dugc tach chiet chu yeu tir ca ndc hoac ddng vat bien. Nhung vi ham lugng TTX tir ca ndc rit thip (100kg frimg ca noc dgc mdi tach chilt dugc Ig TTX) nen gia thanh cua TTX rit cao [25]. Hon nua, trir lugng ciia ca noc cung ngay cang giam trong khi nhu ciu tieu thu TTX lai ngay cang tang. De dap img dugc nhu cau cua thj trudng, mgt so nghien ciiu da sinh ting hgp TTX theo phuang phap hoa hgc, nhung gia thanh cua san phim kilu nay khdng kinh t l bing phuang phap tach chiet TTX fryc tilp tir ca noc [25]. Mat khac, vifc phat hien ra nguon g l c sinh hgc cua TTX tir vi sinh vat da md ra mgt hudng nghien ciiu mdi do la sinh tong hgp TTX tir vi sinh vat. No vira CO the chii dgng san xuat TTX frong dieu kifn phdng thi nghifm hoac trong cdng nghifp vdi s6 lugng Ion, vira giam dugc gia thanh, do tinh sach lai cao...
Nam 1987, dl xac minh lai kha nang san sinh TTX cua mgt so chirng vi sinh vat, USIO SIMIDU va cgng sy da tiln hanh nuoi ciy thir nghifm 15 chimg thugc hg Vibrionaceae, 5 chimg thugc gi6ng Alteromonas ya mgt chiing E.coli fren m6i trudng ORI, d nhift do 20°C frong 24-30 gid. Sau khi phan tich bing HPLC, nhom tac gia nay da xac minh dugc 15 chung thugc hg Vibrionaceae co kha nang sinh TTX hoac din xuit TTX. Day cQng la mgt trong nhimg nghien ciru thir nghiem, kiem tra tinh xac thyc ciia cac nghien ciiru trudc da cdng bo [30].
Nam 1995, Kendo Matsumura da nghien ciru tim kilm mdi trudng thich hgp dl vi khuin Vibrio alginolyticus phan lap tir ca noc Fugu niphobles co kha nang san sinh TTX vdi ham lugng cao. Ket qua phan tich cho thiy ham lugng TTX la kha cao: 27,2 MU/ml [12].
Tieu ban: HOAT CHAT SINH HOC B I ^ N 6 2 9
Nam 2007, Venmathi Maran va cgng sy da phan lap dugc hai chung Shewanella woodyi va Roseobacter sp. tir mgt loai chan khdp sing ky sinh tren da ca noc Takifugu pardalis. Tac gia cho rang, cac chiing vi khuan san sinh TTX vdi mgt ham lugng rat nho. Do vay, doi hoi cac nha khoa hgc can phai nghien ciru, sang lgc chiing vi khuin nao co kha nang san sinh TTX vdi ham lugng cao. D6ng thdi, can phai tim ra dugc cac dieu kifn tli uu nhu nhift do, pH, che do dinh dudng, thai gian nuoi u... de vi khuan do tao sinh khii theo y muln. Day chinh la mgt trong nhiing van de ma nhieu nha khoa hgc da va dang cin phai nghien ciru frong thdi gian tdi [5].
Xiao-Jie Wang va cgng sy (2008) da nu6i ciy thir nghifm mgt s i chiing vi sinh vat sinh TTX phan lap tir dgng vat bien chan bung. Ket qua la co mgt s6 vi sinh vat phan lap fren moi trudng ORI, TCBS sinh dgc t6 TTX vdi ham lugng khac nhau. Chiing sinh ham lugng thap nhat la 5ng/g, chiing cao nhat la 184ng/g [31].
Trong ciing nam 2008, Peter Hoi-fii Yu va cgng sy (2008) da sir dung mgt s6 chiing Vibrios sinh TTX da dugc cac nghien cim trudc tim ra, nu6i frong cac dieu kifn thich hgp de thu sinh kh6i cd ham lugng TTX cao. Ket qua that bat ngd khi nhom nghien cim cho rang co the thu dugc tir 0,5g dfn l,5g TTX/1 lit sinh kh6i'vi sinh vat nu6i frong 10 ngay. Dieu nay cho thay frien vgng cho mgt hudng di mdi cho nganh c6ng nghiep san xuat TTX phuc vu cho y dugc [25].
IV. T I E M NANG CUA TTX T R O N G Y-DU*OC
Trong nhiing nam gan day, nhieu nha khoa hgc da nghien cuu tim hifu, khai thac va su dung cac chat cd boat tinh sinh hgc cao tir sinh vat bien nhu: prolactin, oxytoxin, progesteron, estrion, cac axit amin, aldosteron,... va dac bift la cac chat dgc sinh hgc (biotoxin) phuc vu nen Idnh te quoc dan.
TTX la mgt trong s6 cac chat dgc sinh hgc co boat tinh sinh hgc cao (la chat dgc than kinh rit manh), khong chi dugc sir dung trong khoa hgc de nghien ciru sy van chuyen ion Na* qua mang te bao, ma con dugc sir dung de dieu che thu6c gay te, gay me va thu6c kich thich sy boat dgng ciia he tuan hoan, dieu trj mgt so benh hiem ngheo nhu cac bfnh ve tim mach, ung thu, HrV-AIDS, lam thuoc cai nghifn,...
1. Mot so ung dung ciia TTX
Thii nhat, Tetrodotoxin (TTX) co tac dung kich thich boat dgng ciia hf tuan hoan, lam thay ddi nhjp tim, thay d6i truang lyc ciia thanh mach, dan den sy thay d6i huyet ap. Sir dyng TTX vdi lilu lugng l,3.10"^mg/'kg frong vifc phong ngira co hifu qua cac trang thai xa cimg ddng mach va bao che cac loai thu6c dac frj chira bfnh huyet ap, r6i loan nhjp tim [9].
Thir hai, TTX lam giam tinh tham ciia mang te bao d6i vdi vifc van chuyen ion Na* ma kh6ng anh hudng den qua trinh van chuyen ion K*, trong khi do cac thu6c gay te khac lai co tac dung ddi vdi ca 2 kenh van chuyen nay. Dieu nay rat cd y nghTa trong vifc nghien ciru sinh ly mang te bao [11].
Thii ba, TTX dugc diing de dieu che thudc gay te, gay me frong phau thuat. Ngoai nhirng tac dung gay te giong thu6c: novocain, procain, cocain, TTX cd nhieu uu diem ban d kha nang gay te tai cho va tac dung manh ban nhieu so vdi thu6c gay te khac. Vi du: de kim ham boat dgng ciia hf thin kinh bang cocain phai can den n6ng dg 500mg, trong khi do TTX chi cin 0,03mg (hieu qua tac dung ciia TTX manh gap 60.000 lan cocain) [13].
Thir tu, TTX con dugc diing nhu thu6c giam dau, khi sir dung TTX vdi lieu lugng rit nhd cd kha nang cit con dau ciia nhimg bfnh nhan ung thu gan d giai doan cuoi. Cong ty Intemational Wex Technologies (Canada) da sir dung TTX de che ra Tectin (thuoc giam dau), Tocudin (thuoc gay te). va Tefrodin (thu6c cai nghifn ma tuy) - mgt vai loai thulc giiip bfnh
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nhan ung thu vugt qua dugc nhung con dau hoac giiip con nghifn heroin cit con. Cac thii nghifm ban diu khi sir dung thulc cho kit qua kha quan. Theo cac chuyen gia, cac thuoc nay co thi ngan chan tl bao thin kinh chuyin tin hifu dau den nao, chiing khac vdi cac thudc giam dau khac d ch6 no kh6ng gay ra tac dyng phu nhu morphin, khdng xung dgt vdi cac loai thuoc khac va ciing kh6ng gay nghifn [26]. Vift Nam cung da nghien cuu thanh cdng bift dugc TTiien Thanh Hoan sir dung cho cai nghifn ma tuy. Moi vien nhgng Thien Thanh Hoan cd chiia tli da 0,lmiligam TTX va mgt s i vj thulc Dong y khac [4].
Thir nam, nghien cuu cua Lesort cho thiy TTX co kha nang lien ket vdi protein ciia HIV, dac biet la gp-120, do do lam cho genom cua HIV kh6ng the gin vao genom ciia ngudi. Vi v^y, HIV khong thi phat friln thanh AIDS dugc. Day chinh la tin hifu dang mimg cho qua trinh di tim thulc dieu tri can bfnh thi ky HIV-AIDS [14].
2. Mot so tac dung co hai ciia TTX
TTX khong chi co tac dyng c6 lgi, cung nhu nhieu bift dugc khac, neu sii dung nd khong dung each, diing lilu lugng hoac diing myc dich thi se frd thanh dgc dugc, tac hai khdn ludng den sure khoe con ngudi.
Doi vdi hi thdn kinh cua nguai vd dpng vdt, TTX co khd ndng ngan chgn diin thi hogt dgng ciia sgi ca dan den sy thay d6i difn tich Na* fren be mat ciia te bao than kinh, lam cho difn the boat dgng ciia ca bj iirc che va hf th6ng than kinh bj suy yeu. Tiiy vao lieu lugng dgc to TTX nhieu hay it ma gay ra hau qua khac nhau, nhe thi gay cam giac choang vang, non miia, co gi^t dir dgi, sau do bat tinh vai ngay, nang thi rdi loan h6 hap va gay tu vong... [24].
Khi tac dyng vao te bao than kinh, no gi6ng nhu xung difn gay kich thich manh lam hung phan qua miic dan den ion Na* dugc kich thich tao ra vdi mgt lugng du thira frong te bao, ion nay khong dugc van chuyen ra ngoai te bao va tap trung nhieu d phan dau mut day than kinh, dan den anh hudng tdi phan img truyen dan xung cua tf bao than kinh cam giac, dong thdi lam cho mang te bao bj khii eye va kenh van chuyen i6n dong [23].
Tren day la mgt s6 nghien ciru tac dung cd lgi va co hai ciia TTX ddi vdi ngudi va dgng vat. Nhin chung thi hau het cac tac dung co lgi cua TTX doi vdi con ngudi ciing kha rd va noi bat. Vifc img dung TTX frong y dugc da va dang dugc sir dung rgng rai. Song, nhu cau sii dung TTX khong chi d Vift Nam ma fren the gidi cung ngay cang tang, trong khi dd sd lugng TTX dugc tach chift, tinh che tir dgng vat bien, dac bift la ca ndc ciing khdng phai la nhieu.
3. Trien vong sir dung TTX d Vi^t Nam
TTX la thanh phan quan trgng trong cac lifu phap cai nghifn, chira ung thu, HIV hoac sir dyng lam thuoc giam dau. Nhirng nhdm. lifu phap nay tao ra nhu ciu sir dyng TTX rit Idn d Vift Nam va doi hoi mgt nguIn cung cip doi dao nguyen lifu. Theo thong ke nam 2008 ciia Bg Lao dgng, Thuang binh & Xa hgi, Vift Nam cd kh6ng dudi 173.603 ngudi nghifn ma tuy [5]. Gia su de cai nghifn cho s i ngudi nghifn nay; mii ngudi sii dung 2 vien thuoc bift dugc Thien Thanh Hoan frong mgt ngay va qua trinh dilu frj keo dai frong 10 ngay thi nha san xuit phai sir dung it nhat 400 gam TTX dl frgn cimg mgt so vj thuoc Ddng y [5].
De san xuat mgt lugng TTX nhu vay, cin co it nhit 40 tan tning ca ndc dgc [25], hay khoang 4.000 tin ca noc dgc (trimg chilm khoang 5-10% frgng lugng ca ndc). Trir lugng ca noc fren toan viing bien Vift Nam (theo udc tinh nam 2005 [2]) la khoang 37.387 tin. Trong dd hg ca noc Tefraodontidae chilm khoang 84,7% tong trti- lugng. Day la ngudn nguyen lifu tilm tang de tach chiet TTX. Tuy nhien, nguon nguyen lieu nay dang bj chia se bdi viec thu mua cua cac thuang gia Trung Quoc va Han Quic, trong khi Chinh phii Viet Nam vin chua gd bd lenh cim
Tieu ban: HOAT C H A T SINH HOC BI^N 631 khai thac, buon ban, van chuyen va chi biln ca noc. Bdi vay, vifc thu mua, xu ly va chiet xuat TTX tir mgt lugng Idn ca ndc nhu thi la hau nhu kh6ng the thyc hifn, xet ve mat kinh te va xa hgi. Ro rang, ben canh ngu6n nguyen lifu trien vgng la ca noc, can tim kiem nhting ngu6n nguyen lifu khac de san xuat TTX. Trong do, hudng nghifn cim sinh ting hgp TTX tir vi sinh vat noi len la hudng di trien vgng va ben vimg, hiia h?n dap ling dugc nhu cau sir dung TTX ngay cang tang ciia nganh y dugc Vift Nam.
Mau ca noc (gan, trung, ...)
Nudi cay fren dTa thach
Phan lap khuan lac Nu6i sinh khoi
Can te bao
•> '
Pha te bao ' ' Djch n6i
H P L C
• * -
•—
Ly tam
^' Dich n6i
' ' Co chan khong
^ ' Tinh sach bing Bio
Gel, Bio Rex
Thu sinh kh6i
Sa do 1. Phan lap va nuoi cay vi sinh vat san sinh TTX tip ca ndc
Can nhac trien vgng nay, Vifn Nghien ciru Hai san dang tien hanh de tai 2008-2010 ''Nghiin ciru phdn lap, nudi cdy chiing vi sinh vdt sdn sinh Tetrodotoxin (TTX) trong cd noc dpc Viit Nam vd tach chiit TTX\ Den thdi diem hifn tai, de tai da phan lap theo hinh thai khuan lac tren 4 loai m6i truong khac nhau d 4 bg phan ciia 3 loai ca ndc khac nhau, dugc t6ng sd la 130 chiing vi sinh vat. Nhung cung mdi chi nu6i sinh kh6i va kiem tra dgc to TTX tir sinh kh6i dugc 54 chiing, phat hifn co 18 chiing co dgc to TTX, frong do cd 4 chiing thugc Bacellus sp, 3 chiing thugc Actinomyces sp, mgt chiing thugc Vibrio sp, con lai 10 chiing chua phan loai ro (sa do 1).
Bao cao chi tiet mgt sd ket qua da lam dugc ciia de tai se dugc trinh bay trong thdi gian tdi..
V. TAI LEU T H A M K H A O Tai lieu tieng Viet
1.
2.
Nguyin Hiru C6ng, Le Ty Quoc Tuan (2005). Chuan doan difn va ngg dgc ca ndc. Bao cao tai Dai hgi Thin kinh The gidi lan thir 18 tai Sydney - Ausfralia ngay 10/11/2005.
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TETRODOTOXIN PRODUCED BY BACTERIA AND FERSPECTFVE OF USING IN PHARIVIACY AND IVIEDICINE IN VIET NAM
Bui Thi Thu Hien, Bui Trong Tam, Pham Quoc Long SUMMARY
Tefrodotoxin (TTX) was first isolated from ovaries of puffer fish. Since then, it has been commercially exfracted and purified for pharmaceutical drug, being possibly usefial in aiding cancer patients and potential use as a withdrawal formulation for heroin addicts. However, the exfraction rate of TTX is exfremely low, about Ig TTX per 100kg of ovaries of toxic puffer- fishes, making it one of the highest priced natural neurotoxins. In addition, the industry is slowed down as stocks of puffer fish have been falling as the result of over exploitation. The drive to find more economical routes for TTX production is because of its potential as a novel.
In this mini-review, sfrategies toward the total synthesis of TTX fi-om microorganisms are discussed.
