Ingaba i-methylene blue ibangela umhlaza? Ubungqina betoxicology

I-methylene blue ibonise iimpawu zamathumba kuvavanyo lwezilwanyana lwexesha elide kunye neziphumo ezilungileyo kuvavanyo oluninzi lwaselabhoratri lomonakalo kwimathiriyeli yemfuza. Ezo ziphumo zifanele ukuqwalaselwa. Azimiseli ukuba kunokwenzeka kangakanani ukuba umntu abe nomhlaza emva kokuvezwa okuthile.

Uvavanyo lwe-IARC olupapashwe ngo-2016 lwabeka i-methylene blue kwiQela 3, nto leyo ethetha ukuba amandla ayo okubangela umhlaza ebantwini ayengenakuhlelwa. Iqela elisebenzayo lalingenadatha yomhlaza ebantwini kwaye lagqiba kwelokuba ubungqina bezilwanyana bunomda. IQela 3 alithethi ukuba kuqinisekisiwe ukuba ayinabungozi. Ngokufanayo, ukufunyanwa kwesiphumo kwizilwanyana akuthethi ukuba lonke uhlobo lokuvezwa kwabantu lubonakalisiwe njengonobangela womhlaza.

Imibuzo emithathu efuna iimpendulo ezahlukeneyo

Carcinogenicity ibhekisa ekuphuhlisweni kwamathumba. Uphononongo lwexesha elide kwizilwanyana lunokufumanisa iipateni zamathumba emva kokuvezwa okuchaziweyo. Genotoxicity ibhekisa kumonakalo kwimathiriyeli yemfuza okanye kwiziganeko zeselula ezinxulumene nayo. Isiphumo esilungileyo kuvavanyo lwe-mutation sinika isilumkiso, kodwa asibali ngokuthe ngqo iimeko zomhlaza ebantwini. Umngcipheko ebantwini ubhekisa kumathuba okwenzeka komonakalo phantsi kweemeko zokwenene zokuvezwa.

Le mibuzo ifuna imilinganiselo eyahlukeneyo. Ukubala iibhaktheriya ezineenguqu zemfuza, ukuhlola iiseli zegazi zeempuku kunye nokuxilonga amathumba ngexesha lovavanyo lwesidumbu azizizo iziphumo ezinokutshintshaniswa. Kwaye uvavanyo lonyango olubonisa ukuba into ethile yonakalisa iiseli zomhlaza aluqinisekisi ukuba ukuvezwa okuphindaphindiweyo kunokuqalisa amathumba kwizicubu ezisempilweni. Ingxoxo eyahlukileyo malunga ne-methylene blue kuphando lomhlaza ijongana namabango onyango.

Uthelekiso lwezifundo: ukuvezwa okungapheliyo ngokwenene

Uvavanyo oluphambili lwasebenzisa i-methylene blue trihydrate, yafakwa kwi-0.5% aqueous methylcellulose nge-oral gavage, indlela elinganisiweyo yokuyifaka ngetyhubhu iye esiswini. Iqela ngalinye ledosi kuphononongo lwexesha elide laliquka amadoda angama-50 nabasetyhini abangama-50 kuhlobo ngalunye lwesilwanyana. Ukufakwa kwenzeka iintsuku ezintlanu ngeveki kangangeminyaka emibini, ngokwe-ngxelo yophando ka-Auerbach noogxa bakhe.

Itheyibhile igcina izigqibo ze-NTP ezithile kuhlobo ngalunye lwesilwanyana. Amanani aziimiligram zezinto ezavavanywayo ngekhilogram yobunzima bomzimba wesilwanyana ngeentsuku zokunikwa idosi, hayi iingcebiso zabantu. Izilwanyana zedosi engu-zero zafumana i-vehicle.

Imodeli	Amaqela edosi, mg/kg	Indlela kunye nobude	Isigqibo se-NTP kunye nesiphumo esifanelekileyo
Iimpuku ezingamadoda ze-F344/N	0, 5, 25, 50	Oral gavage; iintsuku ezintlanu/iveki; iminyaka emibini	Ubungqina obuthile: ii-adenoma ze-pancreatic islet-cell kunye ne-adenoma/carcinoma ezidityanisiweyo zanda.
Iimpuku ezingabasetyhini ze-F344/N	0, 5, 25, 50	Ishedyuli efanayo	Akukho bungqina bomsebenzi we-carcinogenic phantsi kwezi meko.
Iimpuku ezingamadoda ze-B6C3F1	0, 2.5, 12.5, 25	Oral gavage; iintsuku ezintlanu/iveki; iminyaka emibini	Ubungqina obuthile: i-carcinoma yamathumbu amancinci kunye ne-adenoma/carcinoma ezidityanisiweyo zanda. I-malignant lymphoma nayo kusenokwenzeka ukuba yayinxulumene.
Iimpuku ezingabasetyhini ze-B6C3F1	0, 2.5, 12.5, 25	Ishedyuli efanayo	Ubungqina obungacacanga: ukwanda okuncinci kwe-malignant lymphoma.

“Ubungqina obuthile” ludidi lwe-NTP lwesiphumo sovavanyo esilungileyo esinamandla angaphantsi “kobungqina obucacileyo.” “Obungacacanga” buchaza isiphumo esingaqinisekanga. Ezi ndidi zibonisa amandla obungqina, hayi ipesenti yomngcipheko okanye ukuhlelwa kwamandla ento ebangela umhlaza.

Isiphumo kwiimpuku ezingamadoda sasinganyuki ngokuthe chu njengamanqanaba. I-pancreatic islet adenoma okanye carcinoma yenzeka kwi-4/50 kwizilwanyana zolawulo nakwi-9/50, 14/50 kunye ne-8/50 kwizilwanyana njengoko iidosi zazinyuka. Iphepha elipapashiweyo lichaza ukubaluleka ngokwezibalo kwidosi ephakathi kuphela. Oku kwenza ingcaciso elula yomgca othe ngqo ingachaneki; akubonisi ukuba idosi ephezulu yayikhusela. I-adenoma lithumba elingenabungozi obubi, ngoxa i-carcinoma iyingozi. Isiphumo esidityanisiweyo akufuneki sichazwe ngokungathi lonke ithumba elibaliweyo lalingumhlaza.

Kutheni izishwankathelo ezahlukeneyo zivakala ngathi ziyaphikisana

Ulwazi lwangoku lokumiselwa kwe-PROVAYBLUE luchaza iziphumo ze-pancreas kwiimpuku ezingamadoda kodwa luthi akukho ziphumo ze-neoplastic ezinxulumene nechiza kwiimpuku. Iphepha lophando lithi ukwanda kwe-neoplastic kwiimpuku kwakungabalulekanga ngokwezibalo, nangona liqaphela iindlela ezinyukayo. Nangona kunjalo, i-NTP yanika iimpuku iindidi eziboniswe ngasentla.

Uhlalutyo lwe-IARC lwezifundo zezilwanyana lucacisa umahluko obalulekileyo wezibalo: iziphumo zamathumbu kwiimpuku ezingamadoda zazinemikhwa yedosi ebalulekileyo, kodwa amaqela ngamnye afumene idosi ayengabalulekanga kuthelekiso lwamaqela amabini kunye nolawulo. Ukuvavanya ipateni iyonke kuzo zonke iidosi kwahlukile ekuvavanyeni iqela ngalinye ngokwahlukeneyo. Abafundi kufuneka bagcine umthombo kunye namagama awo endaweni yokushwankathela zonke ezi ziphumo ngokuthi “iimpuku zaba nomhlaza” okanye “uphononongo lweempuku lwalungenasiphumo.” Akukho nanye kwezi enika umlinganiselo womhlaza ebantwini.

Uthelekiso lwezifundo: iziphumo zomonakalo kwimathiriyeli yemfuza

Icandelo le-genetic toxicology le-NTP Technical Report 540 lichaza uluhlu olwahlukileyo lovavanyo. I-S9 ngumxube waselabhoratri onee-enzyme zesibindi osetyenziselwa ukumodela i-metabolic activation. Ubukho bawo abuguquli uvavanyo lweeseli lube luphononongo lokuvezwa komzimba wonke.

Inkqubo yovavanyo	Iimeko zokwenene zokuvezwa	Isiphumo esilinganisiweyo kunye nesiphumo
Uvavanyo lwe-bacterial mutation, ilothe yesibini evavanyiweyo	Salmonella: 0.25–150 µg/plate; E. coli: 0.25–1,500 µg/plate; kunye nangaphandle kwe-rat-liver S9	Ukwanda kwee-mutation kwiintlobo ezavavanyiweyo.
Iiseli ze-Chinese hamster ovary ezikhuliswe elabhoratri	Uvavanyo lwe-sister-chromatid exchange luquke 0.17–2.5 µg/mL ngaphandle kwe-S9, ukuya kwi-5 µg/mL ne-S9; uvavanyo lwe-chromosome-aberration lwasebenzisa 4.7–22 µg/mL	Iziphumo ezilungileyo ze-exchange kunye ne-chromosome-aberration.
Iimpuku ezingamadoda, uvavanyo olukhawulezileyo	Inaliti enye ye-intraperitoneal: 25, 50 okanye 150 mg/kg; iisampulu kwiiyure ezingama-48	Akukho kwanda kwe-micronucleated erythrocytes kumongo wethambo okanye egazini.
Iimpuku ezingamadoda nezingabasetyhini, uvavanyo oluphindaphindiweyo	Oral gavage: 25, 50, 100 okanye 200 mg/kg; iintsuku ezintlanu/iveki kangangeenyanga ezintathu	Akukho kwanda kwe-peripheral-blood micronucleated erythrocytes.

I-micronucleus ngumzimba omncinci owongezelelweyo we-nucleus onokubonisa ukwaphuka kwechromosome okanye ukulahleka kwechromosome ngexesha lokwahlukana kweseli. Uvavanyo olungenasiphumo kwiiseli zegazi luphendula loo mbuzo uthile kwezo seli zithathwe njengeesampulu. Alunakukhuphela ngaphandle zonke iintlobo zomonakalo we-DNA kuwo onke amalungu omzimba. Kwelinye icala, uvavanyo olunesiphumo esilungileyo kwiiseli ezikhuliswe elabhoratri alusixeleli ukuba zeziphi i-concentration ezafikelelwa zizicubu zomntu.

Ulwazi lokumiselwa nalo lubhala le pateni iyonke: uvavanyo lweebhaktheriya kunye neeseli ezikhuliswe elabhoratri olunemiphumo elungileyo, kunye novavanyo lwe-micronucleus kwiimpuku olungenasiphumo. Ukubiza i-methylene blue ngokulula ngokuthi “genotoxic” okanye “non-genotoxic” kususa ulwazi olubalulekileyo kutoliko.

Oku kuthetha ntoni ngokuvezwa komntu

Ezi zifundo aziniki mda wemihla ngemihla oqinisekisiweyo wokhuseleko kumhlaza ebantwini. Ukwahlula idosi yempuku ngomlinganiselo wobunzima bomzimba akuyi kusombulula umahluko ekufunxweni, kwi-metabolism, kwindlela yokufakwa, kubuninzi bokuvezwa okanye kubude bexesha lobomi. Oko kuya kuvelisa isixa esiguqulweyo, hayi ubungqina bokhuseleko.

Uvavanyo lwe-gavage lweminyaka emibini kunye nonyango olufutshane lwe-intravenous oluphantsi kolawulo lwezonyango ziphendula imibuzo eyahlukeneyo. Lo mahluko uthintela ukuguqulelwa ngokuthe ngqo kwamanani; awuzicimi iziphumo zezilwanyana. Uvavanyo oluluncedo luqala ngekhompawundi kunye ne-formulation echanekileyo, isixa, indlela yokufakwa, ubuninzi, ubude kunye nesizathu sokusetyenziswa. “Amathontsi ambalwa” akachazi nokuba yi-concentration okanye umthamo olinganisiweyo.

Ukuba i-methylene blue yafakwa ngenxa yesizathu sonyango, iziphumo zamathumba zodwa azinakumisela ukuba izibonelelo zolo nyango zazidlula imingcipheko yalo. Ukuba kusacingwa ngokusetyenziswa okuphindaphindiweyo ngokuzikhethela, umngcipheko womhlaza wexesha elide ongalinganiswanga akufuneki uchazwe njenge-zero. Imiba ekhawulezayo ngakumbi, kuquka ukusebenzisana namachiza kunye nokuchanabeka kwi-haemolysis, ichazwe kwi-ziphumo ebezingalindelekanga kunye nezimo apho ingafanele isetyenziswe.

Ukuze ufunde ngakumbi, sebenzisa ilayibrari yophando ukwahlula izifundo zabantu kwizilingo zezilwanyana neeseli. Umbuzo ophambili kwiphepha ngalinye kukuba loluphi uhlobo lokuvezwa olwaluvavanywa kwaye sisiphi isiphumo esasilinganiswa ngokwenene.