Methylene blue inokonzera gomarara here? Humbowo hwetoxicology

Methylene blue yakaratidza zviratidzo zvemamota muzviedzo zvenguva refu pamhuka uye migumisiro yakanaka muzviedzo zvakati wandei zvemurabhoritari zvekukuvadzwa kwezvinhu zvemajini. Zvakawanikwa izvozvo zvinofanira kutariswa. Hazviratidzi mukana wekuti munhu achaita gomarara mushure mekuratidzwa kwakati.

Ongororo yeIARC yakabudiswa muna 2016 yakaisa methylene blue muGroup 3, zvichireva kuti kugona kwayo kukonzera gomarara muvanhu kwakanga kusingakwanisi kuiswa muchikamu. Boka racho rakanga risina data regomarara revanhu uye rakaona humbowo hwemhuka sehushoma. Group 3 hairevi kuti zvakaratidzwa kuti haina ngozi. Saizvozvowo, zvakawanikwa mumhuka hazviiti kuti kuratidzwa kwese kwevanhu kuve chikonzero chegomarara chakaratidzwa.

Mibvunzo mitatu inoda mhinduro dzakasiyana

Carcinogenicity ine chekuita nekuumbwa kwemamota. Chidzidzo chenguva refu pamhuka chinogona kuona maitiro emamota mushure mekuratidzwa kwakatsanangurwa. Genotoxicity ine chekuita nekukuvadzwa kwezvinhu zvemajini kana zviitiko zvine chekuita nazvo mumasero. Mutation assay ine mugumisiro wakanaka inopa chiratidzo cheyambiro, asi haiverengi zvakananga magomarara muvanhu. Ngozi kuvanhu ine chekuita nemukana wekukuvara pasi pemamiriro chaiwo ekuratidzwa.

Mibvunzo iyi inoda zviyero zvakasiyana. Kuverenga mabhakitiriya ane mutations, kuongorora masero eropa embeva uye kuona mamota panecropsy hazvisi zviyero zvinotsiviwa. Uyewo, kuyedza kwekurapa kunoratidza kuti chinhu chinokuvadza masero egomarara hakuratidzi kana kuratidzwa kakawanda kuchigona kutanga mamota munyama ine utano. Hurukuro yakaparadzana yemethylene blue mutsvakurudzo yegomarara inobata zvirevo zvekurapa.

Kuenzanisa zvidzidzo: kuratidzwa chaiko kwenguva refu

Chidzidzo chikuru chakashandisa methylene blue trihydrate, yakapihwa mu0.5% aqueous methylcellulose kuburikidza neoral gavage, kureva kupihwa kwakayerwa kuburikidza nechubhu kupinda mudumbu. Boka rega rega redose muchidzidzo chenguva refu raiva nevarume 50 nevakadzi 50 verudzi rumwe nerumwe. Kupihwa kwakaitwa mazuva mashanu pasvondo kwemakore maviri, maererano nemushumo wechidzidzo waAuerbach nevamwe.

Tafura inochengetedza mhedziso dzeNTP dzakanangana nerudzi rumwe nerumwe. Huwandu hwacho ihwo milligrams dzechinhu chakaedzwa pakilogram yehuremu hwemuviri wemhuka pamazuva ekupihwa dose, kwete kurudziro kuvanhu. Mhuka dzedose yezero dzakagamuchira vehicle.

Model	Dose groups, mg/kg	Route and duration	NTP conclusion and relevant finding
Male F344/N rats	0, 5, 25, 50	Oral gavage; five days/week; two years	Humwe humbowo: pancreatic islet-cell adenomas uye adenoma/carcinoma zvakabatanidzwa zvakawedzera.
Female F344/N rats	0, 5, 25, 50	Hurongwa humwe chete	Hapana humbowo hwecarcinogenic activity pasi pemamiriro aya.
Male B6C3F1 mice	0, 2.5, 12.5, 25	Oral gavage; five days/week; two years	Humwe humbowo: small-intestinal carcinoma uye adenoma/carcinoma zvakabatanidzwa zvakawedzera. Malignant lymphoma inogona kunge yakabatanidzwawo.
Female B6C3F1 mice	0, 2.5, 12.5, 25	Hurongwa humwe chete	Humbowo husina kujeka: kuwedzera kudiki kwemalignant lymphoma.

“Some evidence” chikamu cheNTP chemugumisiro wakanaka wekuyedza une simba riri pasi pe“clear evidence.” “Equivocal” rinotsanangura zvakawanikwa zvisina chokwadi. Zvikamu izvi zvinoratidza kusimba kwehumbowo, kwete percentage yengozi kana kurongwa kwekuti carcinogen ine simba rakadii.

Mugumisiro wemakonzo echirume wakanga usiri kuwedzera zvishoma nezvishoma senhanho dzemasitepisi. Pancreatic islet adenoma kana carcinoma yakaitika mu4/50 controls uye mu9/50, 14/50 uye 8/50 mhuka pamadose aiwedzera. Pepa rakabudiswa rinotaura statistical significance yedose yepakati chete. Izvi zvinoita kuti tsananguro yakapusa yemutsara wakatwasuka isava yakarurama; hazviratidzi kuti dose yepamusoro yaidzivirira. Adenoma ibundu risiri malignant, nepo carcinoma iri malignant. Endpoint yakabatanidzwa haifaniri kutsanangurwa sokunge bundu rega rega rakaverengwa raiva gomarara.

Nei pfupiso dzakasiyana dzichiita sedzinopesana

PROVAYBLUE prescribing information iripo parizvino inotaura zvakawanikwa zvepancreas mumakonzo echirume asi ichiti hapana drug-related neoplastic findings mumbeva. Pepa retsvakurudzo rinoti kuwedzera kweneoplastic mumbeva kwakanga kusina statistical significance, asi richitaura positive trends. Zvisinei, NTP yakapa mbeva zvikamu zvinoratidzwa pamusoro.

Ongororo yeIARC yezvidzidzo zvemhuka inojekesa musiyano wakakosha westatistics: zvakawanikwa zvemudumbu embeva dzechirume zvaiva nesignificant dose trends, asi mapoka ega ega akapiwa dose akanga asina significance mukuenzanisa pairwise necontrols. Kuyedza maitiro ese pamadose akasiyana kwakasiyana nekuyedza boka rega rega rakaparadzana. Vaverengi vanofanira kuchengetedza source nemashoko ayo pane kupfupisa zvese izvi kuti “mbeva dzakaita gomarara” kana kuti “chidzidzo chembeva chakanga negative.” Hapana chimwe chezvizvi chinopa mwero wegomarara revanhu wakayerwa.

Kuenzanisa zvidzidzo: zviyero zvekukuvadzwa kwezvinhu zvemajini

Chikamu chegenetic toxicology cheNTP Technical Report 540 chinotsanangura seti yakasiyana yezviedzo. S9 musanganiswa wemurabhoritari une maenzyme echiropa unoshandiswa kumodela metabolic activation. Kuvapo kwawo hakushanduri cell assay kuita chidzidzo chekuratidzwa kwemuviri wese.

Test system	Actual exposure conditions	Measured endpoint and result
Bacterial mutation assays, second tested lot	Salmonella: 0.25–150 µg/plate; E. coli: 0.25–1,500 µg/plate; with and without rat-liver S9	Mutations dzakawedzera mumhando dzakaedzwa.
Cultured Chinese hamster ovary cells	Sister-chromatid exchange testing included 0.17–2.5 µg/mL without S9, up to 5 µg/mL with S9; chromosome-aberration testing used 4.7–22 µg/mL	Migumisiro yeexchange neyechromosome-aberration yakanga positive.
Male mice, acute experiment	Single intraperitoneal injection: 25, 50 or 150 mg/kg; samples at 48 hours	Hapana kuwedzera kwemicronucleated erythrocytes mumarrow kana muropa.
Male and female mice, repeated experiment	Oral gavage: 25, 50, 100 or 200 mg/kg; five days/week for three months	Hapana kuwedzera kwemicronucleated erythrocytes muperipheral blood.

Micronucleus chinhu chidiki chekuwedzera chine nuclear material chinogona kuratidza kutsemuka kwechromosome kana kurasika kwechromosome panguva yekupatsanuka kwesero. Blood-cell assay ine mugumisiro negative inopindura mubvunzo iwoyo chaiwo mumasero akatorwa semasampuli. Haikwanisi kuramba mhando dzese dzekukuvadzwa kweDNA munhengo dzese. Ukuwo, cultured-cell assay ine mugumisiro positive haitauri kuti nyama dzemunhu dzakasvika paconcentration ipi.

Prescribing information inonyorawo maitiro aya ese: bacterial ne cultured-cell tests dzine migumisiro positive, uye mouse micronucleus tests dzine migumisiro negative. Kungoti methylene blue “genotoxic” kana “non-genotoxic” kunobvisa ruzivo rwakakosha pakududzira.

Izvi zvinorevei pakuratidzwa kwemunhu

Zvidzidzo izvi hazvipi threshold yezuva nezuva yakasimbiswa seyakachengeteka pagomarara kuvanhu. Kugovanisa dose yemakonzo nebody-weight factor hakugadzirisi kusiyana kweabsorption, metabolism, nzira yekupinda mumuviri, kuwanda kwekuratidzwa kana nguva yehupenyu hwese. Zvingopa huwandu hwakashandurwa, kwete humbowo hwekuchengeteka.

Chidzidzo chemakore maviri chegavage uye kurapwa kwenguva pfupi nemutsinga pasi pekutarisirwa kwechiremba zvinopindura mibvunzo yakasiyana. Musiyano iwoyo unodzivirira direct numerical extrapolation; haubvisi zvakawanikwa mumhuka. Ongororo inobatsira inotanga necompound neformulation chaiyo, huwandu, nzira, frequency, duration uye chikonzero chekushandisa. “Madonhwe mashoma” hazvitauri concentration kana volume yakayerwa.

Kana methylene blue yakapiwa nechikonzero chekurapa, zvakawanikwa zvemamota zvoga hazvigoni kuona kana mabhenefiti ekurapwa ikoko aipfuura ngozi dzako. Kana kushandiswa kakawanda kusiri kwekumanikidzwa kuri kufungwa nezvako, ngozi yenguva refu yegomarara isina kuyerwa haifaniri kutsanangurwa sezero. Nyaya dzinokurumidza kukosha, kusanganisira drug interactions uye susceptibility kuhaemolysis, dzinotsanangurwa muside effects and contraindications.

Kuti uverenge zvakawanda, shandisa research library kusiyanisa zvidzidzo zvevanhu nezviedzo zvemhuka nemasero. Mubvunzo wakakosha papepa rega rega ndewekuti rakayedza kuratidzwa kupi uye rakayera mugumisiro upi chaizvo.