Shin methylene blue na haifar da cutar daji? Shaidar ilimin guba

Methylene blue ya nuna alamun samuwar ƙari a gwaje-gwajen dabbobi na dogon lokaci, kuma ya ba da sakamako mai kyau a wasu gwaje-gwajen dakin gwaje-gwaje na lalacewar kayan gado. Waɗannan sakamakon sun cancanci kulawa. Ba sa tabbatar da yiwuwar cewa mutum zai kamu da cutar daji bayan wani takamaiman fallasa.

Kimanin IARC da aka wallafa a 2016 ya sanya methylene blue a Rukuni na 3, ma'ana ba a iya ware shi a matsayin mai haddasa cutar daji a mutane ba. Ƙungiyar aiki ba ta da bayanan cutar daji na mutane, kuma ta ɗauki shaidar dabbobi a matsayin mai iyaka. Rukuni na 3 ba yana nufin an tabbatar da cewa ba shi da illa ba. Haka kuma, wani sakamako da aka samu a dabba ba ya sa kowane irin fallasar mutum ya zama sanannen dalilin cutar daji.

Tambayoyi uku da ke buƙatar amsoshi daban-daban

Carcinogenicity yana magana ne game da samuwar ƙari. Nazarin dabba na dogon lokaci na iya gano tsarin samuwar ƙari bayan takamaiman fallasa. Genotoxicity yana magana ne game da lalacewar kayan gado ko abubuwan da suka shafi haka a cikin ƙwayoyin halitta. Sakamako mai kyau a gwajin mutation yana ba da alamar gargadi, amma ba ya ƙirga cututtukan daji kai tsaye a mutane. Haɗarin ga mutane yana magana ne game da yiwuwar cutarwa a ƙarƙashin ainihin yanayin fallasa.

Waɗannan tambayoyin suna buƙatar ma'aunai daban-daban. Ƙirga mutant na ƙwayoyin cuta, binciken ƙwayoyin jinin bera, da gano ƙari a necropsy ba su ne ma'aunin ƙarshe ɗaya ba. Haka kuma, gwajin magani da ya nuna cewa wani sinadari yana cutar da ƙwayoyin cutar daji ba ya tabbatar da ko maimaita fallasa zai iya fara samuwar ƙari a lafiyayyen nama. Tattaunawa ta daban kan methylene blue a binciken cutar daji tana magana kan ikirarin magani.

Kwatanta nazari: ainihin fallasa na dogon lokaci

Babban gwajin ya yi amfani da methylene blue trihydrate, wanda aka bayar a cikin 0.5% aqueous methylcellulose ta oral gavage, wato bayarwa da aka auna ta bututu zuwa cikin ciki. Kowace ƙungiyar adadi a nazarin dogon lokaci ta ƙunshi maza 50 da mata 50 daga kowace nau'in dabba. An bayar da sinadarin kwana biyar a kowane mako har tsawon shekaru biyu, bisa ga rahoton nazarin Auerbach da abokan aikinsa.

Teburin yana kiyaye ƙarshen da NTP ya bayar ga kowane nau'in dabba. Adadin milligrams ne na abin da aka gwada ga kowane kilogram na nauyin dabba a ranakun bayarwa, ba shawarwari ga mutane ba. Dabbobin da suka samu adadi sifili sun samu vehicle kawai.

Model	Dose groups, mg/kg	Route and duration	NTP conclusion and relevant finding
Berayen F344/N maza	0, 5, 25, 50	Oral gavage; kwana biyar/mako; shekaru biyu	Wasu shaidu: pancreatic islet-cell adenomas da adenoma/carcinoma a haɗe sun ƙaru.
Berayen F344/N mata	0, 5, 25, 50	Tsari ɗaya	Babu shaidar aikin carcinogenic a ƙarƙashin waɗannan yanayi.
Berayen B6C3F1 maza	0, 2.5, 12.5, 25	Oral gavage; kwana biyar/mako; shekaru biyu	Wasu shaidu: small-intestinal carcinoma da adenoma/carcinoma a haɗe sun ƙaru. Malignant lymphoma ma yana iya kasancewa da alaƙa.
Berayen B6C3F1 mata	0, 2.5, 12.5, 25	Tsari ɗaya	Shaidar da ba ta da tabbas: ƙaruwa kaɗan a malignant lymphoma.

“Wasu shaidu” wani rukuni ne na NTP don sakamako mai kyau na gwaji wanda ƙarfinsa bai kai “bayyananniyar shaida” ba. “Shaidar da ba ta da tabbas” tana bayyana sakamako mara tabbas. Waɗannan rukunan suna bayyana ƙarfin shaida ne, ba kaso na haɗari ko jerin ƙarfin wani sinadari wajen haddasa cutar daji ba.

Sakamakon berayen maza bai kasance yana ƙaruwa a hankali tare da adadi ba. Pancreatic islet adenoma ko carcinoma ya faru a cikin 4/50 na controls da 9/50, 14/50 da 8/50 na dabbobi yayin da adadin ke ƙaruwa. Takardar da aka wallafa ta nuna muhimmancin ƙididdiga ga adadin tsakiya kawai. Wannan yana sa bayanin cewa sakamakon ya ƙaru kai tsaye tare da adadi ya zama ba daidai ba; ba ya tabbatar da cewa mafi girman adadi ya ba da kariya. Adenoma ƙari ne mara cutar daji, yayin da carcinoma ƙari ne mai cutar daji. Ba za a bayyana endpoint da aka haɗa ba kamar dai kowane ƙarin da aka ƙirga cutar daji ne.

Dalilin da ya sa taƙaitattun bayanai daban-daban suke kama da suna cin karo da juna

Bayanin rubuta maganin PROVAYBLUE na yanzu ya ambaci sakamakon pancreas na berayen maza amma ya ce ba a sami sakamakon neoplastic da ke da alaƙa da magani a beraye ba. Takardar binciken ta ce ƙaruwa na neoplastic a beraye bai kai matakin muhimmancin ƙididdiga ba, duk da cewa an lura da positive trends. Duk da haka, NTP ya ba berayen rukunan da aka nuna a sama.

Binciken IARC na nazarin dabbobi ya fayyace wani muhimmin bambanci na ƙididdiga: sakamakon hanji na berayen maza ya nuna significant dose trends, amma kowace ƙungiyar da aka ba adadi ba ta nuna muhimmancin ƙididdiga a pairwise comparisons da controls ba. Gwada tsarin gaba ɗaya a duk adadin ya bambanta da gwada kowace ƙungiya dabam. Masu karatu su riƙe tushen bayani da yadda aka tsara kalamansa maimakon taƙaita duk waɗannan sakamakon zuwa “beraye sun kamu da cutar daji” ko “nazarin berayen ya kasance negative.” Babu ɗayansu da ya bayar da ƙimar cutar daji da aka auna a mutane.

Kwatanta nazari: ma'aunan lalacewar kayan gado

Sashen genetic toxicology na NTP Technical Report 540 ya bayyana wasu gwaje-gwaje daban. S9 wani haɗin dakin gwaje-gwaje ne da ke ɗauke da enzymes na hanta wanda ake amfani da shi wajen kwaikwayon metabolic activation. Kasancewarsa ba ya mayar da gwajin ƙwayoyin halitta zuwa nazarin fallasar jiki gaba ɗaya.

Test system	Actual exposure conditions	Measured endpoint and result
Gwaje-gwajen bacterial mutation, lot na biyu da aka gwada	Salmonella: 0.25–150 µg/plate; E. coli: 0.25–1,500 µg/plate; tare da kuma ba tare da rat-liver S9 ba	Mutations sun ƙaru a strains da aka gwada.
Cultured Chinese hamster ovary cells	Gwajin sister-chromatid exchange ya haɗa da 0.17–2.5 µg/mL ba tare da S9 ba, har zuwa 5 µg/mL tare da S9; gwajin chromosome-aberration ya yi amfani da 4.7–22 µg/mL	Sakamako mai kyau na exchange da chromosome-aberration.
Beraye maza, gwajin acute	Allurar intraperitoneal guda ɗaya: 25, 50 ko 150 mg/kg; samfurori a sa'o'i 48	Babu ƙaruwa a micronucleated erythrocytes a marrow ko jini.
Beraye maza da mata, gwajin da aka maimaita	Oral gavage: 25, 50, 100 ko 200 mg/kg; kwana biyar/mako na watanni uku	Babu ƙaruwa a peripheral-blood micronucleated erythrocytes.

Micronucleus wani ƙaramin ƙarin jikin nucleus ne da zai iya nuna karyewar chromosome ko asarar chromosome yayin rabuwar ƙwayar halitta. Gwajin ƙwayoyin jini da ya ba da sakamako mara kyau yana amsa wannan takamaiman tambayar ne a cikin ƙwayoyin da aka ɗauki samfurinsu. Ba zai iya kawar da yiwuwar kowane irin lalacewar DNA a kowane sashen jiki ba. A gefe guda, gwajin cultured-cell da ya ba da sakamako mai kyau ba ya gaya mana irin concentration da ƙwayoyin jikin mutum suka kai.

Bayanin rubuta maganin ya kuma rubuta wannan tsarin gaba ɗaya: gwaje-gwajen bacterial da cultured-cell sun ba da sakamako mai kyau, yayin da gwaje-gwajen mouse micronucleus suka ba da sakamako mara kyau. Kiran methylene blue kawai “genotoxic” ko “non-genotoxic” yana watsar da bayanan da ke da muhimmanci ga fassarar sakamakon.

Abin da wannan ke nufi ga fallasar mutum

Nazarin ba su bayar da ingantaccen iyakar adadin yau da kullum da aka tabbatar yana da aminci daga cutar daji ga mutane ba. Raba adadin bera da wani body-weight factor ba zai warware bambance-bambancen sha, metabolism, hanyar bayarwa, yawan fallasa ko tsawon rayuwar fallasa ba. Zai samar da adadin da aka canza kawai, ba hujjar aminci ba.

Gwajin gavage na shekaru biyu da ɗan gajeren magani na intravenous ƙarƙashin kulawar likita suna tambayar abubuwa daban-daban. Wannan bambanci yana hana yin extrapolation na lamba kai tsaye; ba ya soke sakamakon dabbobi. Kimantawa mai amfani tana farawa ne da ainihin compound da formulation, adadi, hanya, yawan bayarwa, tsawon lokaci da dalilin amfani. “'Yan digo kaɗan” ba ya bayyana concentration ko ƙarar da aka auna.

Idan an bayar da methylene blue saboda dalilin likita, sakamakon ƙari kaɗai ba zai iya tantance ko amfanin wannan maganin ya fi haɗarinsa ba. Idan ana la'akari da maimaita amfani na zaɓi, bai kamata a bayyana haɗarin cutar daji na dogon lokaci da ba a auna ba a matsayin sifili. Abubuwan da suka fi gaggawa, ciki har da hulɗar magunguna da yiwuwar haemolysis, an tattauna su a illolin gefe da abubuwan da ba su dace da amfani ba.

Don ƙarin karatu, yi amfani da laburaren bincike don bambance nazarin mutane da gwaje-gwajen dabbobi da ƙwayoyin halitta. Muhimmin tambaya ga kowace takarda ita ce irin fallasar da ta gwada da kuma ainihin sakamakon da ta auna.