Hormesis ya methylene blue: gusobanukirwa imirongo y'ingano n'igisubizo

Imbeba imwe ihabwa 4 milligrams per kilogram za methylene blue nyuma yo kwiga kumenya ikintu, maze ku munsi ukurikiyeho ikacyibuka. Indi mbeba ihabwa 50, maze igahindukiza uruziga yirukiraho gake cyane. Molekile ni imwe. Icyerekezo cy'ingaruka si kimwe. Umuntu wese wasomye inyandiko z'ubushakashatsi kuri methylene blue zitari nke yahuye n'iri hinduka, kandi rifite izina: hormesis, igisubizo gifite ibyiciro bibiri aho guhura n'ingano nto n'inini bituma ikintu kimwe gipimwa gihinduka mu byerekezo bihabanye.

Iryo zina rifite akamaro gusa iyo uzi icyo risobanura n'icyo ridasobanura. Iyi nyandiko isesengura amatsinda ane y'amakuru y'ubushakashatsi kuri methylene blue yatangajwe, buri tsinda rifite ikintu cyaryo gipimwa, intera y'ubucucike n'imiterere y'igerageza, ikerekana n'impamvu imiterere y'iki kinyabutabire gitanga ibara ituma ayo mahinduka ashoboka. Isoza n'umuburo ayo makuru asaba ko witabwaho: umurongo ugera ku mpinga mu igerageza rimwe usobanura ibyabaye muri iryo gerageza, ntabwo ari uburyo bwo guhitamo ingano umuntu ku giti cye akwiriye gukoresha.

Iyi miterere ifite izina, kandi icyo iryo zina risobanura ni gito kurusha uko ryumvikana

Ijambo hormesis ryahimbwe mu 1943 na Southam na Ehrlich, maze Calabrese na Baldwin bariha igisobanuro cyaryo cya none gishingiye ku bipimo: igisubizo cyo kwihuza n'impinduka gifite ibyiciro bibiri, kibaho mu buryo butaziguye cyangwa binyuze mu kwishyura ihungabana ry'uburinganire bw'imbere mu mubiri. Reba ikibura muri icyo gisobanuro. Ijambo ingirakamaro ntiririmo. Hormesis ivuga ko umurongo uhindura icyerekezo, nta kindi.

Imiterere ubona iterwa n'ikintu gipimwa gishyizwe ku murongo uhagaze w'igishushanyo. Iyo gipimwa ari imikorere myiza, nk'imikorere ya anzime, ikoreshwa rya ogisijeni cyangwa amanota yo kwibuka, kwiyongera guterwa n'ingano nto gukurikiwe no kugabanuka guterwa n'ingano nini bishushanya U icuramye. Iyo gipimwa ari ikintu kibi, nk'inshuro indwara iboneka, kugabanuka guterwa n'ingano nto gukurikiwe no kwiyongera guterwa n'ingano nini bishushanya J cyangwa U. Isano ni imwe, ariko igipimwa ku murongo uhagaze kiratandukanye. Ubushakashatsi bwinshi kuri methylene blue bupima imikorere myiza, ni yo mpamvu iyi nyandiko ivuga imirongo ya U icuramye, hakumvikana ko inyuguti ikoreshwa iterwa n'uburyo bwo gushushanya amakuru.

Inyandiko y'isuzuma yo mu 2008 yakusanyije ibisubizo bya hormesis ya methylene blue igaragaza neza urugero rw'izo mpinduka. Mu myitwarire, imikorere y'umubiri n'ubutabire bw'ibinyabuzima, ibisubizo biri mu gice cyongera imikorere bigera hafi kuri 130 kugeza kuri 160 ku ijana by'ibipimo byo kugereranya, impuzandengo ikaba hafi ya 140, mbere yo kongera kumanuka bikanyura ku gipimo cyo kugereranya hanyuma bikajya munsi yacyo uko ingano ikomeza kwiyongera. Iyo ntera ni incamake y'amagerageza menshi, ntabwo ari umwihariko wa molekile. Buri murongo ukurikira ufite impinga yawo mu bipimo byawo.

Impamvu iyi molekile by'umwihariko ishobora guhindura icyerekezo

Methylene blue ntabwo ari ikinyabutabire gitanga elegitoroni gusa. Ni ikizitwara gisubira mu miterere yacyo. Imiterere yayo y'ubururu yatakaje elegitoroni yakira elegitoroni, igahinduka imiterere idafite ibara yungutse elegitoroni, kandi iyo miterere ishobora guhererekanya izo elegitoroni ikazigeza ku bikurikiraho. Ihererekanya rya elegitoroni riri inyuma y'iyi mirongo risobanurwa mu nkuru y'uko methylene blue yimura elegitoroni, kandi hano icyo gikorwa cyo kuzitwara ni cyo shingiro ry'ibisobanuro byose.

Ku bucucike buke, iyo mihindagurikire iha uguhumeka kw'uturemangingo indi nzira. Iki kinyabutabire gitanga ibara cyungutse elegitoroni gishobora kuzitakaza kuri cytochrome oxidase, anzime yo ku musozo w'uruhererekane rutwara elegitoroni, bityo kikongera umuvuduko w'imikorere yayo hamwe n'ikoreshwa rya ogisijeni n'ubushobozi bwo guhumeka kw'uturemangingo. Ku bucucike bwinshi, uwo mwihariko wo gushaka elegitoroni utangira guhatana n'uruhererekane rusanzwe aho kurufasha: kuyobya elegitoroni zikava mu nzira yazo isanzwe, gukoresha ogisijeni mu buryo butaziguye no kubyara ibinyabutabire bya ogisijeni byitabira cyane aho gutanga ingufu z'ingirakamaro. Iyo ikizitwara gifasha imikoranire y'ubutabire kiri gike, urujya n'uruza ruriyongera; iyo hari igitwara elegitoroni gikabije kandi gihatanira na zo, ruragabanuka. Ubutabire butuma ihinduka ry'icyerekezo rishoboka, nubwo butemeza aho ikintu runaka gipimwa kizagera ku mpinga.

Ibindi bimenyetso byigenga by'uko ingaruka ziterwa n'ubucucike biva mu turemangingo tutagira mitokondiriya na mba. Mu magerageza yo mu 1976 ku turemangingo dutukura tw'amaraso, ubucucike buke bwa 1 micromolar bwongereye imikorere y'inzira ya hexose monophosphate binyuze mu buryo bwari bushingiye cyane kuri oxyhemoglobin, naho ubucucike bwa 0.1 millimolar, bwikubye inshuro ijana, ntibwagaragaje kwishingikiriza cyane ku kuba oxyhemoglobin ihari kandi bwabyaye hydrogen peroxide yagaragajwe n'uburyo bwose butatu bwo gupima bwakoreshejwe. Ikinyabutabire gitanga ibara ni kimwe, uburyo bw'imikorere ni bubiri, butandukanyijwe n'ubucucike. Uturemangingo dutukura tw'amaraso ntidushobora guhumeka, bityo uyu si umurongo wa mitokondiriya, ariko werekana ko ubutabire bwo kwakira no gutanga elegitoroni bw'iki kinyabutabire buhindura imiterere uko ubucucike bwiyongera, ari na byo ibisobanuro bishingiye kuri mitokondiriya bisaba.

Imirongo ine, imiterere ine y'igerageza

Igishushanyo gikurikira cyongera gushushanya amatsinda ane y'amakuru, kimwe iruhande rw'ikindi. Buri gice kigumana imirongo yacyo y'ibipimo n'imiterere y'igerageza, kuko kubishyira byose ku rugero rumwe byaba ari cyo kinyoma cya mbere iyi nyandiko ishobora kuvuga. Igishushanyo cyerekana imiterere rusange; imibare nyayo n'imiterere y'igerageza biri mu nyandiko.

Igice A: cytochrome oxidase mu ruvange rw'ubwonko bw'imbeba bwasewe. Umurongo wa mitokondiriya ugaragara neza kurusha indi tubona si amakuru yatanzwe bwa mbere muri iyo nyandiko; washushanyijwe mu nyandiko y'isuzuma hakoreshejwe amakuru y'uruvange rw'ubwonko bw'imbeba bwasewe: hafi ya 138 ku ijana by'imikorere y'igipimo cyo kugereranya kuri 0.5 micromolar, gusubira ku gipimo cyo kugereranya hafi ya 5 micromolar, no kujya munsi y'igipimo fatizo hafi ya 10 micromolar, aho abanditsi bavuga ko bishoboka ko iki kinyabutabire gitanga ibara kivana elegitoroni ku matsinda ya poroteyine asanzwe y'uruhererekane. Uruvange rw'ingirangingo zasewe, micromolar, igipimo gikoresha ubwinshi bw'urumuri runyura mu kintu. Iyo nteruro ni yo mimerere yose y'igerageza, kandi uwo murongo nta cyo usobanura hanze yayo.

Igice B: kwibuka kw'imbeba no kwiruka ku ruziga. Mu bushakashatsi ku kwibuka kw'imbeba, imbeba zatewe rimwe nyuma yo kwigishwa, zipimwa nyuma y'amasaha 24. Ingano za 1 kugeza kuri 10 milligrams per kilogram zatumye kugenda no kurya bitagaragaza itandukaniro n'iby'izahawe amazi arimo umunyu, naho 50 kugeza kuri 100 milligrams per kilogram zagabanyije cyane kwiruka ku ruziga (agaciro ko hagati ka 35 ugereranyije na 279 by'ukuzenguruka), kandi ingano nini kurusha izindi yatumye ubwoya buhagarara, kugenda bitajyana neza, ndetse hapfa imbeba imwe. Ingano ya 4 milligrams per kilogram yateje imbere kumenyera no kumenya ibintu: imbeba zahawe umuti zamaze hafi amasegonda 10 arenga ku kintu gishya. Ikoreshwa rya ogisijeni mu bwonko ryiyongereye haba mu ruvange rw'ubwonko bwasewe rwahuye n'iki kinyabutabire gitanga ibara cyungutse elegitoroni ku bucucike buke bwa micromolar, no mu bwonko bwafashwe nyuma y'amasaha 24 inyamaswa nzima ihawe 1 milligram per kilogram. Zirikana itandukaniro: imyitwarire yapimwe hakoreshejwe ingano zahawe umubiri wose nyuma yo kwigishwa, ikoreshwa rya ogisijeni ripimwa hakoreshejwe ubucucike bwo mu ruvange rw'ingirangingo zasewe hamwe n'ingano imwe yahawe inyamaswa nzima; ayo ni amagerageza abiri, ntabwo ari umurongo umwe.

Igice C: zebrafish mu nzira zimeze nka T. Ubushakashatsi kuri zebrafish bwibije amafi yari yarigishijwe mu mazi arimo umuti mu gihe cy'amasaha 12 nyuma yo kwigishwa, ku bucucike bwagenwe bwa 0.1, 0.5, 5.0 cyangwa 10.0 micromolar, bugereranywa n'itsinda ryari mu mazi arimo ibara ry'ubururu rikoreshwa mu biribwa. Itsinda rya 0.5 micromolar ryitwaye neza kurusha ayandi, irya 5.0 ringana n'itsinda rigereranywa, naho irya 10.0 ryitwara nabi kurusha amatsinda yahawe ingano nto. Iki gice kigendana n'ibintu bibiri byo kwitondera. Micromolar yo mu mazi bibizwamo si micromolar yo mu maraso cyangwa mu bwonko; ikwirakwira n'ukwirundanya bibaho hagati y'amazi yo mu kigega n'ingirangingo. Kandi ibimenyetso by'ibarurishamibare bifite imbaraga nke kurusha uko imiterere y'umurongo ibigaragaza: ingano nini yari itandukanye n'amatsinda yahawe ingano nto, nta rindi tandukaniro rifite agaciro mu ibarurishamibare hagati y'amatsinda ryatangajwe. Umurongo urahari, ariko ntusobanutse neza.

Igice D: inzira yo mu turemangingo dutukura tw'amaraso. Metz na bagenzi be bagereranyije 1 micromolar na 0.1 millimolar mu turemangingo dutukura tw'amaraso y'abantu, mu mwuka, muri carbon monoxide, no mu ruvange rwatumaga hemoglobine hafi ya yose iba carboxyhemoglobin ku muvuduko wa ogisijeni usanzwe mu mubiri. Kwiyongera kw'imikorere ku ngano nto kwaragabanutse cyane igihe oxyhemoglobin yaburaga; kwiyongera ku ngano nini ntikwagize impinduka nini. Peroxide yagaragaye ku ngano nini gusa. Iki gice kigomba kujyana n'ibindi nk'icyerekana ubutabire, ntabwo ari nk'akadomo ka kane ku murongo umwe uhuriweho: nta mitokondiriya, ubucucike butandukanyijwe n'inshuro ijana, imvange za gazi zahinduwe mu igerageza.

Impamvu impinga zitangana, kandi zitagomba kungana

Impinga enye ziri kuri 0.5 micromolar mu ruvange rw'ingirangingo zasewe, 4 milligrams per kilogram zatewe nyuma yo kwigishwa, 0.5 micromolar mu mazi yo mu kigega, no ku bipimo bibiri, kimwe gito n'ikindi kinini, bitandukanyijwe n'inshuro ijana mu turemangingo dutukura tw'amaraso. Gufata bibiri ibyo ari byo byose nk'umubare umwe ni ikosa ryo kuvanga ibyiciro bitandukanye. Buri kintu gipimwa gifite umurongo wacyo: igipimo cyiza kurusha ibindi cyo kwibuka si ngombwa ko gihura n'icy'imikorere ya oxidase, ikoreshwa rya ogisijeni, kugenda cyangwa ikorwa rya peroxide. Buri gipimo cy'ubucucike gisobanura ikintu gitandukanye: micromolar yo mu ruvange rw'ingirangingo zasewe, micromolar yagenwe mu mazi bibizwamo, milligrams per kilogram zahawe umubiri wose, n'ubucucike bwo mu gice cy'amazi cy'amaraso, mu bwonko no muri mitokondiriya ni ibipimo bitandukanye, kandi kuba methylene blue ikunda kwirundanya muri mitokondiriya no mu bwonko bituma bikomeza gutandukana. Buri buryo bw'igerageza bwongeraho umwihariko wabwo w'uko umuti ukwirakwira kandi ugatunganywa mu mubiri: ubwoko bw'ikinyabuzima, inzira yo kuwutanga n'igihe utangirwa bigena ingirangingo zihura n'iki kinyabutabire gitanga ibara, ingano zihura na yo n'igihe bimara.

Aha ni na ho uruhare rw'ingano n'inzira yo gutanga methylene blue mu mutekano wayo rugira akamaro, kuko ingaruka z'ingano nini ziri muri izi nyandiko — kugabanuka kw'imikorere yo kugenda, kugenda bitajyana neza, imbeba imwe yapfuye, ikorwa rya peroxide — ari ibimenyetso by'uburozi mu miterere y'amagerageza yazo, ntabwo ari imipaka y'umutekano ku bandi. Kandi umuntu wese wumva ashaka guhindura 4 milligrams per kilogram mu mbeba gahunda yo guha umuntu umuti akwiriye kubanza gusoma uko ibyabonetse mu nyamaswa bifitanye isano n'ibimenyetso byo mu bantu: guhindura gusa milligram-per-kilogram hagati y'ubwoko bw'ibinyabuzima ntibihagije.

Ikosa ryo kwirinda

U icuramye irashukana kuko isa n'igikoresho cyo kugena ingano kiriho ikimenyetso cy'ahantu heza kurusha ahandi. Si cyo. Hormesis isobanura ibyabaye ku kintu kimwe gipimwa mu miterere imwe y'igerageza. Shyira hamwe ibisobanuro bine nk'ibyo, ubone impinga enye mu buryo bune bw'ibipimo, ari na byo bitandukanye cyane n'igikoresho cyo kugena ingano. Gukoresha iyi mirongo mu buryo bw'ukuri ni ukuyigereranya no kuyikuramo umuburo: tegereza ko ingaruka zishobora guhindura icyerekezo bitewe n'ubucucike, tegereza ko buri kintu gipimwa gihindura icyerekezo ku gipimo cyacyo, kandi ntukizere ikivugwa icyo ari cyo cyose gifata impinga y'igerageza rimwe kikayishingiraho cyemeza ingano yo gukoresha mu bundi bwoko bw'ikinyabuzima, mu yindi nzira, mu zindi ngirangingo cyangwa ku yindi ntego. Itandukaniro hagati y'imiterere igaragara mu magerageza n'ibyemezo by'ingano umuntu ku giti cye akoresha ni yo ngingo y'iyi nyandiko yose, yongeye kuvugwa kugira ngo itirengagizwa.

Uko wasoma inyandiko ikurikira ku ngano n'igisubizo

Ibibazo bine bihuye hafi na buri murongo wa methylene blue uzahura na wo. Ni iki gipimwa kiri ku murongo uhagaze, kandi guhindura icyerekezo kwacyo byashushanya U cyangwa J? Ni ubuhe bucucike umurongo utambitse werekana koko: ubwateganyijwe mu mazi bibizwamo, ubwo mu ruvange rw'ingirangingo zasewe, ubwo mu gice cy'amazi cy'amaraso, ubwagereranyijwe mu bwonko cyangwa ingano yahawe umubiri wose? Ni ubuhe buryo bw'igerageza n'ibihe byawubyaye: uruvange rw'ingirangingo zasewe, uturemangingo dukurishwa mu igerageza amatara yaka cyangwa azimye, inyamaswa zigishijwe zahawe umuti mbere cyangwa nyuma yo kwigishwa, kandi zapimwe ryari? Kandi ni iki cyakoreshejwe mu kugereranya: amazi arimo umunyu, ibara ry'ubururu rikoreshwa mu biribwa, ikinyabutabire gitwarirwamo umuti; ese ibarurishamibare ry'inyandiko rishyigikira buri kivugwa ku kugereranya amatsinda abiri abiri, cyangwa rishyigikira imiterere rusange gusa? Inyandiko isubiza ibyo bine byose ikwiriye umwanya wawe. Ivuga impinga itabisobanuye iba yaguhaye umubare utazi aho ubarizwa.