Isebenza njani i-methylene blue: ukudluliselwa kwee-electron, nalapho ziphelela khona

Iflaski evaliweyo esebhentshini yeyona ndlela imfutshane nenyanisekileyo yokuchaza indlela i-methylene blue esebenza ngayo. Amanzi, i-glucose, intwana ye-sodium hydroxide, kunye nedayi eyaneleyo ukwenza ulwelo lube luhlaza okwesibhakabhaka olunzulu nolungenakuphazanywa. Linda imizuzu embalwa, umbala oluhlaza okwesibhakabhaka uyanyamalala de iflaski ibonakale ngathi inamanzi nje. Yishukumise, umbala ubuye kwangoko. Emva koko uyaphela kwakhona, kwaye iya kuqhubeka isenza oko logama kusekho i-glucose ekulungeleyo ukunika ii-electron kunye ne-oxygen ekulungeleyo ukuzamkela.

Akukho nto itshintshileyo ngedayi ngaphandle kwenani lee-electron ezithweleyo. Xa i-oxidised, iluhlaza okwesibhakabhaka. Xa i-reduced, ayinjalo. Phantse yonke enye into ekuncwadi lwezonyango nolophando malunga nale molekyuli isuka kweli nyathelo linye libuyiselwayo, kuba imolekyuli enokuthatha ii-electron komnye umlingane ize izinike omnye sisidluliseli, kwaye isidluliseli asenzi nto ngokwaso. Into esiyenzayo ixhomekeke ngokupheleleyo koko kumi kwicala ngalinye laso.

Iifom ezimbini, nokuba kutheni esi sibini sibalulekile

Ifom ye-oxidised yinkqubo yamaringi athe tyaba, enentlawulo entle. Olo lwakhiwo luthe tyaba nolunentlawulo seso sizathu sokuba ibekane ecaleni kwee-nucleic acids, ibophe kwizakhiwo ezine-sialylation kwiimembrane zeeseli, kwaye ifunxe ngamandla ukukhanya okubonakalayo phakathi malunga ne-600 kunye ne-700 nanometres, eyinxalenye ye-spectrum iliso lomntu eliyibona njengohlaza okwesibhakabhaka.

Ifom ye-reduced yahlukile. Ayinantlawulo, inyibilika emafutheni kunasemanzini, kwaye ayinambala. I-ionisation yayo iphantsi kakhulu kwi-pH engaphakathi emzimbeni, malunga neepesenti ezimbalwa. Ngoko imolekyuli ye-reduced iwela lula imembrane yeseli nge-diffusion, kwaye xa sele ingaphakathi, apho imeko ine-oxidising ngakumbi, inokuphinda ibe yi-oxidised ize ibanjiswe ngempumelelo. Inkqubo yamaringi ye-oxidised ithe tyaba; eye-reduced inokujijeka. Ezo ziphumo zolwakhiwo, kunye notshintsho lombala ngokwalo, ziyinxalenye yebali lezi fom zimbini ngokwazo, kwaye zichazwa ngokweenkcukacha ngakumbi kuthelekiso lwe-methylene blue kunye ne-leucomethylene blue.

Ukwamkela ii-electron

Idayi ye-oxidised iya kwamkela ii-electron kubanikeli abaninzi abahlukeneyo. I-glucose ekwiflaski yomboniso ngomnye wabo. Ngaphakathi kweseli, ii-pyridine nucleotides ze-reduced kunye namacandelo ekhonkco lokuthuthwa kwee-electron le-mitochondria ngabanye. Xa i-methylene blue isenziwa i-reduced kwithishu ene-oxygen, umjikelo ewumisayo usebenzisa zombini iarhente ye-reducing kunye ne-oxygen, kwaye uvelisa reactive oxygen species, ikakhulu i-hydrogen peroxide. Idayi iphuma kumjikelo ingatshintshanga, ilungele ukuwuqhuba kwakhona.

Eli nqaku lokugqibela lichaza ukuphikisana okunokubonakala ngathi kukungakhathali. I-methylene blue ichazwa kuncwadi njengazo zombini i-pro-oxidant kunye ne-antioxidant, kwaye zombini ezi nkcazo zinokuxhaswa. Inokunciphisa ukuveliswa kwe-superoxide ngokusebenza njengomamkeli we-electron owenziweyo, ijikise ukuhamba kwee-electron kude neendawo zee-enzyme apho i-oxygen ibiya kuguqulwa ibe zii-superoxide radicals. Kwiinkcubeko zeeseli zesibindi iboniswe ukuba ivuselela ii-enzyme zokhuselo lwe-antioxidant zesigaba se-2, kuquka i-thioredoxin reductase 1 kunye ne-NADPH quinone oxidoreductase. Ukuba leliphi kula macala mabini olibonayo kuxhomekeke ekubeni leliphi icala lesidluliseli eliswele ii-electron ngaloo mzuzu. Umbuzo ofana nokuthi "ingaba i-methylene blue yi-antioxidant" awubunjwanga kakuhle de uchaze ukuba yeyiphi inkqubo, kowuphi umxube, kwaye yintoni enye ekhoyo.

Ukudlulisela ii-electron phambili

Xa idayi sele ibambe i-electron eyongezelelweyo, zinokwenzeka izinto ezintathu ezahluke kakhulu, kwaye zidla ngokuchazwa phantsi kwesihloko esinye. Akufanele kube njalo.

Inokudlulisela i-electron kwiziko lesinyithi. Owona mzekelo ucacileyo yi-haemoglobin ethe yaguqulwa nge-oxidation ukusuka kwimeko ye-ferrous ukuya kweye-ferric. Kule meko ayinakuthwala i-oxygen. Kwiiseli ezibomvu, i-enzyme yenza idayi ibe yi-reduced, emva koko idayi ye-reduced idlulisele ii-electron kwi-oxidised haem iron ngaphandle kwe-enzyme, ibuyisele i-haemoglobin esebenzayo ize ibuyisele idayi kwifom yayo ye-oxidised. Idayi ayipheli ngenxa yoku; ijikeleza. Umfanekiso wezonyango osekelwe kule reaction sisihloko sesibhedlele, kwaye ingcaciso ye-methylene blue kwi-methemoglobinemia ichaza indlela esetyenziswa ngayo nokuba kutheni ijongwa ngokusondeleyo kangaka.

Inqaku elinyanisekileyo malunga nokufundwa kwemithombo: ezi review zimbini eli nqaku lisekelwe kuzo azibizi i-reducing cofactor efanayo kwinyathelo le-enzyme, enye ithi NADH enye ithi NADPH. Ukungavisisani kuyinyani kwaye akukasonjululwa kwimithombo ekhoyo apha, ngoko inkcazo ekhuselekileyo kukuchaza indima edlalwa yinxalenye nganye endaweni yokunika igama le-cofactor elinye.

Inokudlulisela amandla, okanye i-electron, kwi-oxygen, ukuba kukho ukukhanya. Le ndlela ikhona kuphela phantsi kokukhanya. Idayi evuselelweyo ifikelela kwimeko ye-triplet, kwaye ukusuka apho zinokwenzeka iindlela ezimbini. Kweyokuqala, idayi evuselelweyo isebenzisana ngokuthe ngqo nemolekyuli ekufutshane, ithathe i-hydrogen okanye idlulisele i-electron, nto leyo evelisa ii-radicals; ukusabela namanzi ngale ndlela kuvelisa ii-hydroxyl radicals. Kweyesibini, amandla okuvuselelwa adluliselwa kwi-oxygen ngokwayo, evelisa singlet oxygen, uhlobo olune-electrophilic kakhulu olutshabalala ngaphakathi kwee-microseconds kwaye olwamkelwa ngokubanzi njengeyona ndlela iphambili i-methylene blue ekhanyiselweyo eyonakalisa ngayo iiseli ze-microbial. Iireaction kunye nee-lipid ne-peptide ze-cell envelope, kunye neziseko ze-guanine kwi-DNA, ziphakathi kweziphumo ezibhalwe phantsi.

Isiphumo esisebenzayo sale ndlela kukuba ukukhanyiselwa kutshintsha amanani ngee-orders of magnitude. Kwidatha eqokelelwe nguWainwright noCrossley, i-methylene blue ngokuchasene ne-Pseudomonas aeruginosa inomxube omncinci obulala iintsholongwane malunga ne-500 micromolar ebumnyameni, kunye malunga ne-25 micromolar phantsi kwedosi yokukhanya ye-12 joules per square centimetre. Ngokuchasene nohlobo olunye lwe-Staphylococcus aureus, amaxabiso asebumnyameni nawakhanyiselweyo omabini yi-5 micromolar. Ngamanye amazwi, ukuba imolekyuli ithathwa njenge-antimicrobial kwaphela asiyonto exhomekeke kwimolekyuli yodwa; yipropathi yemolekyuli kunye nokukhanya.

Inokusebenza ngokuthe ngqo kwindawo ye-enzyme, ngaphandle kwesidluliseli. I-methylene blue yenza i-oxidation ye-ferrous iron ebotshelelwe kwi-nitric oxide synthase, nto leyo eyenza i-enzyme ingasebenzi. Ivimba i-soluble guanylate cyclase, kwaye phakathi kwe-1 kunye ne-10 micromolar ngowona mxube welebhu oqhelekileyo osetyenziselwa loo njongo. Ithintela i-monoamine oxidase type A nge-IC50 phakathi kwe-27 kunye ne-180 nanomolar, eyindlela esekelwe kuyo interaction ebhalwe kakuhle kunye nee-serotonin reuptake inhibitors nesizathu sokuba ii-drug interactions ze-methylene blue zibe ludidi lwazo ngokwazo.

Ezi ndlela zintathu zahlukile ngokwekhemistri. Ukuzidibanisa zibe yibango elinye lokuba i-methylene blue isebenza nge-redox cycling sesona sizathu siphambili sokuba okubhaliweyo okuninzi ngayo kuvakale kuqinisekile kodwa kungacacanga ngaxeshanye.

Iiyantlukwano ezine ezimisela ukuba ingxelo yendlela yokusebenza ithetha nto na

Yeyiphi ifom. Idayi ye-reduced ayinakutshintshwa ngokungathi iyafana nedayi ye-oxidised. Ukuthintelwa kwe-acetylcholinesterase kubonisa umgibe: ngexesha elide le-in vitro incubation, i-methylene blue yenziwa i-reduced ngokuthe ngcembe iye kwifom yayo engenambala, kwaye ukuthintelwa kuyehla, kuba imolekyuli ye-reduced ayiyithinteli loo enzyme. Uvavanyo oluqhutywa ixesha elide ngokwaneleyo ukutshintsha ifom luya kunika ingxelo yesiphumo esibuthathaka kwaye lubangele ingcaciso engachanekanga.

Ngowuphi umxube. Uluhlu lwelebhu lokuthintela i-soluble guanylate cyclase yi-1 ukuya kwi-10 micromolar. Ukuphelisa i-glutamate-mediated transmission kwiziqwenga ze-rat hippocampus kwafuna i-5 ukuya kwi-50 micromolar. Iziphumo eziyityhefu kwinkcubeko yeeseli zichazwa ngaphezulu kwe-100 micromolar. Ezi ayizizo iimvavanyo ezifanayo, kwaye indlela eqinisekiswe kwi-50 micromolar ayifumaneki ngokuzenzekelayo kumguli onomxube weplasma oyinxalenye nje yaloo nto.

Yeyiphi indlela. I-absolute oral bioavailability imalunga ne-72 per cent, kwaye i-terminal plasma half-life yi-5 ukuya kwi-7 hours. Ukulawulwa ngomlomo kuvelisa imixube ephezulu emathunjini nakwisibindi; ukulawulwa nge-intravenous kuvelisa imixube ephezulu ebuchotsheni. Indlela yokulawulwa imisela ukuba yeyiphi ithishu edibana nee-electron.

Yeyiphi imodeli, nokuba izibane zazivuliwe na. Uninzi loncwadi lweendlela zokusebenza lusekelwe kwinkcubeko yeeseli nakuphando lweempuku, kwaye iziphumo ze-in vitro kule molekyuli zixhomekeke ekuchanabekeni ekukhanyeni, kwi-membrane potential nakwimeko ye-redox yeeseli, kuba isibane semicroscope sanele ukuyenza i-photosensitise. Phakathi kwe-65 kunye ne-85 per cent yedosi elawulwayo yenziwa i-reduced ibe yifom engenambala kwiiseli ezibomvu nakwithishu ye-peripheral. Nganye kwezo variables imi phakathi kwendlela ecacileyo kwisitya sovavanyo kunye nebango malunga nomntu.

Kutheni umbuzo wobunyulu ungumbuzo wekhemistri

Ukukhanyiselwa kwenza i-demethylation ye-methylene blue. Imveliso yokuqala yi-Azure B, emva koko yi-Azure A, emva koko yi-thionin, kwaye amandla aphezulu okukhanya avelisa ukonakala okungakumbi kunamandla asezantsi. Imolekyuli eluncedo lwayo lusekwe ekukwazini ukwamkela nokunikela ii-electron, ke ngoko, yimolekyuli enemveliso yokonakala ekulindeleke ukuba ibe zizalamane zekhemistri ezisondeleyo ezihlala kwisisombululo esifanayo. Ukubunjwa koko kusekhonteyina ayisosicukuthwane nje.

Yiyo loo nto ukuthobela inkcazo ye-USP kuvavanyo olunentsingiselo kumthengi. Imveliso engayifezekisiyo yidayi, kwaye idayi ithwala ukungcola, kuquka Azure B, heavy metals kunye residual solvents, izinto umntu oziginyayo angazifuniyo. Omnye umgibe ngumthengisi ovavanya kuphela heavy metals aze abonise isiphumo njengokuthobela ngokupheleleyo. Blupreme ibambisene nomenzi wamayeza we-methylene blue kwaye ivavanya inkcazo epheleleyo: identity, purity, organic impurities, residual solvents, elemental impurities, residue on ignition, microbial limits kunye bacterial endotoxins. Uxwebhu lovavanyo lwelabhoratri oluxhasa ibhetshi nganye luyapapashwa, kwaye ukukhetha umthengisi ikakhulu kungumbandela wokujonga ukuba olo xwebhu lukhona na nokuba luquka ntoni.

Isibini esinye esibuyiselwayo. Iindlela ezininzi eziphuma kuso. Indlela yiyo emisela ukuba ibango lingathini. :::