Methylene blue nehormesis: nei makombama emhedzisiro zvichienderana nedosi achigona kuchinja kwaakananga

Rimwe gonzo rinopiwa 4 milligrams per kilogram yemethylene blue pashure pekudzidza kuziva chinhu, uye mangwana acho rinorangarira. Rimwe gonzo rinopiwa 50, uye rinototadza kutenderedza vhiri raro rekumhanya. Morekuru racho rakafanana. Kwakananga mhedzisiro yacho hakuna kufanana. Chero munhu akaverenga mapepa akati wandei pamusoro pemethylene blue akambosangana nekupinduka uku, uye kune zita: hormesis, mhinduro ine zvikamu zviviri umo kuiswa pachinhu pamwero wakaderera nepamusoro kunosundira mhedzisiro imwe chete inoyerwa kumativi akapesana.

Zita iri rinobatsira chete kana uchiziva zvarinovimbisa nezvarisingavimbisi. Chinyorwa chino chinoongorora maseti mana edata remethylene blue rakabudiswa, rimwe nerimwe riine mhedzisiro yaro inoyerwa, huwandu hwaro hweconcentration uye marongerwo aro ekuedza, chichiratidza kuti nei kemisitiri yedhayi iri ichiita kuti kupinduka kwakadai kuve kunonzwisisika. Chinopedzisa neyambiro inosimbiswa nedata: kombama rinosvika pakakwirira mune kumwe kuedza rinotsanangura kuedza ikoko, harisi nzira yekusarudza dosi remunhu.

Maitiro aya ane zita, uye zvarinoreva zvishoma pane zvarinoita serinoreva

Zita rekuti hormesis rakagadzirwa muna 1943 naSoutham naEhrlich, ndokuzopiwa tsananguro yaro yemazuva ano ine zviyero naCalabrese naBaldwin: mhinduro yekuchinjira kumamiriro ezvinhu ine zvikamu zviviri, inobuda zvakananga kana kuburikidza nekugadzirisa kunoitika kana kuenzana kwemamiriro emukati memuviri kwavhiringidzwa. Cherechedza chisipo mutsananguro iyoyo. Shoko rekuti zvinobatsira harina kutaurwa. Hormesis inongoti kombama rinochinja kwarakananga, hapana chimwe.

Chimiro chaunoona chinoenderana nemhedzisiro inoyerwa iri paakisi yakatwasuka. Kana mhedzisiro yacho iri kushanda kunobatsira, kwakadai sekushanda kweenzayimu, kushandiswa kweokisijeni kana chiyero chendangariro, kukurudzirwa nedosi diki kuchiteverwa nekudzivirirwa nedosi guru kunodhirowa U yakapidiguka. Kana mhedzisiro yacho iri chinhu chakaipa, chakadai sehuwandu hwevanobatwa nechirwere, kuderedzwa nedosi diki kuchiteverwa nekuwedzerwa nedosi guru kunodhirowa J kana U. Ukama hwacho humwe chete, chinoyerwa paakisi yakatwasuka ndicho chakasiyana. Tsvakurudzo zhinji dzemethylene blue dzinoyera mabasa anobatsira, saka chinyorwa chino chinotaura nezvemakombama eU yakapidiguka, zvichinzwisiswa kuti vara rearufabheti racho rinobva pakusarudzwa kwemadhirowerwo egirafu.

Ongororo ya2008 yakaunganidza mhinduro dzemethylene blue dzine hormesis inoratidza ukuru hwacho zvakajeka. Pamaitiro emhuka, kushanda kwemuviri nekemisitiri yezvipenyu, mhinduro dziri munzvimbo yekukurudzirwa dzinosvika paanenge 130 kusvika 160 percent yechiyero chekuenzanisa, avhareji iri pedyo ne140, dzisati dzadzika dzichipfuura chiyero chekuenzanisa dzobva dzava pasi pacho dosi parinoramba richikwira. Huwandu ihwohwo ipfupiso yekuedza kwakawanda, kwete hunhu husingachinji hwemorekuru racho. Kombama rimwe nerimwe riri pasi apa rine pakakwirira paro muzviyero zvaro.

Nei morekuru iri richigona kupindura mhedzisiro

Methylene blue haisi chinhu chinongopa maerekitironi. Mutakuri unogona kufamba uchidzoka nekudzokorora. Chimiro chayo chebhuruu chakaitwa oxidation chinogamuchira maerekitironi, chichiva chimiro chakaitwa reduction chisina ruvara, uye chimiro ichocho chinogona kupfuudza maerekitironi acho kumatanho anotevera. Kupfuudzana kwemaerekitironi kunokonzera makombama aya kunotsanangurwa munyaya yekuti methylene blue inofambisa sei maerekitironi, uye basa remutakuri uyu ndiro musimboti wenyaya iri pano.

Paconcentration dzakaderera, kutenderera uku kunopa kufema kwemasero imwe nzira. Dhayi yakaitwa reduction inogona kuitwa oxidation pacytochrome oxidase, enzayimu yekupedzisira muketani inotakura maerekitironi, ichiwedzera kumhanya kwekushanda kwayo pamwe nekushandiswa kweokisijeni nekugona kufema kwemasero. Paconcentration dzakakwirira, kemisitiri imwe chete iyi inokwezva maerekitironi inotanga kukwikwidzana neketani yakajairika pane kuibatsira: ichitsausa maerekitironi panzira yaanowanzotevera, ichishandisa okisijeni zvakananga, uye ichigadzira mhando dzeokisijeni dzinopinda nyore mukuita kwekemisitiri pane kugadzira simba rinobatsira. Mutakuri mudiki unobatsira kuita kwekemisitiri, kuyerera kwakawanda; chinokweva maerekitironi chakawandisa chichikwikwidza, kuyerera kushoma. Kemisitiri yacho inoita kuti kuchinja kwekwakananga mhedzisiro kunzwisisike, asi haivimbisi kuti mhedzisiro ipi neipi inoyerwa ichasvika pakakwirira papi.

Humwe uchapupu hwakazvimirira hwekuti concentration ine basa hunobva mumasero asina mitochondria zvachose. Mukuedza kwemaerythrocyte kwa1976, concentration yakaderera ye1 micromolar yakakurudzira nzira yehexose monophosphate kuburikidza nemaitiro ainyanya kutsamira paoxyhemoglobin, nepo concentration yakakwirira kazana ye0.1 millimolar yakanga isinganyanyi kutsamira pakuvapo kweoxyhemoglobin uye yakagadzira hydrogen peroxide, sezvakaratidzwa nenzira dzose nhatu dzekuyera dzakashandiswa. Dhayi imwe chete, maitiro maviri, akapatsanurwa neconcentration. Masero matsvuku eropa haakwanisi kufema nenzira yemitochondria, saka iri harisi kombama remitochondria, asi rinoratidza kemisitiri yeoxidation nereduction yedhayi ichichinja hunhu concentration painokwira, zvinova ndizvo chaizvo zvinodiwa netsananguro yemitochondria.

Makombama mana, marongerwo mana ekuedza

Mufananidzo uri pasi apa unodhirowazve maseti mana edata ari padivi nepadivi. Chikamu chimwe nechimwe chinochengeta maakisi acho nemamiriro acho, nokuti kuaisa pamwe chete pachiyero chimwe chete kwaizova kunyepa kwekutanga kwechinyorwa chino. Mufananidzo wacho unongoratidza maitiro acho; zviyero chaizvo nemamiriro acho zviri murugwaro.

Chikamu A: cytochrome oxidase mumusanganiswa wehuropi hwegonzo hwakapwanywa. Kombama remitochondria rakajeka kupfuura mamwe rinobva mudata rakatorwa kune imwe tsvakurudzo, rakadhirowewa muongororo kubva kudata remusanganiswa wehuropi hwemakonzo hwakapwanywa: kushanda kunenge kuri pa138 percent yechiyero chekuenzanisa pa0.5 micromolar, kuchidzokera pachiyero chekuenzanisa pedyo ne5 micromolar, uye kuchidzika pasi pechiyero chekutanga pedyo ne10 micromolar, apo vanyori vanofungidzira kuti dhayi iri kutora maerekitironi ichiabvisa pazvikamu zvakajairika zveketani. Musanganiswa wezvinyama zvakapwanywa, micromolar, kuyera nekutorwa kwechiedza. Mutsara iwoyo ndiwo mamiriro ose ekuedza, uye kombama racho harina zvarinoreva kunze kwawo.

Chikamu B: ndangariro dzemakonzo nekumhanya pavhiri. Mutsvakurudzo yendangariro dzemakonzo, majekiseni akapiwa kamwe chete pashure pekudzidziswa akaongororwa pashure pe24 hours. Madosi e1 kusvika 10 milligrams per kilogram akasiya kufamba nekudya zvisina mutsauko nezvakaonekwa pamakonzo akapiwa mvura ine munyu, nepo 50 kusvika 100 milligrams per kilogram akaderedza kumhanya pavhiri zvakanyanya (kukosha kwepakati kwaiva 35 zvichienzaniswa ne279 kutenderera) uye dosi repamusoro-soro rakaita kuti mvere dzimire, kufamba kusarongeka uye gonzo rimwe rife. Dosi re4 milligram per kilogram rakavandudza kujairira uye kuziva zvinhu: makonzo akapiwa dhayi akapedza nguva inenge 10 seconds yakawanda pachinhu chitsva. Kushandiswa kweokisijeni muuropi kwakakwira mumusanganiswa wezvinyama zvakapwanywa wakaiswa dhayi yakaitwa reduction ine concentration yakaderera yakayerwa nemicromolar, uyewo muuropi hwakatorwa pashure pe24 hours gonzo benyu rapiwa 1 milligram per kilogram. Cherechedza kupatsanurwa uku: maitiro emakonzo akaongororwa pachishandiswa madosi aiparadzirwa mumuviri wose pashure pekudzidziswa, kushandiswa kweokisijeni kwakaongororwa pachishandiswa concentration dzemusanganiswa wezvinyama zvakapwanywa pamwe nedosi rimwe chete rakapiwa mhuka iri mhenyu, uye uku kuedza kuviri, kwete kombama rimwe chete.

Chikamu C: zebrafish munzira dzinovhiringidza dzakaita saT. Mutsvakurudzo yezebrafish, hove dzakanga dzadzidziswa dzakanyikwa kwe12 hours pashure pekudzidziswa muconcentration dzakatarwa dzemvura yekunyikira dze0.1, 0.5, 5.0 kana 10.0 micromolar, dzichienzaniswa neboka rakaiswa mudhayi yechikafu yebhuruu. Boka re0.5 micromolar rakaita zvakanaka kupfuura ose, boka re5.0 rakafanana neboka rekuenzanisa, uye boka re10.0 rakaita zvakaipa kupfuura mapoka emadosi akaderera. Chikamu ichi chine yambiro mbiri. Micromolar yemvura yekunyikira haisi micromolar yeropa kana yehuropi; kupararira nekuungana kwedhayi zvinopinda pakati pemvura yemutangi nezvinyama. Uye uchapupu hwezviverengero hahuna kusimba sezvinoita sechimiro chegirafu chinoratidza: dosi guru rakasiyana nemapoka emadosi akaderera, asi hapana mimwe misiyano yakakosha maererano nezviverengero yakataurwa pakati pemapoka. Kombama racho nderechokwadi asi harina kunyatsotsanangurika.

Chikamu D: nzira yehexose monophosphate mumaerythrocyte. Metz nevamwe vake vakaenzanisa 1 micromolar ne0.1 millimolar mumasero matsvuku eropa evanhu ari mumhepo, mucarbon monoxide, uye mumusanganiswa waiita kuti hemoglobin inenge yose ive carboxyhemoglobin pakudzvinyirira kweokisijeni kwakajairika mumuviri. Kukurudzirwa nedosi diki kwakaderera zvakanyanya pasina oxyhemoglobin; kukurudzirwa nedosi guru hakuna kunyanya kuchinja. Peroxide yakaonekwa padosi guru chete. Chikamu ichi chinofanira kuva padivi pezvimwe sechiratidzo chekemisitiri, kwete sepfungwa yechina pakombama rimwe guru rinomiririra zvose: hapana mitochondria, musiyano weconcentration wakapetwa kazana, uye misanganiswa yemagasi yakachinjwa.

Nei panosvika makombama pakakwirira pasingawirirani, uye pasingafaniri kuwirirana

Nzvimbo ina dzepamusoro dziri pa0.5 micromolar mumusanganiswa wezvinyama zvakapwanywa, pa4 milligrams per kilogram yakabaiwa pashure pekudzidziswa, pa0.5 micromolar mumvura yemutangi, uye pakuenzanisa mwero wakaderera newakakwirira zvakasiyana kazana mumasero matsvuku eropa. Kutora chero zviviri sezvinomiririra nhamba imwe chete kukanganisa kunosanganisa zvinhu zvemarudzi akasiyana. Mhedzisiro imwe neimwe inoyerwa ine kombama rayo: mwero wakanakira ndangariro haufaniri kufanana newakanakira kushanda kweoxidase, kushandiswa kweokisijeni, kufamba kana kugadzirwa kweperoxide. Chiyero chimwe nechimwe checoncentration chinoreva chinhu chakasiyana: micromolar yemusanganiswa wezvinyama zvakapwanywa, micromolar yakatarwa mumvura yekunyikira, milligrams per kilogram inopiwa muviri wose, uye concentration dzemvura yeropa, dzehuropi nedzemitochondria zviyero zvakasiyana, uye tsika yemethylene blue yekuungana mumitochondria nemuuropi inoita kuti zvirambe zvakasiyana. Mhando imwe neimwe inoshandiswa mukuedza inowedzera maitiro ayo ekutorwa, kuparadzirwa nekubviswa kwechinhu mumuviri: rudzi rwemhuka, nzira yekupiwa uye nguva zvinotara kuti zvinyama zvipi zvinosangana nedhayi yakawanda sei uye kwenguva yakareba sei.

Apa ndipo panokoshawo basa redosi nenzira yekupiwa mukuchengeteka kwemethylene blue, nokuti mhedzisiro yemadosi makuru mumapepa aya—kudzvinyirirwa kwekufamba, kufamba kusarongeka, gonzo rimwe rakafa, kugadzirwa kweperoxide—zviratidzo zvehuturu mumamiriro avo ekuedza, kwete miganhu yekuchengeteka yemumwe munhu. Uye munhu anoedzwa kushandura 4 milligrams per kilogram mugonzo kuita chirongwa chekupiwa munhu anofanira kutanga averenga kuti zvakawanikwa mumhuka zvinobatana sei neuchapupu hwevanhu: kungoshandura milligram-per-kilogram pakati pemarudzi akasiyana hakukwani.

Kukanganisa kunofanira kudziviswa

U yakapidiguka inokwezva nokuti inoita sebhatani rekugadzirisa dosi rine nzvimbo yakanakisisa yakamaka. Haisi iro. Hormesis inotsanangura zvakaitika kumhedzisiro imwe chete inoyerwa mumarongerwo mamwe chete ekuedza. Unganidza tsananguro ina dzakadai uye unowana nzvimbo ina dzepamusoro mumasisitimu mana ezviyero, zvinova zvakasiyana chose nebhatani rekugadzirisa. Kushandiswa kwemakombama aya nenzira yakatendeseka ndekwekuenzanisa uye kunyevera: tarisira kuti mhedzisiro inogona kupinduka concentration painochinja, tarisira kuti mhedzisiro imwe neimwe inoyerwa ipinduke panzvimbo yayo, uye usavimba nechero chirevo chinokwereta nzvimbo yepamusoro yekumwe kuedza kuti chitsigire dosi mune rumwe rudzi, neimwe nzira yekupiwa, mune zvimwe zvinyama kana nechinangwa chakasiyana. Musiyano pakati pemaitiro anoonekwa pakuedza nezvisarudzo zvemadosi emunhu ndiwo musimboti wechinyorwa chino chose, wataurwazve kuti usapotswe.

Maverengero epapepa rinotevera remhedzisiro zvichienderana nedosi

Mibvunzo mina inokodzera anenge makombama ose emethylene blue auchasangana nawo. Ndeipi mhedzisiro inoyerwa iri paakisi yakatwasuka, uye kupinduka kwayo kungadhirowa U kana J here. Ndeipi concentration inonyatsoratidzwa neakisi yakachinjika: yakatarwa mumvura yekunyikira, yemusanganiswa wezvinyama zvakapwanywa, yemvura yeropa, inofungidzirwa yehuropi, kana dosi rakapiwa muviri wose. Ndeipi mhando nemarongerwo enguva zvakaburitsa mhedzisiro yacho: musanganiswa wezvinyama zvakapwanywa, masero akarimwa pachiedza kana murima, mhuka dzakadzidziswa dzikapiwa dosi dzisati dzadzidziswa kana pashure pekudzidziswa, dzikaongororwa riini. Uye chii chakashandiswa kuenzanisa: mvura ine munyu, dhayi yechikafu yebhuruu, chinhu chinotakurira dhayi, uye kuti zviverengero zvepapepa zvinotsigira here chirevo chimwe nechimwe chekuenzanisa mapoka maviri kana kungotsigira chimiro chose. Pepa rinopindura yose mina rakakodzera nguva yako. Rinongotaura nzvimbo yepamusoro pasina izvozvo rinenge rakupa nhamba isina kero.