Hormesis na shuɗin methylene: bayani kan lankwasan amsa ga kashi

An ba wani bera 4 milligrams per kilogram na shuɗin methylene bayan ya koyi gane wani abu, kuma washegari ya tuna da shi. An ba wani beran kuma 50, amma da ƙyar yake juya ƙafafun gudunsa. Ƙwayar sinadarin ɗaya ce. Amma alkiblar tasirinta ba ɗaya ba ce. Duk wanda ya karanta fiye da 'yan takardun bincike kan shuɗin methylene ya taɓa ganin wannan juyawar tasiri, kuma tana da suna: hormesis, wato amsa mai matakai biyu inda ƙaramin matakin fuskantar sinadari da babba ke tura ma'aunin sakamako ɗaya zuwa alkiblu masu saɓani.

Sunan yana da amfani ne kawai idan ka san abin da yake nunawa da abin da ba ya nunawa. Wannan maƙala ta yi bayani kan rukunin bayanai huɗu da aka wallafa game da shuɗin methylene, kowannensu yana da nasa ma'aunin sakamako, zangon matakin taro da tsarin gwaji, kuma ta nuna dalilin da halayen sinadaran rinin ke sa irin waɗannan juyawar tasiri su zama masu yiwuwa. Ta ƙare da gargaɗin da bayanan ke jaddadawa: lankwasa da ya kai kololuwa a wani gwaji bayani ne na wannan gwajin, ba hanyar zaɓar kashin mutum ba.

Wannan tsari yana da suna, kuma ma'anar sunan ta fi yadda yake sauti takamaimai

Southam da Ehrlich ne suka ƙirƙiri kalmar hormesis a 1943, sannan Calabrese da Baldwin suka ba ta ma'anarta ta zamani ta ƙididdiga: amsa ta daidaitawa mai matakai biyu, wadda ke faruwa kai tsaye ko ta hanyar rama canji bayan an dagula daidaiton cikin jiki. Ka lura da abin da babu a cikin wannan ma'anar. Kalmar mai amfani ba ta bayyana ba. Hormesis tana cewa lankwasan ya sauya alkibla ne kawai, ba wani abu fiye da haka ba.

Siffar da kake gani ta dogara da ma'aunin sakamakon da ke kan ginshiƙin tsaye. Idan ma'aunin aikin kirki ne kamar aikin enzyme, amfani da oxygen ko makin ƙwaƙwalwa, ƙarin aiki a ƙaramin kashi da raguwar aiki a babban kashi na zana U mai juye. Idan ma'aunin wani abu ne mara kyau, kamar yawan faruwar cuta, ragewa a ƙaramin kashi da ƙaruwa a babban kashi na zana J ko U. Alaƙar ɗaya ce, abin da aka auna a ginshiƙin tsaye ne ya bambanta. Yawancin binciken shuɗin methylene na auna ayyuka masu kyau, don haka wannan maƙala tana amfani da lankwasai masu siffar U mai juye, tare da fahimtar cewa harafin da ake amfani da shi zaɓin yadda ake zana bayanan ne.

Bitar 2008 da ta tattara amsoshin hormesis na shuɗin methylene ta fayyace girman tasirin. A halayya, ilimin ayyukan jiki da kimiyyar sinadaran halittu, amsoshin da ke cikin yankin ƙara aiki sun kai kusan 130 zuwa 160 percent na rukunin kwatance, da matsakaici kusa da 140, kafin su koma matakin rukunin kwatance sannan su faɗi ƙasa da shi yayin da kashi ke ci gaba da ƙaruwa. Wannan zango taƙaitaccen bayanin gwaje-gwaje da yawa ne, ba wata sifa ta ƙwayar sinadarin ba. Kowane lankwasa da ke ƙasa yana da nasa kololuwa cikin nasa raka'o'in awo.

Dalilin da wannan ƙwayar sinadari musamman za ta iya juya tasiri

Shuɗin methylene ba mai bayar da electron kawai ba ne. Mai jigilar electron ne da zai iya komawa yanayinsa na baya. Shuɗin nau'insa da ya yi oxidation yana karɓar electrons, ya koma nau'in da ya yi reduction marar launi, sannan wannan nau'in na iya miƙa electrons ɗin zuwa matakai na gaba. An bayyana wannan jigilar electron da ke bayan lankwasan a bayanin yadda shuɗin methylene ke motsa electrons, kuma wannan jigilar ita ce tushen batun nan.

A ƙananan matakan taro, wannan zagayawa tana ba numfashin ƙwayoyin halitta wata madadin hanya. Rinin da ya yi reduction na iya yin oxidation a cytochrome oxidase, enzyme na ƙarshe a sarƙar jigilar electron, yana ƙara saurin aikinsa tare da amfani da oxygen da ƙarfin numfashin ƙwayoyin halitta. A matakan taro mafi girma, wannan halin sinadarin na neman electron yana fara gogayya da sarƙar da aka saba maimakon taimaka mata: yana karkatar da electrons daga hanyarsu ta yau da kullum, yana cinye oxygen kai tsaye, yana kuma samar da nau'o'in oxygen masu saurin amsawa maimakon makamashi mai amfani. Ƙaramin mai jigila mai hanzarta amsar sinadarai, ƙarin gudana; wurin karɓar electrons mai yawa da ke gogayya, raguwar gudana. Halayen sinadarin sun sa sauyin alkibla ya zama mai yiwuwa, amma ba su tabbatar da inda wani takamaiman ma'aunin sakamako zai kai kololuwa ba.

Shaida mai zaman kanta ta dogaro da matakin taro ta fito daga ƙwayoyin halitta da ba su da mitochondria ko kaɗan. A cikin gwaje-gwajen erythrocyte na 1976, ƙaramin matakin taro na 1 micromolar ya ƙara aikin hanyar hexose monophosphate ta hanyar da ta dogara ƙwarai da oxyhemoglobin, yayin da matakin taro mai girma sau ɗari, na 0.1 millimolar, bai dogara sosai da kasancewar oxyhemoglobin ba, kuma ya samar da hydrogen peroxide a duk hanyoyin gwajin guda uku da aka yi amfani da su. Rinin ɗaya ne, hanyoyin aiki biyu ne, matakin taro ne ya raba su. Jajayen ƙwayoyin jini ba sa yin numfashin ƙwayoyin halitta, don haka wannan ba lankwasan mitochondria ba ne, amma yana nuna yadda halayen oxidation da reduction na rinin ke sauyawa yayin da matakin taro ke ƙaruwa, wanda shi ne ainihin abin da bayanin mitochondria ke buƙata.

Lankwasai huɗu, tsarin gwaji huɗu

Hoton da ke ƙasa ya sake zana rukunin bayanai huɗun gefe da gefe. Kowane sashe yana riƙe da nasa ginshiƙan awo da yanayin gwaji, domin ɗora su a ma'auni ɗaya zai zama ƙaryar farko da wannan maƙala za ta faɗa. Zanen na bayani ne kawai; ainihin ƙimomi da yanayin gwaji suna cikin rubutun.

Sashe A: cytochrome oxidase a niƙaƙƙen ƙwaƙwalwar bera. Lankwasan mitochondria mafi tsabta ya zo ta wata majiya ta biyu, an zana shi a cikin bitar daga bayanan niƙaƙƙen ƙwaƙwalwar bera: kusan 138 percent na aikin rukunin kwatance a 0.5 micromolar, ya koma matakin rukunin kwatance kusa da 5 micromolar, ya faɗi ƙasa da matakin farko kusa da 10 micromolar, inda marubutan suka nuna cewa mai yiwuwa rinin yana karɓe electrons daga haɗaɗɗun sinadaran da sarƙar ke amfani da su kullum. Niƙaƙƙen nama, micromolar, gwajin auna sha haske. Wannan jumlar ita ce dukkan mahallin, kuma lankwasan ba ya da ma'ana a wajensa.

Sashe B: ƙwaƙwalwar bera da gudu a ƙafafun gudu. A cikin binciken ƙwaƙwalwar bera, an gwada tasirin allura ɗaya bayan horo bayan sa'o'i 24. Kashi na 1 zuwa 10 milligrams per kilogram bai sa motsi da cin abinci su bambanta da na rukunin ruwan gishiri ba, yayin da 50 zuwa 100 milligrams per kilogram ya rage gudu a ƙafafun gudu sosai (ƙimar tsakiya ta juyawa 35 idan aka kwatanta da 279), kuma kashi mafi girma ya haifar da miƙewar gashin jiki, motsi marar daidaituwa da mutuwa ɗaya. Kashi na 4 milligram per kilogram ya inganta sabawa da gane abu: berayen da aka ba sinadarin sun ɗauki kusan ƙarin daƙiƙu 10 suna duba sabon abin. Amfani da oxygen a ƙwaƙwalwa ya ƙaru a niƙaƙƙen nama da aka sa wa rinin da ya yi reduction a ƙananan matakan micromolar da kuma a ƙwaƙwalwar da aka ɗauka sa'o'i 24 bayan an ba dabbobin 1 milligram per kilogram a jikinsu. Ka lura da rarrabewar: gwajin halayya ya yi amfani da kashi da aka ba dabbobi bayan horo domin ya shiga jiki gaba ɗaya, gwajin amfani da oxygen kuma ya yi amfani da matakan taro a niƙaƙƙen nama tare da kashi ɗaya a dabba mai rai; gwaje-gwaje biyu ne, ba lankwasa ɗaya ba.

Sashe C: zebrafish a hanyar gwajin T. Binciken zebrafish ya tsoma kifayen da aka horar cikin ruwan sinadari na sa'o'i 12 bayan horo, a matakan taro da aka ƙayyade na 0.1, 0.5, 5.0 ko 10.0 micromolar, tare da rukunin kwatance mai shuɗin rinin abinci. Rukunin 0.5 micromolar ya fi yin kyau, rukunin 5.0 ya yi daidai da rukunin kwatance, rukunin 10.0 kuma ya yi ƙasa da rukunonin ƙananan kashi. Akwai abubuwa biyu da ya kamata a yi taka-tsantsan da su game da wannan sashe. Micromolar na ruwan gwaji ba micromolar na jini ko ƙwaƙwalwa ba ne; rarrabuwar sinadarin da taruwarsa suna shiga tsakanin ruwan tanki da naman jiki. Kuma ƙarfin shaidar ƙididdiga ya yi ƙasa da yadda siffar lankwasan ke nunawa: babban kashi ya bambanta da rukunonin ƙananan kashi, amma ba a bayar da rahoton wasu bambance-bambancen rukuni masu muhimmanci a ƙididdiga ba. Lankwasan na gaske ne amma bai da cikakken daidaito.

Sashe D: hanyar madadin metabolism a erythrocyte. Metz da abokan aikinsa sun kwatanta 1 micromolar da 0.1 millimolar a jajayen ƙwayoyin jinin ɗan Adam ƙarƙashin iska, carbon monoxide, da cakuda da ta sa kusan duk hemoglobin ya zama carboxyhemoglobin a matsin oxygen irin na jiki. Ƙarin aiki a ƙaramin kashi ya rushe ba tare da oxyhemoglobin ba; ƙarin aiki a babban kashi kuwa da ƙyar ya nuna bambanci. Peroxide ya bayyana ne kawai a babban kashi. Wannan sashe ya dace ya kasance tare da sauran a matsayin bayanin kimiyyar sinadarai, ba a matsayin batu na huɗu a wani babban lankwasa guda ba: babu mitochondria, tazarar matakin taro sau ɗari, cakudun iskar gas da aka sarrafa.

Dalilin da kololuwar ba su dace da juna ba, kuma bai kamata su dace ba

Kololuwar huɗun suna a 0.5 micromolar a niƙaƙƙen nama, 4 milligrams per kilogram da aka yi allurarsa bayan horo, 0.5 micromolar a ruwan tanki, da kwatancen ƙarami da babban matakin taro masu tazarar sau ɗari a jajayen ƙwayoyin jini. Ɗaukar kowanne biyu a matsayin lamba ɗaya kuskuren haɗa abubuwa masu bambancin nau'i ne. Kowane ma'aunin sakamako yana da nasa lankwasa: matakin da ya fi dacewa da ƙwaƙwalwa ba lallai ya yi daidai da wanda ya fi dacewa da aikin oxidase, amfani da oxygen, motsi ko samar da peroxide ba. Kowace raka'ar matakin taro tana nufin wani abu dabam: micromolar na niƙaƙƙen nama, micromolar da aka ƙayyade na ruwan gwaji, milligrams per kilogram da aka ba jiki gaba ɗaya, da matakan taro a plasma, ƙwaƙwalwa da mitochondria ma'aunai ne daban-daban, kuma halin shuɗin methylene na taruwa a mitochondria da ƙwaƙwalwa yana ƙara bambanta su. Kowane samfurin gwaji yana ƙara nasa yadda jiki ke ɗauka, rarrabawa, sauyawa da fitar da sinadarin: nau'in dabba, hanyar bayarwa da lokacin bayarwa suna ƙayyade wane nama zai haɗu da nawa na rinin da kuma tsawon lokacin haɗuwar.

A nan ne kuma muhimmancin kashi da hanyar bayarwa ga tsaron shuɗin methylene yake bayyana, domin tasirin manyan kashi a waɗannan takardun bincike—rage motsi, motsi marar daidaituwa, bera ɗaya da ya mutu, samar da peroxide—alamun guba ne a cikin nasu tsarin gwaji, ba iyakokin aminci ga wani dabam ba. Duk wanda ke son mayar da 4 milligrams per kilogram a bera zuwa tsarin amfani ga ɗan Adam ya kamata ya fara karanta yadda sakamakon binciken dabbobi yake da alaƙa da shaidar ɗan Adam: sauƙaƙƙen sauya milligram-per-kilogram tsakanin nau'o'in halittu bai isa ba.

Kuskuren da ya kamata a guje masa

U mai juye yana jan hankali domin yana kama da na'urar daidaita kashi da aka yi wa alamar wurin da ya fi dacewa. Ba haka yake ba. Hormesis tana bayyana abin da ya faru ga ma'aunin sakamako ɗaya a tsarin gwaji ɗaya. Idan ka haɗa irin waɗannan bayanai huɗu, za ka sami kololuwa huɗu a tsarin raka'o'i huɗu, wanda shi ne akasin na'urar daidaita kashi. Amfani da waɗannan lankwasai cikin gaskiya shi ne na kwatance da taka-tsantsan: ka yi tsammanin tasiri zai juya da matakin taro, ka yi tsammanin kowane ma'aunin sakamako zai juya a nasa matsayi, kuma kada ka amince da duk wata magana da ta aro kololuwar wani gwaji don tabbatar da wani kashi a nau'in halitta, hanyar bayarwa, naman jiki ko manufar amfani dabam. Bambanci tsakanin tsarin da aka gani a gwaji da shawarar kashin da mutum zai ɗauka shi ne ainihin manufar wannan maƙala gaba ɗaya; an sake faɗinsa don kada a rasa shi.

Yadda za a karanta takardar bincike ta gaba kan amsa ga kashi

Tambayoyi huɗu sun dace da kusan kowane lankwasan shuɗin methylene da za ka gani. Wane ma'aunin sakamako ne yake kan ginshiƙin tsaye, kuma juyawarsa za ta zana U ko J. Wane matakin taro ne ginshiƙin kwance yake nunawa a zahiri: na ruwan gwaji da aka ƙayyade, niƙaƙƙen nama, plasma, ƙwaƙwalwa da aka kiyasta, ko kashin da aka ba jiki gaba ɗaya. Wane samfurin gwaji da lokaci ne suka samar da shi: niƙaƙƙen nama, ƙwayoyin halitta da aka shuka tare da fitilu a kunne ko a kashe, dabbobin da aka horar aka ba su kashi kafin ko bayan horo, kuma yaushe aka gwada su. Kuma mene ne rukunin kwatance: ruwan gishiri, shuɗin rinin abinci, ruwan ɗaukar sinadarin, da kuma ko ƙididdigar takardar tana goyon bayan kowace magana ta kwatanta rukuni biyu ko siffar gaba ɗaya kawai. Takardar da ta amsa duk huɗun ta cancanci lokacinka. Wadda ta bayar da rahoton kololuwa ba tare da su ba ta ba ka lamba ba tare da adireshi ba.