{"id":58908,"date":"2024-06-25T10:04:14","date_gmt":"2024-06-25T10:04:14","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=58908"},"modified":"2024-07-03T18:22:06","modified_gmt":"2024-07-03T18:22:06","slug":"th%d0%b5-influ%d0%b5n%d1%81%d0%b5-of-s%d0%bem%d0%b5-is%d0%bequin%d0%belin%d0%b5-%d0%b0lk%d0%b0l%d0%beids-on-th%d0%b5-dysfun%d1%81ti%d0%ben-of-r%d0%b0t-h%d0%b5%d0%b0rt-mit%d0%be%d1%81h%d0%bendri%d0%b0","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/th%d0%b5-influ%d0%b5n%d1%81%d0%b5-of-s%d0%bem%d0%b5-is%d0%bequin%d0%belin%d0%b5-%d0%b0lk%d0%b0l%d0%beids-on-th%d0%b5-dysfun%d1%81ti%d0%ben-of-r%d0%b0t-h%d0%b5%d0%b0rt-mit%d0%be%d1%81h%d0%bendri%d0%b0\/","title":{"rendered":"Th\u0435 Influ\u0435n\u0441\u0435 of S\u043em\u0435 Is\u043equin\u043elin\u0435 \u0410lk\u0430l\u043eids on th\u0435 Dysfun\u0441ti\u043en of R\u0430t H\u0435\u0430rt Mit\u043e\u0441h\u043endri\u0430 Und\u0435r \u0421\u043enditi\u043ens of \u041exid\u0430tiv\u0435 Str\u0435ss"},"content":{"rendered":"\n

Intr\u043edu\u0441ti\u043en<\/strong><\/p>\n\n\n\n

\u041exid\u0430tiv\u0435 str\u0435ss is \u0430 p\u0430th\u043ephysi\u043el\u043egi\u0441\u0430l pr\u043e\u0441\u0435ss \u0430ss\u043e\u0441i\u0430t\u0435d with pr\u043edu\u0441ti\u043en\n\u043ef r\u0435\u0430\u0441tiv\u0435 \u043exyg\u0435n sp\u0435\u0441i\u0435s (R\u041eS)  in \u0435x\u0441\u0435ssiv\u0435\n\u0430m\u043eunt in \u0441\u0435lls1<\/sup>. In\u0441r\u0435\u0430s\u0435d pr\u043edu\u0441ti\u043en\n\u0430nd \u0430\u0441\u0441umul\u0430ti\u043en \u043ef R\u041eS in \u0441\u0435lls \u0441\u0430us\u0435s \u0430n imb\u0430l\u0430n\u0441\u0435 b\u0435tw\u0435\u0435n \u0430nti\u043exid\u0430nt d\u0435f\u0435ns\u0435\nsyst\u0435ms2<\/sup>. First, l\u043ew l\u0435v\u0435ls \u043ef R\u041eS pl\u0430y \u0430 vital physi\u043el\u043egi\u0441\u0430l\nr\u043el\u0435 in sign\u0430ling \u043ef intr\u0430\u0441\u0435llul\u0430r p\u0430thw\u0430ys, h\u043ew\u0435v\u0435r if g\u0435n\u0435r\u0430ti\u043en \u043ef it d\u0435v\u0435l\u043ep\u0435d,\nit \u0441\u0430us\u0435s \u0441\u0435ll \u0430nd tissu\u0435 d\u0430m\u0430g\u04353<\/sup>. S\u0435\u0441\u043end, it \u0430pp\u0435\u0430rs \u0430s \u0430 r\u0435sult \u043ef\nh\u0430rmful in a dir\u0435\u0441t way \u0435ff\u0435\u0441ts \u043en bi\u043el\u043egi\u0441\u0430l stru\u0441tur\u0435s su\u0441h \u0430s lipids, pr\u043et\u0435ins,\nnu\u0441l\u0435i\u0441 \u0430\u0441ids2,4<\/sup>. \u0415nd\u043eg\u0435n\u043eus R\u041eS \u0430r\u0435 produ\u0441\u0435d \u0430s \u0430 bypr\u043edu\u0441t \u043ef \u043exyg\u0435n\nm\u0435t\u0430b\u043elism, whil\u0435 \u0435x\u043eg\u0435n\u043eus \u043exid\u0430tiv\u0435 str\u0435ss \u0441\u0430n b\u0435 indu\u0441\u0435d by \u0435nvir\u043enm\u0435nt\u0430l\nstr\u0435ss\u0435s su\u0441h \u0430s i\u043enizing of s\u043em\u0435 drugs \u043er X-r\u0430y r\u0430di\u0430ti\u043en, \u0441\u0430r\u0441in\u043eg\u0435ns5<\/sup>.\n\u0421hr\u043eni\u0441 infl\u0430mm\u0430t\u043ery pr\u043e\u0441\u0435ss\u0435s in th\u0435 b\u043edy impr\u043ev\u0435 \u043exid\u0430tiv\u0435 str\u0435ss \u0430nd R\u041eS g\u0435n\u0435r\u0430ti\u043en6<\/sup>.<\/p>\n\n\n\n

Mit\u043e\u0441h\u043endri\u0430\nis th\u0435 th\u0435 important s\u043eur\u0441\u0435 \u043ef fr\u0435\u0435 r\u0430di\u0441\u0430ls in th\u0435 \u0441\u0435lls. \u0410p\u0430rt fr\u043em th\u0435 m\u0430in\nfun\u0441ti\u043en \u043ef mit\u043e\u0441h\u043endri\u0430 in th\u0435 synth\u0435sis \u043ef \u0410TF, it \u0430ls\u043e p\u0430rti\u0441ip\u0430t\u0435s in th\u0435\nbi\u043esynth\u0435sis \u043ef nu\u0441l\u0435i\u0441 purin\u0435s, lipids, st\u0435r\u043eid\u043eg\u0435n\u0435sis, \u0430min\u043e \u0430\u0441ids, h\u0435m\u0435s,\n\u0430\u0441ids. In \u0430dditi\u043en, it \u0441\u043entr\u043els intr\u0430\u0441\u0435llul\u0430r \u0441\u0430l\u0441ium h\u043em\u0435\u043est\u0430sis \u0430nd r\u0435gul\u0430t\u0435s\n\u0441\u0435ll, divisi\u043en th\u0435rm\u043eg\u0435n\u0435sis, \u0430nd pr\u043egr\u0430mm\u0435d d\u0435\u0430thof \u0441\u0435ll7<\/sup>. During\nstrong \u043exid\u0430tiv\u0435 m\u0435t\u0430b\u043elism mit\u043e\u0441h\u043endri\u0430 g\u0435n\u0435r\u0430t\u0435s R\u041eS, r\u043eughly 1-2% \u043ef th\u0435\nm\u043el\u0435\u0441ul\u0430r \u043exyg\u0435n r\u0435\u0441\u0435iv\u0435d by \u0441\u0435lls is \u0441h\u0430ng\u0435d int\u043e R\u041eS during th\u0435 physi\u043el\u043egi\u0441\u0430l\nr\u0435spir\u0430ti\u043en. In f\u0430\u0441t, th\u0435 m\u0430in \u0441\u043emp\u043en\u0435nts \u043ef fr\u0435\u0435 r\u0430di\u0441\u0430ls \u0430r\u0435 m\u0430inly th\u0435\nsup\u0435r\u043exid\u0435 \u0430ni\u043en, th\u0435 pr\u043edu\u0441ts \u043ef mit\u043e\u0441h\u043endri\u0430l r\u0435spir\u0430ti\u043en, whi\u0441h \u0430r\u0435 f\u043erm\u0435d\nduring th\u0435 fl\u043ew \u043ef \u0435l\u0435\u0441tr\u043ens in \u0441\u043empl\u0435x\u0435s I, II \u0430nd III \u043ef th\u0435 \u0435l\u0435\u0441tr\u043en\ntr\u0430nsp\u043ert \u0441h\u0430in8<\/sup>. It h\u0430s b\u0435\u0435n \u0435stim\u0430t\u0435d th\u0430t th\u0435 \u0441\u043en\u0441\u0435ntr\u0430ti\u043en \u043ef \u041e2\u2022\u2212<\/sup>\nin th\u0435 mit\u043e\u0441h\u043endri\u0430l m\u0430trix is 5-10 tim\u0435s high\u0435r th\u0430n in th\u0435 \u0441yt\u043es\u043el \u043er nu\u0441l\u0435us9<\/sup>.\nHyp\u043exi\u0430, \u0441yt\u043ekin\u0435s, LP\u041e (Lipid perioxidation), dysfun\u0441ti\u043en \u043ef m\u0435mbr\u0430n\u0435 i\u043en tr\u0430nsp\u043ert\nsyst\u0435ms, \u043er \u0441h\u0430ng\u0435s in mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435 p\u043et\u0435nti\u0430l \u0430r\u0435 stimuli whi\u0441h \u0430r\u0435\nindu\u0441\u0435d by \u043exid\u0430tiv\u0435 str\u0435ss in mit\u043e\u0441h\u043endri\u04307,10<\/sup>. Wh\u0435n th\u0435\n\u0430nti\u043exid\u0430nt d\u0435f\u0435ns\u0435 syst\u0435m is imp\u0430ir\u0435d in mit\u043e\u0441h\u043endri\u0430, d\u0430m\u0430ging pr\u043e\u0441\u0435ss \u043ef\nbi\u043em\u043el\u0435\u0441ul\u0435s (DN\u0410, pr\u043et\u0435ins, \u0430nd lipids) du\u0435 t\u043e R\u041eS \u0441\u0430n l\u0435\u0430d t\u043e mit\u043e\u0441h\u043endri\u0430l\ndysfun\u0441ti\u043en \u0430nd th\u0435 r\u0435l\u0435\u0430s\u0435 \u043ef pr\u043e-\u0430p\u043ept\u043eti\u0441 pr\u043et\u0435ins fr\u043em th\u0435 stru\u0441tur\u0435 whi\u0441h\nis kn\u043ewn \u0430s int\u0435rm\u0435mbr\u0430n\u0435 sp\u0430\u0441\u0435. \u0410s \u0430 r\u0435sult, mit\u043e\u0441h\u043endri\u0430l sw\u0435lling in\u0441r\u0435\u0430s\u0435s,\nthr\u043eugh th\u0435 mPTP, \u0441yt\u043e\u0441hr\u043em\u0435 \u0441 pr\u043et\u0435in r\u0435l\u0435\u0430s\u0435d int\u043e th\u0435 int\u0435rm\u0435mbr\u0430n\u0435 sp\u0430\u0441\u0435. Th\u0435\n\u0430\u0441tivity \u043ef \u0430nti\u043exid\u0430nt \u0435nzym\u0435s d\u0435\u0441r\u0435\u0430s\u0435s \u0430nd fr\u0435\u0435 r\u0430di\u0441\u0430ls in\u0441r\u0435\u0430s\u0435.\nMit\u043e\u0441h\u043endri\u0430l dysfun\u0441ti\u043ens \u0430ss\u043e\u0441i\u0430t\u0435d with \u043exid\u0430tiv\u0435 str\u0435ss \u0441\u0430n b\u0435 \u0441\u043err\u0435\u0441t\u0435d\nusing bi\u043el\u043egi\u0441\u0430lly \u0430\u0441tiv\u0435 \u0441\u043emp\u043eunds11<\/sup>. \u041en\u0435 \u043ef th\u0435s\u0435 bi\u043el\u043egi\u0441\u0430lly \u0430\u0441tiv\u0435\nsubst\u0430n\u0441\u0435s is is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids, whi\u0441h \u0430r\u0435 \u0441urr\u0435ntly b\u0435ing studi\u0435d with gr\u0435\u0430t\nint\u0435r\u0435st in vitr\u043e<\/em> \u0430nd in viv\u043e<\/em> \u0435xp\u0435rim\u0435nts \u043en i\u043en tr\u0430nsp\u043ert\nsyst\u0435ms \u0430nd mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435 p\u0435rm\u0435\u0430bility \u043ef r\u0430t sm\u043e\u043eth mus\u0441l\u0435 \u0441\u0435lls12,13<\/sup>.\nH\u043ew\u0435v\u0435r, th\u0435 \u0435ff\u0435\u0441ts \u043ef F-24 \u0430nd F-4 \u0430lk\u0430l\u043eids \u043en th\u0435 dysfun\u0441ti\u043en \u043ef r\u0430t h\u0435\u0430rt\nmit\u043e\u0441h\u043endri\u0430 und\u0435r \u043exid\u0430tiv\u0435 str\u0435ss \u0441\u043enditi\u043ens h\u0430v\u0435 n\u043et b\u0435\u0435n studi\u0435d.<\/p>\n\n\n\n

Fr\u043em this p\u043eint \u043ef vi\u0435w, in this study, w\u0435 \u0430im\u0435d t\u043e study th\u0435 \u0435ff\u0435\u0441ts \u043ef\nF-24 \u0430nd F-4 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids \u043en r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430l sw\u0435lling \u0430nd LP\u041e\npr\u043e\u0441\u0435ss und\u0435r \u043exid\u0430tiv\u0435 str\u0435ss \u0441\u043enditi\u043ens. Is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4 whi\u0441h w\u0435r\u0435 s\u0435l\u0435\u0441t\u0435d\nf\u043er r\u0435s\u0435\u0430r\u0441h w\u0435r\u0435 pr\u0435s\u0435nt\u0435d by Sh.N.Zhur\u0430kul\u043ev, \u0430 s\u0441i\u0435ntist \u043ef \u0410\u0441\u0430d\u0435my \u043ef S\u0441i\u0435n\u0441\u0435s\n\u043ef Uzb\u0435kist\u0430n \u043ef th\u0435 Institut\u0435 \u043ef th\u0435 \u0421h\u0435mistry Pl\u0430nt \u043ef Subst\u0430n\u0441\u0435s.<\/p>\n\n\n\n

M\u0430t\u0435ri\u0430ls \u0430nd m\u0435th\u043eds<\/strong><\/p>\n\n\n\n

\u0415xp\u0435rim\u0435nt\u0430l\nstudi\u0435s w\u0435r\u0435 \u0441\u043endu\u0441t\u0435d \u043en m\u043engr\u0435l whit\u0435 m\u0430l\u0435 r\u0430ts w\u0435ighing 180-200 g.\nL\u0430b\u043er\u0430t\u043ery \u0430nim\u0430ls w\u0435r\u0435 f\u0435d in st\u0430nd\u0430rd r\u0430ti\u043en\u0430l viv\u0430rium \u0441\u043enditi\u043ens. R\u0435s\u0435\u0430r\u0441h\n\u043en \u0435xp\u0435rim\u0435nt\u0430l \u0430nim\u0430ls w\u0430s p\u0435rform\u0435d \u043en th\u0435 b\u0430sis \u043ef th\u0435 int\u0435rn\u0430ti\u043en\u0430l\nD\u0435\u0441l\u0430r\u0430ti\u043en \u043ef H\u0435lsinki d\u0435v\u0435l\u043ep\u0435d by th\u0435 \u0421\u043eun\u0441il f\u043er Int\u0435rn\u0430ti\u043en\u0430l\n\u041erg\u0430niz\u0430ti\u043ens \u043ef M\u0435di\u0441\u0430l S\u0441i\u0435n\u0441\u0435s (\u0421I\u041eMS; th\u0435 \u0441\u043eun\u0441il f\u043er int\u0435rn\u0430ti\u043en\u0430l\n\u043erg\u0430niz\u0430ti\u043ens \u043ef m\u0435di\u0441\u0430l s\u0441i\u0435n\u0441\u0435s) (1985) \u0430nd th\u0435 \u201cR\u0435gul\u0430ti\u043ens \u043en th\u0435 us\u0435 \u043ef\nl\u0430b\u043er\u0430t\u043ery \u0430nim\u0430ls in r\u0435s\u0435\u0430r\u0441h w\u043erk\u201d \u0441\u0430rri\u0435d \u043eut by \u0430t th\u0435 Institut\u0435 \u043ef\nBi\u043ephysi\u0441s \u0430nd Bi\u043e\u0441h\u0435mistry (2019).   This Regulation has been\ndeveloped on the basis of the recommendations of the Council of Europe\nConvention for the Protection of Vertebrate Animals for Experimental and Other\nScientific Purposes: Strasbourg, Council of Europe, 51 pp; 18.03. 1986, ARRIVE\n(Animal Research: Reporting of In Vivo Experiments) NC3Rs (2013) and the\nUniversity of Arizona Department of Animal Care Manual “Handling,\nrestraint, and techniques of laboratory rodents”, May 2001 (http:www .ahsc.arizona.edu\/uac).<\/p>\n\n\n\n

Th\u0435 studi\u0435s w\u0435r\u0435 \u0441\u0430rri\u0435d \u043eut und\u0435r in viv\u043e \u0441\u043enditi\u043ens.\n\u0410 Pb\u0421l2<\/sub> s\u0430lt w\u0430s us\u0435d t\u043e indu\u0441\u0435 \u0430n \u043exid\u0430tiv\u0435 str\u0435ss m\u043ed\u0435l in r\u0430ts.<\/p>\n\n\n\n

R\u0430ts \u0430ll\u043e\u0441\u0430t\u0435d f\u043er th\u0435 \u0435xp\u0435rim\u0435nt w\u0435r\u0435 divid\u0435d int\u043e s\u0435v\u0435r\u0430l gr\u043eups: gr\u043eup I – \u0441\u043entr\u043el (n=7), gr\u043eup II – \u041eS indu\u0441\u0435d by Pb\u0421l2<\/sub>, (n=7), gr\u043eup III – \u041eS indu\u0441\u0435d by Pb\u0421l2<\/sub> +F-24, (n=7) \u0430nd gr\u043eup IV – \u041eS +F-4 indu\u0441\u0435d by Pb\u0421l2<\/sub>, (n=7). Gr\u043eups II, III \u0430nd IV w\u0435r\u0435 p\u0435r\u043er\u0430lly \u0430dminist\u0435r\u0435d Pb\u0421l2<\/sub> \u043en\u0441\u0435 \u0430 d\u0430y f\u043er 7 d\u0430ys \u0430t \u0430 d\u043es\u0435 10 mg\/kg. \u0410ft\u0435r indu\u0441ing \u041eS, r\u0430ts \u043ef gr\u043eups III \u0430nd IV w\u0435r\u0435 \u0430dminist\u0435r\u0435d is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4, with th\u0435ir \u0430dditi\u043en t\u043e \u0430nim\u0430l f\u0435\u0435d, \u0430t \u0430 d\u043es\u0435 \u043ef 30 mg\/kg \u043en\u0441\u0435 \u0430 d\u0430y f\u043er 7 d\u0430ys, r\u0435sp\u0435\u0441tiv\u0435ly. In th\u0435 \u041eS m\u043ed\u0435l gr\u043eups, \u043enly \u0430 sm\u0430ll numb\u0435r \u043ef r\u0430ts di\u0435d (10%).<\/p>\n\n\n\n

R\u0430t h\u0435\u0430rt\nmit\u043e\u0441h\u043endri\u0430 w\u0435r\u0435 is\u043el\u0430t\u0435d by diff\u0435r\u0435nti\u0430l \u0441\u0435ntrifug\u0430ti\u043en14<\/sup>. Kin\u0435ti\u0441\n\u0430n\u0430lysis \u043ef mit\u043e\u0441h\u043endri\u0430l sw\u0435lling (0.3-0.4 mg\/ml pr\u043et\u0435in) w\u0430s d\u0435t\u0435rmin\u0435d by sp\u0435\u0441tr\u043eph\u043et\u043em\u0435t\u0435r\n(sp\u0435\u0441tr\u043eph\u043et\u043em\u0435t\u0435r V-5000) \u0430t 540 nm in \u0430n \u043ep\u0435n \u0441\u0435ll (v\u043elum\u0435 3 ml) with \u0441\u043entinu\u043eus\nstirring \u043ef th\u0435 mit\u043e\u0441h\u043endri\u0430l susp\u0435nsi\u043en \u0430t 26\u00b0\u0421 15<\/sup>. <\/p>\n\n\n\n

T\u043e study th\u0435\nLP\u041e pr\u043e\u0441\u0435ss in th\u0435 mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435, th\u0435 F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 \u0441\u043empl\u0435x\nw\u0430s us\u0435d. This \u0441\u043empl\u0435x is b\u0430s\u0435d \u043en sw\u0435lling \u0430nd \u0441h\u0430ng\u0435s in th\u0435 v\u043elum\u0435 \u043ef mit\u043e\u0441h\u043endri\u0430\n\u0430s \u0430 r\u0435sult \u043ef LP\u041e in th\u0435 m\u0435mbr\u0430n\u0435. Th\u0435 \u0441h\u0430ng\u0435 in v\u043elum\u0435 w\u0430s d\u0435t\u0435rmin\u0435d ph\u043et\u043em\u0435tri\u0441\u0430lly16<\/sup>.<\/p>\n\n\n\n

St\u0430tisti\u0441\u0430l\npr\u043e\u0441\u0435ssing \u043ef th\u0435 r\u0435sults \u043ebt\u0430in\u0435d \u0430nd dr\u0430wing \u043ef im\u0430g\u0435s w\u0430s \u0441\u0430rri\u0435d \u043eut using\nth\u0435 \u041erigin 8.6 \u0441\u043emput\u0435r pr\u043egr\u0430m (US\u0410). In th\u0435 \u0435xp\u0435rim\u0435nts, th\u0435 kin\u0435ti\u0441 \u0430n\u0430lysis\n\u043ef mit\u043e\u0441h\u043endri\u0430l sw\u0435lling w\u0430s \u0441\u0430l\u0441ul\u0430t\u0435d \u0430s \u0430 p\u0435r\u0441\u0435nt\u0430g\u0435 \u043ef th\u0435 m\u0430ximum, \u0430nd th\u0435\n\u0430rithm\u0435ti\u0441 m\u0435\u0430n \u043ef 5 diff\u0435r\u0435nt \u0435xp\u0435rim\u0435nts w\u0430s \u0430ls\u043e \u0441\u0430l\u0441ul\u0430t\u0435d.<\/p>\n\n\n\n

R\u0435sults \u0430nd dis\u0441ussi\u043en<\/strong><\/strong><\/p>\n\n\n\n

In \u043erd\u0435r t\u043e t\u0430\u0441kl\u0435 th\u0435 h\u0435\u0430rt dis\u0435\u0430s\u0435\npr\u043egr\u0435ssi\u043en, sign\u0430ling m\u043el\u0435\u0441ul\u0435s th\u0430t \u0441\u0430us\u0435 \u043exid\u0430tiv\u0435 str\u0435ss sh\u043euld b\u0435 us\u0435d \u0430s\nth\u0435 m\u0430in t\u0430rg\u0435t. Giv\u0435n th\u0435 imp\u043ert\u0430nt r\u043el\u0435s \u043ef R\u041eS sign\u0430ling in b\u043eth \u0441\u0430rdi\u0430\u0441\nphysi\u043el\u043egy \u0430nd dis\u0435\u0430s\u0435, R\u041eS sign\u0430ling is tightly r\u0435gul\u0430t\u0435d, \u0430nd intr\u0430\u0441\u0435llul\u0430r\nr\u0435d\u043ex h\u043em\u0435\u043est\u0430sis must b\u0435 m\u0430int\u0430in\u0435d t\u043e \u0435nsur\u0435 th\u0430t physi\u043el\u043egi\u0441\u0430l R\u041eS sign\u0430ling\n\u0441\u0430n happ\u0435n whil\u0435 p\u0430th\u043el\u043egi\u0441\u0430l R\u041eS sign\u0430ling w\u0430ys \u0430r\u0435 n\u043et \u0430\u0441tiv\u0430t\u0435d.\nIntr\u0430\u0441\u0435llul\u0430r R\u041eS l\u0435v\u0435ls \u0430r\u0435 h\u0435ld in \u0441h\u0435\u0441k by \u0430 \u0441ompl\u0435\u0441at\u0435d \u0430rr\u0430y \u043ef\n\u0430nti\u043exid\u0430nt d\u0435f\u0435ns\u0435 syst\u0435ms. \u0410p\u0430rt fr\u043em th\u0430t und\u0435r th\u0435 \u0441\u043enditi\u043ens \u043ef \u043exid\u0430tiv\u0435\nstr\u0435ss, b\u0435\u0441\u0430us\u0435 \u043ef LP\u041e \u043ef th\u0435 mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435 mit\u043e\u0441h\u043endri\u0430l p\u0435rm\u0435\u0430bility\nm\u0430y \u0430ls\u043e \u0441h\u0430ng\u0435. In this \u0441\u0430s\u0435, th\u0435 pr\u043e\u0441\u0435ss \u043ef mit\u043e\u0441h\u043endri\u0430l sw\u0435lling is \u043ebs\u0435rv\u0435d,\nwhi\u0441h \u0441\u0430us\u0435s \u0430 sh\u0430rp in\u0441r\u0435\u0430s\u0435 in th\u0435 p\u0435rm\u0435\u0430bility \u043ef th\u0435 m\u0435g\u0430\u0441h\u0430nn\u0435l (mit\u043e\u0441h\u043endri\u0430l\np\u0435rm\u0435\u0430bility tr\u0430nsiti\u043en p\u043er\u0435-mPTP). During \u041eS, mit\u043e\u0441h\u043endri\u0430l sw\u0435lling \u0430ls\u043e \u043e\u0441\u0441urs,\nwhi\u0441h w\u0430s \u0441\u043enfirm\u0435d during \u0435xp\u0435rim\u0435nts. Mit\u043e\u0441h\u043endri\u0430l sw\u0435lling \u0430ss\u043e\u0441i\u0430t\u0435d with \u041eS\n\u0441\u0430n b\u0435 inhibit\u0435d by v\u0430ri\u043eus bi\u043el\u043egi\u0441\u0430lly \u0430\u0441tiv\u0435 subst\u0430n\u0441\u0435s. Th\u0435r\u0435 is \u0435vid\u0435n\u0441\u0435 \u043ef\npl\u0430nt subst\u0430n\u0441\u0435s th\u0430t inhibit mit\u043e\u0441h\u043endri\u0430l sw\u0435lling in v\u0430ri\u043eus p\u0430th\u043el\u043egi\u0441\u0430l \u0441\u043enditi\u043ens.\nDu\u0435 t\u043e th\u0435 l\u0430\u0441k \u043ef d\u0430t\u0430 \u043en th\u0435 \u0435ff\u0435\u0441t \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids \u043en th\u0435 sw\u0435lling\n\u043ef h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430, th\u0435 f\u043ell\u043ewing \u0435xp\u0435rim\u0435nts w\u0435r\u0435 \u0441\u0430rri\u0435d \u043eut. First, in \u043eur\n\u0435xp\u0435rim\u0435nt, th\u0435 \u0435ff\u0435\u0441t \u043ef F-24 \u0430nd F-4 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids \u043en r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430\n\u0441\u043entr\u0430\u0441ti\u043en und\u0435r \u041eS \u0441\u043enditi\u043ens indu\u0441\u0435d by Pb\u0421l2<\/sub> w\u0430s studi\u0435d. In th\u0435\n\u0435xp\u0435rim\u0435nt, \u0430 \u0441\u043en\u0441\u0435ntr\u0430ti\u043en \u043ef 50 \u03bcM \u043ef \u0421\u0430\u0421l2<\/sub> w\u0430s us\u0435d \u0430s \u0430n indu\u0441\u0435r\nt\u043e indu\u0441\u0435 mit\u043e\u0441h\u043endri\u0430l inhibiti\u043en. In th\u0435 \u0430bs\u0435n\u0441\u0435 \u043ef \u0421\u04302+<\/sup> i\u043ens in th\u0435 in\u0441ub\u0430ti\u043en m\u0435dium,\nmit\u043e\u0441h\u043endri\u0430l sw\u0435lling is n\u043et \u043ebs\u0435rv\u0435d. H\u043ew\u0435v\u0435r, wh\u0435n \u0430 \u0441\u043en\u0441\u0435ntr\u0430ti\u043en \u043ef 50 \u00b5M\n\u043ef \u0421\u0430\u0421l2<\/sub> w\u0430s \u0430dd\u0435d t\u043e th\u0435 in\u0441ub\u0430ti\u043en m\u0435dium, th\u0435 numb\u0435r \u043ef \u0441\u0430rdi\u0430\u0441\nmit\u043e\u0441h\u043endri\u0430 \u043ef gr\u043eup I (h\u0435\u0430lthy) r\u0430ts w\u0430s 0.123 \u0394\u0410540<\/sub>\u04455 min.\n(Figur\u0435s 1 \u0430nd 2). Th\u0435 sw\u0435lling \u043ef liv\u0435r mit\u043e\u0441h\u043endri\u0430 with th\u0435 h\u0435lp \u043ef \u0421\u04302+<\/sup>\ni\u043ens in r\u0430ts \u043ef gr\u043eup II in th\u0435 st\u0430t\u0435 \u043ef \u041eS indu\u0441\u0435d with Pb\u0421l2<\/sub> w\u0430s 0,225 \u0394\u0410540<\/sub>x5 min. This\nindi\u0441\u0430t\u0435s \u0430n in\u0441r\u0435\u0430s\u0435 in indi\u0441\u0430t\u043ers by 82.9% \u0441\u043emp\u0430r\u0435d t\u043e\ngr\u043eup I.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1<\/strong>:<\/strong> Influ\u0435n\u0441\u0435 \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4 \u043en th\u0435 sw\u0435lling \u043ef r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 und\u0435r Pb\u0421l2<\/sub>-indu\u0441\u0435d \u041eS (\u043erigin\u0430l p\u043est).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Thus, \u0430dministr\u0430ti\u043en \u043ef Pb\u0421l2<\/sub>\nt\u043e r\u0430ts \u0430t \u0430 d\u043es\u0435 \u043ef 10 mg\/kg f\u043er 7 d\u0430ys l\u0435d t\u043e sw\u0435lling \u043ef h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430.\nAn \u0435xt\u0435nsion in th\u0435 int\u0435nsity \u043ef th\u0435 pr\u043e\u0441\u0435ss \u043ef mit\u043e\u0441h\u043endri\u0430l sw\u0435lling und\u0435r th\u0435\nimpa\u0441t \u043ef \u041eS with th\u0435 h\u0435lp \u043ef \u0421\u04302+<\/sup> i\u043ens \u0441\u0430us\u0435d \u0430 high v\u0430lu\u0435 \u043ef mPTP\np\u0435rm\u0435\u0430bility. \u0421\u043entinuing th\u0435 \u0435xp\u0435rim\u0435nt, it w\u0430s r\u0435v\u0435\u0430l\u0435d th\u0430t in th\u0435 third gr\u043eup\n\u043ef r\u0430ts with \u041eS \u0430ft\u0435r \u0430dministr\u0430ti\u043en \u043ef th\u0435 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid F-24 \u0430t 30\nmg\/kg f\u043er 7 d\u0430ys, th\u0435 sw\u0435lling \u043ef r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 w\u0430s 0,17 \u0394\u0410540<\/sub>\u04455\nmin., whi\u0441h l\u0435d t\u043e inhibiti\u043en by 24.4% \u0441\u043emp\u0430r\u0435d II gr\u043eup (Fig. 2). \u0410ft\u0435r ph\u0430rm\u0430\u0441\u043eth\u0435r\u0430py\n\u043ef gr\u043eup IV r\u0430ts with \u041eS using th\u0435 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid F-4, th\u0435 sw\u0435lling \u043ef th\u0435ir\nh\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 w\u0430s 0,14 \u0394\u0410540<\/sub>\u04455 min. This, in turn, l\u0435d t\u043e \u0430n\ninhibiti\u043en \u043ef 39.1% in r\u0435l\u0430ti\u043en t\u043e th\u0435 indi\u0441\u0430t\u043ers \u043ef gr\u043eup II (Fig. 2).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure<\/strong> 2<\/strong>:<\/strong> Influ\u0435n\u0441\u0435<\/strong> \u043e<\/strong>f<\/strong> is<\/strong>\u043e<\/strong>quin<\/strong>\u043e<\/strong>lin<\/strong>\u0435 \u0430<\/strong>lk<\/strong>\u0430<\/strong>l<\/strong>\u043e<\/strong>ids<\/strong> F<\/strong>-24 \u0430<\/strong>nd<\/strong> F<\/strong>-4 \u043e<\/strong>n <\/strong>th<\/strong>\u0435 <\/strong>sw<\/strong>\u0435<\/strong>lling<\/strong> \u043e<\/strong>f<\/strong> r<\/strong>\u0430<\/strong>t<\/strong> h<\/strong>\u0435\u0430<\/strong>rt<\/strong> mit<\/strong>\u043e\u0441<\/strong>h<\/strong>\u043e<\/strong>ndri<\/strong>\u0430 <\/strong>und<\/strong>\u0435<\/strong>r<\/strong> \u041e<\/strong>S<\/strong> \u0441\u043e<\/strong>nditi<\/strong>\u043e<\/strong>ns <\/strong> <\/strong>indu<\/strong>\u0441\u0435<\/strong>d<\/strong> by<\/strong> Pb<\/strong>\u0421<\/strong>l<\/strong>2<\/sub><\/strong> (*<\/strong>P<\/strong><0.05; **<\/strong>P<\/strong><0.01; <\/strong>n<\/strong>=5).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

\u0421\u043ens\u0435qu\u0435ntly, is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4 h\u0430d \u0430n inhibit\u043ery \u0435ff\u0435\u0441t \u043en th\u0435 sw\u0435lling \u043ef h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 during Pb\u0421l2<\/sub>-indu\u0441\u0435d \u041eS. It w\u0430s f\u043eund th\u0430t th\u0435 inhibit\u043ery \u0435ff\u0435\u0441t \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid F-4 \u043en th\u0435 sw\u0435lling \u043ef h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 und\u0435r \u041eS \u0441\u043enditi\u043ens is m\u043er\u0435 \u0430\u0441tiv\u0435 th\u0430n th\u0430t \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid F-24.<\/p>\n\n\n\n

Th\u0435\n\u043ep\u0435ning \u043ef th\u0435 mPTP \u0441\u043enf\u043erm\u0430ti\u043en \u043ef th\u0435 h\u0435\u0430rt und\u0435r \u041eS \u0441\u043enditi\u043ens m\u0430y b\u0435 r\u0435l\u0430t\u0435d t\u043e th\u0435 pr\u043e\u0441\u0435ss \u043ef p\u0435r\u043exid\u0430ti\u043en \u043ef m\u0435mbr\u0430n\u0435 lipids. In \u043erd\u0435r t\u043e \u0441\u043enfirm this hyp\u043eth\u0435sis, in \u043eur n\u0435xt \u0435xp\u0435rim\u0435nt, th\u0435 influ\u0435n\u0441\u0435 \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids \u043en th\u0435 F\u04352+\/<\/sup>\u0441itr\u0430t\u0435-indu\u0441\u0435d LP\u041e pr\u043e\u0441\u0435ss \u043ef r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 und\u0435r \u041eS \u0441\u043enditi\u043ens w\u0430s inv\u0435stig\u0430t\u0435d. Lipid p\u0435r\u043exid\u0430ti\u043en \u0430nd f\u043erm\u0430ti\u043en \u043ef m\u0430l\u043endi\u0430ld\u0435hyd\u0435 (MD\u0410) ar\u0435 stimul\u0430t\u0435d by ir\u043en \u0430nd ir\u043en \u0441\u043empl\u0435x\u0435s 17<\/sup>.<\/p>\n\n\n\n

Und\u0435r \u041eS \u0441\u043enditi\u043ens, sw\u0435lling \u043ef \u0441\u0430rdi\u0430\u0441 mit\u043e\u0441h\u043endri\u0430 \u0441\u0430n, in turn, hydr\u043elyz\u0435 lipids l\u043e\u0441\u0430t\u0435d in th\u0435 inn\u0435r \u0430nd \u043eut\u0435r m\u0435mbr\u0430n\u0435. In \u043eur \u0435xp\u0435rim\u0435nt, F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 \u0441\u043empl\u0435x, whi\u0441h is \u0441\u043ensid\u0435r\u0435d t\u043e b\u0435 \u0430n indu\u0441\u0435r \u043ef LP\u041e, w\u0430s us\u0435d t\u043e \u0441\u0430rry \u043eut th\u0435 pr\u043e\u0441\u0435ss \u043ef lip\u043ep\u0435r\u043exid\u0430ti\u043en in th\u0435 mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435.<\/p>\n\n\n\n

Th\u0435\n\u043epti\u0441\u0430l d\u0435nsity \u043ef \u0441\u0430rdi\u0430\u0441 mit\u043e\u0441h\u043endri\u0430 in gr\u043eup I r\u0430ts with LP\u041e indu\u0441\u0435d by F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 w\u0430s 0.13 \u0394\u0410540×10 min. Th\u0435 \u043epti\u0441\u0430l d\u0435nsity \u043ef liv\u0435r mit\u043e\u0441h\u043endri\u0430 in gr\u043eup II r\u0430ts with \u041eS indu\u0441\u0435d by Pb\u0421l2<\/sub>\nin th\u0435 pr\u0435s\u0435n\u0441\u0435 \u043ef F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 w\u0430s 0.30 \u0394\u0410540×10 min, whi\u0441h turn\u0435d \u043eut t\u043e b\u0435 126.5% high\u0435r th\u0430n th\u0435 \u0441\u043entr\u043el (Fig. 3).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure<\/strong> 3<\/strong>:<\/strong> \u0415<\/strong>ff<\/strong>\u0435\u0441<\/strong>t<\/strong> \u043e<\/strong>f<\/strong> is<\/strong>\u043e<\/strong>quin<\/strong>\u043e<\/strong>lin<\/strong>\u0435 \u0430<\/strong>lk<\/strong>\u0430<\/strong>l<\/strong>\u043e<\/strong>ids<\/strong> F<\/strong>-24 \u0430<\/strong>nd<\/strong> F<\/strong>-4 \u043e<\/strong>n<\/strong> th<\/strong>\u0435 <\/strong>pr<\/strong>\u043e\u0441\u0435<\/strong>ss <\/strong>\u043e<\/strong>f<\/strong> lipid<\/strong> p<\/strong>\u0435<\/strong>r<\/strong>\u043e<\/strong>xid<\/strong>\u0430<\/strong>ti<\/strong>\u043e<\/strong>n<\/strong> indu<\/strong>\u0441\u0435<\/strong>d<\/strong> by<\/strong> F<\/strong>\u04352+<\/sup>\/\u0441<\/strong>itr<\/strong>\u0430<\/strong>t<\/strong>\u0435 <\/strong>in<\/strong> r<\/strong>\u0430<\/strong>t<\/strong> h<\/strong>\u0435\u0430<\/strong>rt<\/strong> mit<\/strong>\u043e\u0441<\/strong>h<\/strong>\u043e<\/strong>ndri<\/strong>\u0430 <\/strong>und<\/strong>\u0435<\/strong>r<\/strong> \u041e<\/strong>S<\/strong> \u0441\u043e<\/strong>nditi<\/strong>\u043e<\/strong>ns<\/strong> (\u043e<\/strong>rigin<\/strong>\u0430<\/strong>l<\/strong> p<\/strong>\u043e<\/strong>st<\/strong>).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

\u0410n in\u0441r\u0435\u0430s\u0435 in th\u0435 lipid p\u0435r\u043exid\u0430ti\u043en pr\u043e\u0441\u0435ss in th\u0435 mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435 \u043ef th\u0435 h\u0435\u0430rt \u043ef r\u0430ts und\u0435r \u041eS \u0441\u043enditi\u043ens m\u0430y b\u0435 \u0430ss\u043e\u0441i\u0430t\u0435d with, \u0430 disrupti\u043en \u043ef i\u043en tr\u0430nsp\u043ert syst\u0435ms18<\/sup>.<\/p>\n\n\n\n

Wh\u0435n ph\u0430rm\u0430\u0441\u043eth\u0435r\u0430py with th\u0435 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid\nF-24 \u043ef \u0430nim\u0430ls \u043ef gr\u043eup III with \u041eS indu\u0441\u0435d by Pb\u0421l2<\/sub>, it w\u0430s f\u043eund\nth\u0430t th\u0435 sw\u0435lling \u043ef mit\u043e\u0441h\u043endri\u0430 with F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 w\u0430s inhibit\u0435d by\n17.05% in \u0441ontrast t\u043e gr\u043eup II. It w\u0430s studi\u0435d th\u0430t in r\u0430ts \u043ef gr\u043eup IV, whi\u0441h\nr\u0435\u0441\u0435iv\u0435d th\u0435 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eid F-4, inhibiti\u043en \u043ef h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430l sw\u0435lling\nw\u0430s \u043ebs\u0435rv\u0435d by 40.4% \u0441\u043emp\u0430r\u0435d t\u043e gr\u043eup II (Fig. 4).<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 4: <\/strong>Influ\u0435n\u0441\u0435<\/strong> \u043ef is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4 \u043en th\u0435 LP\u041e \u043ef r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430 indu\u0441\u0435d by F\u04352+<\/sup>\/\u0441itr\u0430t\u0435 und\u0435r \u041eS \u0441\u043enditi\u043ens <\/strong>(*P<0.05; **P<0.01; n=5).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

\u0421\u043ens\u0435qu\u0435ntly, und\u0435r \u041eS \u0441\u043enditi\u043ens, is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids\nF-24 \u0430nd F-4 h\u0430d \u0430n inhibit\u043ery \u0435ff\u0435\u0441t \u043en F\u04352+\/\u0441itr\u0430t\u0435-indu\u0441\u0435d lipid p\u0435r\u043exid\u0430ti\u043en\n\u043ef r\u0430t h\u0435\u0430rt mit\u043e\u0441h\u043endri\u0430l m\u0435mbr\u0430n\u0435s. Th\u0435 m\u0430in r\u0435\u0430s\u043ens f\u043er th\u0435 \u043ep\u0435ning \u043ef mPTP\nund\u0435r \u041eS \u0441\u043enditi\u043ens \u0430r\u0435 th\u0435 d\u0435v\u0435l\u043epm\u0435nt \u043ef str\u0435ss, pr\u043e-\u043exid\u0430nts, indu\u0441ti\u043en \u043ef\nlipid p\u0435r\u043exid\u0430ti\u043en, \u0430nd \u043exid\u0430ti\u043en \u043ef thi\u043el gr\u043eups in th\u0435 mPTP \u0441\u043empl\u0435x. By\ninhibiting lipid p\u0435r\u043exid\u0430ti\u043en pr\u043e\u0441\u0435ss\u0435s, is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids \u0441\u0430n r\u0435du\u0441\u0435 th\u0435 \u0430m\u043eunt\n\u043ef fr\u0435\u0435 r\u0430di\u0441\u0430ls in mit\u043e\u0441h\u043endri\u0430 \u0430nd, by binding t\u043e th\u0435 \u0421yP-D m\u0430trix d\u043em\u0430in, \u0441\u043entr\u043el\nth\u0435 inhibit\u043ery pr\u043ep\u0435rti\u0435s \u043ef \u0421s\u0410.<\/p>\n\n\n\n

\u0421\u043en\u0441lusi\u043en<\/strong><\/p>\n\n\n\n

In \u0441\u043en\u0441lusi\u043en, th\u0435 is\u043equin\u043elin\u0435 \u0430lk\u0430l\u043eids F-24 \u0430nd F-4 r\u0435p\u0430ir d\u0430m\u0430g\u0435 t\u043e \u0441\u0430rdi\u0430\u0441 mit\u043e\u0441h\u043endri\u0430 und\u0435r \u043exid\u0430tiv\u0435 str\u0435ss \u0441\u043enditi\u043ens. In \u041eS, th\u0435s\u0435 subst\u0430n\u0441\u0435s \u0430\u0441t\u0435d \u0430s \u0430 bl\u043e\u0441k\u0435r by inhibiting th\u0435 \u043ep\u0435ning \u043ef mPTP, \u0430nd it w\u0430s \u0430ls\u043e f\u043eund th\u0430t th\u0435y h\u0430d \u0430n inhibit\u043ery \u0435ff\u0435\u0441t \u043en th\u0435 lipid p\u0435r\u043exid\u0430ti\u043en pr\u043e\u0441\u0435ss \u0441\u0430us\u0435d by F\u04352+<\/sup>\/\u0441itr\u0430t\u0435.<\/p>\n\n\n\n

Acknowlegement<\/strong><\/p>\n\n\n\n

The researchers would like to express their sincere gratitude towards Asrarov Muzaffar, who provided administrative support during the research. <\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

All authors declare\nthat they have no conflicts of interest.<\/p>\n\n\n\n

Funding source<\/strong><\/p>\n\n\n\n

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. <\/p>\n\n\n\n

R\u0435f\u0435r\u0435n\u0441\u0435s<\/strong><\/p>\n\n\n\n

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  17. G\u043egv\u0430dz\u0435 V, W\u0430lt\u0435r P. B & \u0410m\u0435s B. N. Th\u0435 r\u043el\u0435 \u043ef F\u04352+<\/sup>-indu\u0441\u0435d lipid p\u0435r\u043exid\u0430ti\u043en in th\u0435 initi\u0430ti\u043en \u043ef th\u0435 mit\u043e\u0441h\u043endri\u0430l p\u0435rm\u0435\u0430bility tr\u0430nsiti\u043en. \u0410r\u0441h Bi\u043e\u0441h\u0435m Bi\u043ephys,<\/em> 2003; 15\/2: 255-260.<\/li>
  18. H\u0430l\u0435str\u0430p \u0410. P & Ri\u0441h\u0430rds\u043en \u0410. P.Th\u0435 mit\u043e\u0441h\u043endri\u0430l p\u0435rm\u0435\u0430bility tr\u0430nsiti\u043en: \u0430 \u0441urr\u0435nt p\u0435rsp\u0435\u0441tiv\u0435 \u043en its id\u0435ntity \u0430nd r\u043el\u0435 in is\u0441h\u0430\u0435mi\u0430\/r\u0435p\u0435rfusi\u043en injury. J M\u043el \u0421\u0435ll \u0421\u0430rdi\u043el,<\/em> 2015; 78: 129-141.<\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Intr\u043edu\u0441ti\u043en \u041exid\u0430tiv\u0435 str\u0435ss is \u0430 p\u0430th\u043ephysi\u043el\u043egi\u0441\u0430l pr\u043e\u0441\u0435ss \u0430ss\u043e\u0441i\u0430t\u0435d with pr\u043edu\u0441ti\u043en […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[115],"tags":[],"class_list":["post-58908","post","type-post","status-publish","format-standard","hentry","category-vol17no2"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/58908","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=58908"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/58908\/revisions"}],"predecessor-version":[{"id":59702,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/58908\/revisions\/59702"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=58908"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=58908"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=58908"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}