Sichqonlarda CCl4-mast bo'lgan buyrak, o'pka, miya va taloqdagi urug'siz qora Vitis Vinifera polifenollari orqali ROS/NF‑KB signalizatsiya yo'lini nishonga olish
Mar 27, 2022
Qo'shimcha ma'lumot uchun. aloqatina.xiang@wecistanche.com
Oksidativ stressreaktiv kislorod turlari (ROS) toksikligi va fiziologik o'rtasidagi nomutanosiblik sifatida aniqlanadi.antioksidantROSni yo'q qiladigan yoki zararni yaxshilaydigan mudofaa tizimi, hujayraning barcha tomonlarini yo'q qiladigan hosil bo'lgan ROS halokatli ta'sirga olib kelishi mumkin,2 va insonning ko'plab organlari, jumladan, miya, o'pka, jigar, taloq va patogenezda muhim rol o'ynaydi. buyrak-5. Binobarin, ROS ishlab chiqarishni kamaytirish ko'proq oksidlovchi shikastlanishning oldini olish uchun juda muhimdir va; hujayraning omon qolishi uchun. Shunga qaramay, katta hujayra shikastlanishi atrofdagi sog'lom hujayralarni saqlab qolish uchun shikastlangan hujayraning olib tashlanishiga olib keladi6, Metanol, uglerod tetraklorid (CC1,) kabi turli xil zaharli kimyoviy moddalar. aromatik uglevodorodlar va bromobenzol ROS8 ishlab chiqarish orqali tizimli organlarning shikastlanishiga olib kelishi mumkin. CCl uy sharoitida ham, sanoatda ham tozalovchi, erituvchi va yog'sizlantiruvchi sifatida keng qo'llanilgan. Bundan tashqari, u o'simlik ekstraktlari va dorilarning gepatotoksik ta'sirini o'rganish uchun eksperimental model sifatida keng qo'llaniladi, chunki jigar CCl, toksik ta'sirga duchor bo'lgan asosiy organ hisoblanadi. Uning toksikligi boshqa organlarga ham ta'sir qilishi mumkin, masalanbuyrak, o'pka vataloq.
Laboratoriya hayvonlari modellarida turli xil surunkali kasalliklar, toksinlar va zaharli kimyoviy moddalardan himoya qilish qobiliyati uchun ko'plab an'anaviy dori vositalari o'rganilgan-4. Vitis vinifera (VV) - Vitaceae oilasiga tegishli bo'lgan o'simliklar va funktsional oziq-ovqatlardan biri. Bu klimakterik bo'lmagan meva va dunyodagi eng ko'p yetishtiriladigan va iste'mol qilinadigan yeyiladigan meva. VV immunitetni kuchaytiruvchi, yallig'lanishga qarshi, neyroprotektiv, antioksidant, apoptotik va antikanserogen kabi turli xil sog'liq uchun foydali ta'sirga ega. Ushbu rag'batlantiruvchi ta'sirlar minerallar, aminokislotalar, oqsillar, shakarlar, organik kislotalar, vitaminlar va fitokimyoviy moddalarni (flavonoidlar, karotenoidlar, taninlar, antosiyaninlar va proantosianinlar) o'z ichiga olgan funktsional tarkibiy qismlarga bog'liq.
VV ning poyalari, barglari, urug'lari va sharbatlari kabi turli turlari va qismlarini turli xil gepatotoksik agentlarga, shu jumladan CCl ga qarshi himoya qilish kuchi tekshirildi-5,17. Bundan tashqari, bizning yaqinda nashr etilgan ishimiz o'rganildi. birinchi marta, ekstraksiya qilingan urug'siz (ham pulpa, ham teri) qora VV polifenollarining (VVP) CCl tomonidan qo'zg'atilgan gepatotoksisitega qarshi gipnoterapevtik potentsiali va sinergik faolligi². Yaxshiyamki, avvalgi hech qanday tadqiqot VAV-CCl tizimining terapevtik samaradorligini o'rganishga urinilmagan. kalamushlarda toksikligi (buyrak, o'pka, miya va taloq toksikligi), ularning ushbu maqsadli organlardagi terapevtik qiymatlarini solishtirish uchun.Shuning uchun joriy tadqiqot to'rtta ushbu izolyatsiya qilingan polifenollarning terapevtik potentsialini solishtirishdan tashqari, ushbu nuqtani o'rganish uchun o'tkazildi. Qora VVP ning CCl tizimli destruktsiyani keltirib chiqaradigan oksidlovchi shikastlanish va nekroinflamasyonga ta'siri ham baholandi. Bu yerda. Natijalarni tushuntirish uchun VVP ning fitokimyoviy tarkibi va in vitro antioksidant faolligi tekshirildi.
Natijalar
VVPF ning fenolik tarkibi va antioksidant salohiyati.Ushbu tadqiqot VVPF ning umumiy fenolik miqdori 58,387 ± 0, 755 mg gallik kislota ekv. g-'VV PF. Bundan tashqari, ushbu tadqiqotda flavonoidlarda 16,718±1,858 mg katexin, 1.098±{15}},342 mg Quercetin(QR) ekv flavanol va 3,467±0,466 mg siyanidin{{ 17}}glyukozid (Cy{18}}GLC) har 1 g VVPFda antosiyaninlar ekvi.
VVPF jami antioksidant sig'imi (TAC) qiymati 709,589±25,939 mg Butillangan gidroksitoluen (BHT) ga teng bo'lgan kuchli in vitro antioksidant faolligini ko'rsatdi. g-1VVPE. Bundan tashqari, u kuchli temirni kamaytiruvchi kuchga ega va 2,2'-azino-bis(3-etilbenzotiazolin-6-sulfonik kislota (ABTS) radikalini tozalashga qodir edi (1A, B-rasm). Natijalar ham VVPF ning temir kamaytiruvchi kuchi sezilarli darajada ekanligini ko'rsatdi (p<0.05)higher(lower ic50="" value="" "50%="" inhibitory="" concentration")="" than="" that="" of="" ascorbic="" acid="" (asc),="" while="" its="" abts="" scavenging="" power="" was="" lower="" (higher="" ic50="" value)="" than="" that="" of="">
VVPF ning CCl tomonidan qo'zg'atilgan tizimli toksikligiga ta'siri.VVPF buyrak, o'pka, miya va taloq to'qimalarida CCl toksikligiga kuchli yaxshilovchi ta'sir ko'rsatdi. Bu tizimlilikning sezilarli yaxshilanishi bilan namoyon bo'ldioksidlovchi stressvaneyro yallig'lanish.
Natijalar shuni ko'rsatdiki, buyrak, o'pka va organ uchun og'irlik / kuch nisbatitaloqto'qimalarda barcha guruhlar o'rtasida sezilarli bo'lmagan o'zgarishlar mavjud edi. Biroq, muhim (p<0.05)decrease was="" detected="" in="" the="" brain="" wt/b.w.ratios="" of="" rats="" in="" ccl(39.891%)and="" v(45.355%)="" groups="" as="" compared="" to="" the="" control="" "c"="" group.="" however,="" there="" was="" an="" anon-significant="" change="" in="" these="" ratios="" in="" rats="" of="" the="" ccl,+vvpf="" group="" relative="" to="" the="" ccl="" group="" (fig.="">
VVPF ning CCl tomonidan kelib chiqqan buyrak oksidlovchi stressiga yaxshilovchi ta'siri.Ushbu tadqiqot ma'lumotlari shuni ko'rsatdiki, CCl buyrakda oksidlovchi stressni keltirib chiqardi, bu sezilarli darajada namoyon bo'ldi (p).<0.05)elevation in="" the="" level="" of="" ros(203.169%)and="" no(545.833%).in="" addition,="" the="">CCl guruhida kislotali reaktiv moddalar (TBARS, 321,790 foiz) darajasi va miyeloperoksidaza faolligi (MPO, 321,579 foiz) C guruhiga nisbatan oshdi (2A-C-rasm). Bu natijalar TAC (53,121 foiz) darajasining keskin pasayishi va glutation (GSH,80,647 foiz) va fermentativ antioksidantlar (superoksid dismutaza "SOD, 45,727 foiz" va glutation peroksidaza" GPX, foiz 0,95) faolligining keskin pasayishi bilan birga keldi. ") Fig.2A, C, D da ko'rsatilgandek. Biroq, V "avtomobil" guruhidagi kalamushlarning buyragida bu oksidlanish stress belgilarining barchasida sezilarli bo'lmagan o'zgarish bo'lgan (Fig.2A-D).
![Te improving activity of VVPF to CCl4-induced renal oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the kidney tissues. Results are expressed as mean±S.E of 7 animals. C Control untreated rats; CCl4 rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene](/Content/uploads/2022842169/20220324141803714ee4ff12da46fb85e3d4af180e6971.png "Te improving activity of VVPF to CCl4-induced renal oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the kidney tissues. Results are expressed as mean±S.E of 7 animals. C Control untreated rats; CCl4 rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene")
Ushbu tadqiqot VVPFni o'n kun davomida (CCl va VVPF guruhi) qo'llashdan so'ng oksidlovchi stress parametrlarida yaxshi yaxshilanish haqida xabar berdi. Shuning uchun ROS, NO va TBARS darajalari va MPO faolligi sezilarli darajada edi (p).<0.05)reduced relative="" to="" that="" of="" the="" ccl,group="" by="" 44.747%,81.297%,67.439%,and="" 35.362%,="" respectively(fig.2a-c).in="" contrast,="" the="" level="" of="" tac(47.429%)="" and="" gsh(81.899%)and="" the="" activity="" of="" sod="" (57.936%)="" and="" gpx(91.769%)were=""><0.05) upregulated="" in="" the="" kidney="" of="" the="" rats="" in="" this="" group="" (fig.2a,="" c,="" d).="" while="" the="" intake="" of="" vvpf="" alone="" for="" ten="" days(vvpfgroup)had="" an="" anon-significant="" effect="" on="" all="" of="" the="" previous="" parameters,="" except="" for="" the="" mpo(decrease="" by="" 31.513%)and="" sod(elevated="" by="" 17.413%)="" activities,="" which="" were="" significantly=""><0.05) changed="" as="" related="" to="" the="" control="">
VVPF ning o'pkada CCl keltirib chiqaradigan oksidlovchi stressga yaxshilovchi ta'siri.O'pkada CCl, shuningdek, ROS, NO darajasini ko'tarish orqali oksidlovchi stressni keltirib chiqardi. T-BARS. va MPO faolligi sezilarli darajada (s<0.05),by 131.883%,516.092%,332.458%,and="" 57.319%,respectively="" as="" compared="" to="" the="" control="" rats(fig.3a-c).="" moreover,="" the="" level="" of="" tac(65.779%),="" gsh(81.081%),="" as="" well="" as="" the="" activity="" of="" both="" sod="" (53.195%)and="" gpx="" (66.797%)were="" greatly="" depleted="" in="" the="" lung="" after="" ccl,="" injection(fig.3a,="" c,="" d).="" the="" results="" also="" found="" that="" the="" injection="" of="" rats="" with="" olive="" oil="" for="" 3="" weeks(v="" group)led="" to="" a="" significant=""><0.05)increase in="" the="" ros="" and="" tbars="" levels.="" moreover,="" it="" substantially="" diminished="" the="" tac="" and="" gsh="" contents="" in="" addition="" to="" the="" sod="" and="" gpx="" activities,="" relative="" to="" the="" control="" (fig.="" 3a-d).="" the="" percentages="" of="" these="" changes="" were="" 38.146%,="" 23.430%,34.877%,19.018%,41.998%,="" and="" 15.715%,="">
VVPFni o'n kun davomida yuborish (CCl, plus VVPF guruhi) CCl tomonidan qo'zg'atilgan o'pkaning redoks holatidagi buzilishlarni sezilarli darajada yaxshiladi. Bunga sezilarli (p) erishildi.<0.05) decrease="" in="" the="" ros,="" no,and="" tbars="" levels,="" and="" mpo="" activity="" by="" 65.510%,58.955%,75.435%,and="" 55.496%,respectively,="" as="" related="" to="" the="" ccl,="" group="" (fig.3a-c).="" however,="" the="" levels="" of="" tac="" (136.084%)="" and="" gsh(445.627%),as="" well="" as="" the="" activity="" of="" sod(137.817%)and="" gpx(166.154%)were="" significantly=""><0.05)upregulated (fig.3a,c,d).while="" the="" administration="" of="" vvpf="" alone="" for="" ten="" days(vvpf="" group)="" not="" only="" had="" no="" damaging="" effect="" on="" the="" lung="" but="" also="" enhanced="" the="" pulmonary="" redox="" state.="" this="" has="" clearly="" appeared="" from="" its="" ability="" to="" enormously="" decrease="" the="" mpo="" activity(53.951%)="" and="" increase="" the="" gsh="" level(5.854%)and="" gpx="" activity(54.323%),="" as="" compared="" to="" the="" control="" untreated="" rats="" (fig.="" 3c,="">
VVPF ning miyadagi CCl tomonidan qo'zg'atilgan oksidlovchi stressga yaxshilovchi ta'siri. 4-rasmda CCl ning kalamush miyasining hujayrali redoks holatida nomutanosiblikni keltirib chiqarish qobiliyati ko'rsatilgan. Bu ROS (198,719 foiz), NO (140,580 foiz) va TBARS (461,917 foiz) va MPO faolligi (98,253 foiz) ning C guruhi bilan bog'liq bo'lgan hujayra tarkibining katta ko'tarilishi bilan izohlanadi (1-rasm). 4A-C). Aksincha, TAC (66,333 foiz) va GSH miqdori (63,233 foiz), SOD (37,463 foiz) va GPX (38,788 foiz) faolligi davolanmagan nazorat kalamushlari bilan solishtirganda keskin kamaydi (4A-rasm). C, D). Ma'lumotlar, shuningdek, zaytun moyi 3 hafta davomida (V guruh) qo'llanganda toksik ta'sirini aniqladi. Bu toksiklik uning ROS (49,829 foiz) va TBARS (15,612 foiz) darajalariga ta'siri, TAC (44,444 foiz) va GSH (29,822 foiz) darajalari, shuningdek, SOD (30,741 foiz) va GPX513,013 foizga pasayishi bilan bog'liq. faoliyati C guruhi bilan solishtirganda (Fig.4A-D).
VVPFni o'n kun davomida yuborish (CCl, plus VVPF guruhi) CCl, infektsiyadan kelib chiqqan miya oksidlovchi stress holatini yaxshilash uchun etarli edi. VVPFintakedan keyin ROS darajasi (37,175 foiz). NO(47,879 foiz) .TBARS (69,551 foiz), shuningdek MPO (66,516 foiz) faolligi CCl guruhi bilan bog'liq bo'lganda keskin pasaydi (4A-C-rasm). Bundan tashqari, TAC va GSH darajalari, shuningdek, SOD va GPX faoliyati sezilarli darajada edi (p<0.05)elevated when="" compared="" to="" the="" rats="" in="" the="" ccl,="" group="" (fig.4a,="" c,="" d).the="" percentages="" of="" increase="" were="" 95.544%,105.136%,71.815%,and="" 41.951%,respectively.on="" the="" other="" hand,="" the="" intake="" of="" vvpf="" alone="" (vvpf="" group)="" had="" no="" toxic="" effects="" on="" the="" brain.="" in="" addition,="" vvpf="" was="" able="" to=""><0.05)increase the="" gsh="" level(22.809%)="" and="" the="" gpx="" activity(14.292%),="" relative="" to="" the="" control="" group="" as="" shown="" in="">
VVPF ning CCl tomonidan qo'zg'atilgan taloq oksidlovchi stressiga yaxshilovchi ta'siri.5-rasmda CCl4 in'ektsiyasining taloqning hujayrali redoks holatiga ta'siri aniqlangan. Nazorat guruhi bilan solishtirganda, 3 haftalik in'ektsiyadan keyin kalamushlarning taloqida ROS (270,080 foiz), NO (182,979 foiz) va TBARS (395,516 foiz) va MPO faolligi (165,852 foiz) sezilarli darajada oshdi. CCl bilan (Fig.5A-C). Bundan tashqari, taloq TAC va ferment bo'lmagan antioksidant (GSH) darajasi, shuningdek, fermentativ antioksidant (SOD va GPX) faolligi sezilarli darajada edi (p).<0.05) decreased="" as="" compared="" to="" the="" c="" group="" (fig.="" 5a,="" c,="" d).the="" percentages="" of="" this="" decrease="" were="" 64.035%,74.867%,35.894%,and="" 77.092%,respectively.="" however,="" no="" dramatic="" changes="" were="" observed="" in="" the="" spleens="" of="" rats="" after="" injection="" with="" olive="" oil="" (v="">
Bizning ma'lumotlarimiz shuni ko'rsatdiki, CCl in'ektsiyasidan keyin o'n kun davomida VVPF bilan davolash (CCl, plus VVPF guruhi) taloqning oksidlovchi stressiga katta ta'sir ko'rsatdi. Bu VVPF ning hujayra redoks holati parametrlarining ko'pini normallashtirish qobiliyatidan aniq xulosaga keldi. Ushbu guruhda ROS, NO, TBARS darajalari va MPO faolligi sezilarli darajada edi (p<0.05)reduced relative="" to="" the="" ccl="" (fig.5a-c)by="" 58.276%,52.519%,68.816%,and="" 62.098%,="" respectively.="" in="" contrast,the="" levels="" of="" tac="" and="" gsh="" and="" the="" activities="" of="" sod="" and="" gpx="" were="" significantly=""><0.05)increased(fig.5a,c,d)by 185.366%,278.584%,48.936%,and="" 332.962%,respectively.concerning="" the="" vvpf="" group,="" the="" tac="" and="" gshlevels,="" along="" with="" the="" sod="" and="" gpx="" activities,="" were="" substantially="" enhanced="" in="" the="" spleens="" of="" rats="" that="" were="" gavage-fed="" vvpf="" for="" ten="" days="" (fig.5a,="" c,="" d)by="" 78.947%,14.803%.32.784%.and="" 14.872%,="" respectively.="" however,="" all="" other="" examined="" oxidative="" stress="" parameters(ros,="" no,="" tbars,="" and="" mpo)were="" non-significantly="" (p'0.05)affected="" in="" the="" spleen="" of="" these="" rats="" by="" 6.274%,6.808%,15.306%,="" and="" 21.574%,="">
Buyrak va o'pka to'qimalarida VVPF ning yallig'lanishga qarshi ta'siri.Shakllardagi grafiklar. 2E, 3E CCl, in'ektsiyadan keyin buyrak va o'pka to'qimalarida yallig'lanishga qarshi vositachilarning massiv ko'tarilishini aniqlaydi. Demak, yadro omili-kappa (NF-K)B, induksiyalanuvchi azot oksidi sintaza (iNOS), siklooksigenaza (COX)-2 va o'simta nekrozi omili (TNF)-a ning katlamli ifodasi buyrakda yuqori tartibga solingan. 505,605 foiz, 960,088 foiz, 2399,110 foiz va 219,150 foiz. Xuddi shunday, o'pka to'qimalarida bu mediatorlarning katlamli ifodasi mos ravishda 628,041 foizga, 755,107 foizga, 4066,674 foizga va 351,253 foizga keskin oshdi. Bundan tashqari, o'pka to'qimalarida interleykin (IL)-1 va IL-8 ning katlama ifodasi mos ravishda 4207,250 foiz va 3307,650 foizga sezilarli darajada oshgan (3E-rasm). Qalamushlarga kelsak, ular zaytun moyi bilan oziqlangan3 hafta (V guruh), buyrakdagi NF-KB, iNOS, COX-2 va TNF-a ning katlam ifodasi nazorat guruhiga nisbatan sezilarli darajada o'zgarmadi (2E-rasm). Xuddi shunday, o'pka to'qimasida IL-1 va IL-8ning katlama ifodasi Cgroup (3E-rasm) bilan bog'liq ravishda sezilarli darajada oshdi. Aksincha, katlama ifodasiO'pka to'qimasida NF-KB(390,183 foiz), iNOS(329,548 foiz), COX-2(286,581 foiz) va TNF- (148,410 foiz) zaytun moyi qo'llanilgandan keyin ko'tarildi (3E-rasm).
![Te improving activity of VVPF to CCl4-induced pulmonary oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8] in the lung tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene](/Content/uploads/2022842169/202203241419113e7b7193a6ea4a74bcf5a1bb106c1d5b.png "Te improving activity of VVPF to CCl4-induced pulmonary oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8] in the lung tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene")
![Te improving activity of VVPF to CCl4-induced brain oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the brain tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene.](/Content/uploads/2022842169/20220324141950426e8d41388b49fbaaa87d6eaf118a73.png "Te improving activity of VVPF to CCl4-induced brain oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the brain tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene.")
![Te improving activity of VVPF to CCl4-induced spleen oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the spleen tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene](/Content/uploads/2022842169/202203241420338bff525bfd98453ba4ab30953eeed168.png "Te improving activity of VVPF to CCl4-induced spleen oxidative stress and necroinfammation. (A) reactive oxygen species (ROS), total antioxidant capacity (TAC), and nitric oxide (NO) levels (B) thiobarbituric acid reactive substances (TBARS) level (C) myeloperoxidase (MPO) and superoxide dismutase (SOD) activities (D) glutathione peroxidase (GPX) activity and reduced glutathione (GSH) level. (E) gene expression fold change of the pro-infammatory mediators [nuclear factor-kappa (NF-κ)B, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α] in the spleen tissues. Results are expressed as mean±S.E of 7 animals. C, Control untreated rats; CCl4, rats with systemic toxicity induced by CCl4 injection (1 mL/kg b.w., IP, 6 times); V, olive oil (vehicle of CCl4)-injected rats (0.5 ml/kg b.w., IP, 6 times); CCl4+VVPF, rats with systemic toxicity afer their gavage-fed VVPF (1.5 g/kg b.w.) for 10 days. VVPF, control rats gavage-fed only VVPF (1.5 g/kg b.w.) for 10 days. Diferent letters indicate the signifcance at p<0.05; CCl4+VVPF group was compared with the CCl4 group, while V and VVPF groups were independently compared with the C group. BHT butylated hydroxytoluene")
VVPF (CCl, plus VVPF guruhi) CCl in'ektsiyasidan so'ng buyrak va o'pkada paydo bo'lgan sinovdan o'tgan yallig'lanishga qarshi vositachilarda katta yaxshilanish ta'siri kuzatildi. NF-KB va TNF-ning katlama ifodasiiNOS, COX-2, IL-1 va IL-8 bilan birga ikkala to'qimalar ham normallashtirildi (2E,3E-rasm). CCl guruhi mos ravishda 78,928 foiz, 64,111 foiz, 66,921 foiz, 69,514 foizni tashkil etdi. O'pka to'qimalarida bu foizlar mos ravishda 79,9158 foiz, 72,199 foiz, 88,049 foiz, 98,082 foiz, 88,{22}} foiz va 97,049 foizni tashkil etgan bo'lsa. Bundan tashqari, buyrakdagi iNOS va COX-2 ning katlamli ifodasi sezilarli darajada edi(p.<0.05)reduced when="" compared="" to="" that="" of="" the="" ccl,="" rats(fig.2e)by="" 66.921%="" and="" 69.514%,="" respectively.="" the="" rats="" in="" the="" vvpf="" group="" showed="" a="" significant=""><0.05) ability="" to="" reduce="" the="" fold="" expression="" of="" the="" pro-inflammatory="" mediators="" in="" the="" kidney="" and="" lung="" tissues="" relative="" to="" the="" control="" group,="" especially="" for="" nf-kb,inos,="" and="" tnf-a.the="" percentages="" of="" reduction="" in="" the="" kidney="" were="" 45.702%,99.993%,and="" 18.134%,respectively,while="" these="" values="" in="" the="" lung="" were="" 90.817%,96.590%,and="" 96.438%,respectively.="" however,="" all="" other="" examined="" pro-inflammatory="" mediators="" either="" in="" the="" kidney(cox-2)="" or="" lung="" (cox-2,il-1β,il-8)were="" non-significantly(p="">0.05) oʻzgargan (mos ravishda 6.109 foiz , 13.468 foiz , 4.691 foiz va 9.194 foiz).
WVPF ning miya va taloq to'qimalariga yallig'lanishga qarshi ta'siri.Buyrak va o'pka to'qimalarida bo'lgani kabi, CCl in'ektsiyasi ham kalamush miyasi va taloq to'qimalarida yallig'lanishga qarshi vositachilarning qatlam ifodasini ko'tarishga olib keldi (Figs.4E,5E). NF-kB, iNOS, COX-2 va TNF-a ning katlam ifodasi miyada mos ravishda 979,924 foiz, 522,286 foiz, 355,513 foiz va taloqda 71,140 foizga sezilarli darajada ko'tarildi. foiz, 1937,934 foiz, mos ravishda, 549,203 foiz va 22,784 foiz. Biroq, faqat 3 hafta davomida zaytun moyi bilan oziqlangan kalamushlar nazorat kalamushlari bilan solishtirganda taloqdagi barcha yallig'lanishga qarshi ko'rsatkichlar uchun normal burmalanish darajasini ko'rsatdi (5E-rasm). Xuddi shu natijalar miya to'qimalarida ham ko'rsatilgan, COX-2 ning sezilarli darajada ko'tarilgan ifodasi bundan mustasno (p).<0.05), relative="" to="" the="" c="" group="" (fig.="" 4e)by="">
CCl dan keyin o'n kun davomida VVPF yuborilgan kalamushlarga kelsak, in'ektsiya (CCl plyus VVPF guruhi), miya va taloqda NF-RB, iNOS, COX-2 va TNF-a ning katlamli ifodalanishining keskin pasayishi. , CCl bilan mast bo'lgan kalamushlarga nisbatan xabar qilingan. Miya to'qimalarida bu qisqarishning foizlari mos ravishda 29,574 foiz, 64,299 foiz, 85,069 foiz va 34,672 foizni tashkil etdi. Taloqda esa bu ko'rsatkichlar 90,772 foiz, 94,888 foiz, 84,006 foiz, 84,2 foizni tashkil etdi. Xuddi shunday NF-KB, iNOS va TNF-a ning miyada (mos ravishda 99,376 foiz 95,678 foiz va 89,976 foiz) va taloqda (69,646 foiz, 92,194 foiz va 79,936 foiz) kalamushdagi katlam ifodasi. VVPF guruhi nazorat guruhiga nisbatan sezilarli darajada kamaydi. O'n kun davomida VVPF qo'llangandan so'ng ikkala to'qimalarda COX{34}} ning burma ifodasi nazoratga nisbatan o'zgarmagan.
Histopatologik topilmalar. Ko'rib chiqilgan to'qimalarning formalin bilan biriktirilgan bo'laklarining fotomikrograflari CCl ning tizimli toksikligini va VVPF ning turli o'rganilayotgan organlarga ta'sirini yaxshilashni ko'rsatdi (6-rasm). Buyrakning nazorat bo'limlari buyrak po'stlog'ini normal buyrak kanalchalari va glomeruli bilan ko'rsatdi. Biroq, CCl bilan 3 hafta davomida in'ektsiya kuchli toksiklikni ko'rsatdi, bu tiqilib qolgan buyrak venasi (CRV (leykotsitlar infiltratsiyasi va buyrak kanalchalari degeneratsiyasi bilan) va epiteliya qatlamini va ularning tipik ko'rinishini yo'qotdi. Bu o'zgarishlar nekroinflamatuar xususiyatlarni aniqladi. VVPF (CCl, plus VVPF) qo'llanilishi buyrakning tipik morfologiyasini saqlab qoldi, faqat tubulalarning ozgina degeneratsiyasi (SDT) Xuddi shunday, zaytun moyi in'ektsiyasi (V guruh) SDTni ko'rsatdi, ammo yo'q. kalamushlarning VVPF guruhining buyrak to'qimalarida morfologik o'zgarishlar aniqlangan.
O'pka to'qimalariga kelsak, nazorat kalamushlari alveolyar qoplar (AS) va alveolyar devorlarning normal morfologiyasini ko'rsatdi. CCl in'ektsiyasidan so'ng uning arxitekturasida jiddiy shikastlanish aniqlandi, bu muntazam alveolyar arxitekturaning yo'qolishi, alveolyar septalarning keng tarqalgan tartibsiz qalinlashishi va alveolyar bo'shliqning qulashi bilan tavsiflanadi. VVPF (CCl, plus VVPF) ni o'n kun davomida yuborish o'pka morfologiyasini tikladi. V guruhidagi kalamushlarning o'pka to'qimalarining bo'laklarida alveolyar havo bo'shliqlarining torayishi bilan ASdagi qalinlik kuzatildi, VVPF guruhidagi kalamushlarda o'pka to'qimalarining morfologiyasi esa g'ayritabiiy xususiyatlarni ko'rsatmadi.
Nazorat qiluvchi kalamushlardagi miya to'qimalari normal neyronlar va glial hujayralar bilan normal tuzilishni ko'rsatdi.CCl bilan in'ektsiya qilinganidan so'ng, bu odatiy arxitektura neyron hujayralarida vakuolalar va piknotik yadrolar bilan og'ir neyron degeneratsiyasiga o'zgartirildi. O'n kun davomida gavaj bilan oziqlangan VVPF CCl ni, toksiklikni engillashtirdi va miya morfologiyasini saqlab qoldi. Bundan tashqari, V va VVPF guruhlari kalamushlari miyaning normal morfologiyasini ko'rsatdi.
Nazorat qiluvchi kalamushlarning taloq to'qimasi yaxshi ajralib turadigan qizil va oq pulpa bo'laklari bilan normal morfologiyani ko'rsatdi. Biroq, CCl bilan mast bo'lgan kalamushlarning taloqi bu hududlarda yallig'lanish hujayralarining haddan tashqari infiltratsiyasiga ega bo'lgan katta zararni aniqladi. Bu zarar VVPF (CCl, plus VVPF) kiritilgandan so'ng yumshatilgan. yallig'lanish hujayralarining kichik oqimi bundan mustasno. Boshqa tomondan, faqat zaytun moyi bilan AOK qilingan kalamushlar (V guruh) noaniq hududlari va ozgina yallig'lanish hujayralarini jalb qilish bilan o'rta darajada uyushmagan oq pulpa hududlariga ega edi. Aksincha, VVPFni o'n kun davomida yuborish (VVPF guruhi) hayvonlarning taloq to'qimalariga salbiy ta'sir ko'rsatmadi va to'qimalar nazorat guruhidagi kabi yaxshi aniqlangan oq va qizil pulpa bo'linmalarini ko'rsatdi.
To'rtta tekshirilgan organda CCl, zarar va VVPF terapevtik ta'sirining ta'siri.CCl ning ta'siri, zararli ta'siri va to'rtta sinovdan o'tgan organdagi VVPF terapevtik ta'siri issiqlik xaritasi chizmalarida baholandi (7-rasm). 7-rasmdagi grafiklar turli o'rganilgan organlarda CCl (CCl, guruh) va VVPF (CCl, plus VVPF guruhi) bilan davolash qilingan kalamushlarda o'rganilgan oksidlovchi stress va nekroinflamasyon parametrlarini to'playdi. Ushbu parametrlarning nazorat (7A, B-rasm) yoki CCl4 (7C, D) guruhlari bilan solishtirganda foiz o'sishi mos ravishda issiqlik xaritasining rangi bilan ifodalangan. Qizil rang parametrning yuqori miqdoriga, ko'k rang esa pastroqqa ishora qildi. Shakl 7A, B ko'rsatadiki, CCl ko'proq oksidlovchi stressni va taloqda (yuqori ROS va past TAC), so'ngra buyrak, miya va nihoyat o'pka to'qimalarida oksidlanish-qaytarilish holatining buzilishini keltirib chiqarishi mumkin. Bundan tashqari, 7B-rasmda ko'rsatilganidek, taloq va miya to'qimalarida NF-KB ning eng yuqori qatlam ifodasi bo'lgan, maqsadli organlardagi boshqa vositachilar esa turli darajadagi burma ifodalariga ega edi.
Boshqa tomondan, Fig.7C, D o'pkada SOD va GPX faolligiga qo'shimcha ravishda TAC va GSH darajasini yaxshilash uchun VVPFning eng yuqori qobiliyatini ko'rsatadi, keyin taloq, buyrak va miya (7C-rasm). Bundan tashqari, bu uzum fraktsiyasi yallig'lanishga qarshi vositachilar darajasini, shuningdek, o'pkada, keyin taloq, buyrak va keyin miyada ROS, NO, TBARS va MPOni yo'q qilishga muvaffaq bo'ldi (7D-rasm). Shunday qilib, issiqlik xaritalari o'pkaning CCl bilan eng kam ta'sirlangan to'qimalari, shikastlanishi va VVPF ning terapevtik qiymatlariga eng sezgir to'qimalar ekanligini ko'rsatdi.
