Part 2: Nephroprotective Nroj Tsuag: Kev Ntsuam Xyuas Ntawm Kev Siv Hauv Cov Kab Mob Ua Ntej thiab Tom Qab Lub Raum

Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com

4. Lub luag haujlwm ntawm cov nroj tsuag hauv lub raum pathophysiology

4.1.Pre-Renal Factors

4.1.1. Mob ntshav qab zib mellitus

Mob ntshav qab zibMob ntshav qab zib mellitus (DM) yog kab mob uas tshwm sim los ntawm hyperglycemia thiab insulin tsis kam. Hauv hom 1 mob ntshav qab zib mellitus, pancreatic p-cells lub luag haujlwm rau kev tsim cov tshuaj insulin raug cuam tshuam thiab ua rau nce qib ntawm cov piam thaj. Hom 2 mob ntshav qab zib mellitus, yog cov lus teb qis ntawm insulin secreted rau cov ntaub so ntswg lub hom phiaj [72,73]. Sij hawm dhau mus, DM yog qhov muaj feem pheej hmoo rau CKD, thiab ntshav qab zib nephropathy yog qhov ua rau muaj qhov kawg.mob raum[45,79]. Cov kab mob pathophysiology ntxias los ntawm DM txhim kho nyob rau hauv cov ntaub ntawv multifactorial thiab tuaj yeem ua rau lwm yam kev pheej hmoo rau lub raum.

Mob ntshav qab zib ua rau glomerular hyperfiltration thiab nce intraglomerular siab vim muaj cov piam thaj ntau kom lim. Cov sodium-glucose thauj cov proteins (SLGT) thiab glucose transporter (GLUT) cov neeg thauj khoom hauv cov tubules sib thooj yuav tsum ua haujlwm ntau dhau, ua rau lub raum hyperperfusion. Cov tubules tsis tuaj yeem tswj cov piam thaj ntau, thiab nws cov zis tawm los ntawm cov zis induces osmotic diuresis. Ntxiv mus, qhov no tuaj yeem ua rau microalbuminuria, macroalbuminuria, nephrotic syndrome, thiab lub raum tsis ua haujlwm, maj mam. Hyperglycemia tseem ua rau lub cev qhuav dej los ntawm kev nce osmotic siab ntawm cov kua dej ntxiv. Yog li ntawd, lub xeev hypovolemic tuaj yeem ncav cuag vim tsis tso zis, vim yog ob peb reabsorptions, thiab intracellular lub cev qhuav dej. Covraum, los ntawm baroreceptors, kuaj pom qhov tsis tshua muaj siab thiab tsis tu ncua ua rau renin-angiotensin-aldosterone system (RAAS), ua rau muaj ntshav siab [80-82]. Ntawm qhov tod tes, insulin tsis kam ua rau mitochondrial superoxide overproduction, activating protein kinase C (PKC) txoj hauv kev ntawm aldose sorbitol tsub zuj zuj thiab tsim cov qib siab glycation kawg-cov khoom (AGEs). Cov hom pa oxygen reactive (ROS) ua rau muaj kev puas tsuaj loj heev los ntawm lipid peroxidation, oxidizing low-density lipoprotein (LDL).ROS kuj tseem ua haujlwm.inflammatory tebactivating lub signaling txoj kev nrog cov transcription yam Bcl2, NF-kB uas txhawb kev qhia ntawm inflammatory cytokines (IL-16, IL-2, IL-6, IL-12 thiab IL -18, TNF-thiab MCP1) thiab apoptosis cascade[45,80]. Thaum kawg, glomerular hypertrophy tshwm sim nrog cov thickening ntawm lub hauv paus membrane thiab mesangial expansion, uas tuaj yeem ua rau glomerulosclerosis, hemodynamic dysregulation, thiab tubulointerstitial fibrosis (Daim duab 2) [45,79].

Nyem qhov no kom paub txog cov organic cistanche

Cocoa hmoov tuaj yeem pab tiv thaiv hyperglycemia los ntawm kev tswj cov piam thaj homeostasis thiab insulin tsis kam. 10 feem pua ​​​​cocoa noj rau Zucker cov rog rog rog tau rov qab los ntawm cov piam thaj thauj khoom (SGLT-2 thiab GLUT-2) thiab tiv thaiv qhov tsis ua haujlwm ntawm glycogenesis tswj GSK-3(glycogen synthase kinase 3) /GS (glycogen synthase) txoj hauv kev thiab phosphorylation (G-6-PASE: qabzib 6 phosphatase). Tsis tas li ntawd, cocoa thim rov qab qhov txo qis ntawm phosphorylated qib ntawm tyrosine-phosphorylated insulin [58]. Aqueous extract ntawm Coffea arabica pulp, nplua nuj nyob rau hauv polyphenols, zoo tiv thaiv hyperglycemia, insulin tsis kam, thiab lipid metabolism. Lub kas fes pulp extract tau nce qib ntawm daim siab antioxidant enzymes catalase (CAT) thiab tooj liab-zinc superoxide dismutase (Cu-Zn SOD), thaiv cov kev ntxhov siab-rhiab qhov taw qhia txoj hauv kev los ntawm kev txo cov theem ntawm p-PKCo / PKCo, thiab txhim kho cationic thauj. Cov txiaj ntsig zoo li no tau pom nrog cov kas fes extract tau tswj hwm raws li cov tshuaj ntxiv ntawm 1000 mg / kg lub cev qhov hnyav (BW) hauv cov qauv ntawm hom 2 mob ntshav qab zib mellitus hauv cov nas, vim yog kev noj zaub mov muaj rog, thiab cov txiaj ntsig tau muab piv nrog metformin raws li kev kho mob ntshav qab zib ( 30 mg / kg BW), thiab ib qho kas fes pulp extract / metformin ua ke kev kho mob (1000/30 mg / kg BW) [59]. Ib yam li ntawd, nyob rau hauv Wistar nas nrog rau lub raum puas los ntawm cov ntshav qab zib thiab cov tshuaj nephrotoxic streptozotocin, kev siv cov nplooj aqueous extract ntawm Anchomanes difformis thim rov qab cov ntaub so ntswg puas ntawm mesangial hlwb, glomerular hypertrophy, thiab membrane puas. Nyob rau theem molecular, cov extract txo cov ntshav concentration ntawm urea, txo oxidative kev nyuaj siab los ntawm kev nce qib ntawm CAT thiab SOD, thiab muaj anti-inflammatory teebmeem los ntawm kev txo cov kev qhia ntawm NF-kB thiab Bdl2, yog li, txo IL {{ 23}}, IL-18, thiab TNF, IL-18 qib. Hauv kev ua haujlwm no, tsis muaj qhov sib txawv tseem ceeb ntawm ob qhov kev sim siab: 200 thiab 400 mg / kg BW, thiab cov nyhuv tsis tshwj xeeb cuam tshuam nrog phytochemicals [45].Tshwj xeeb, cov teebmeem antioxidant zoo sib xws ntawm Hibiscus sabdariffa infusion hauv metabolic syndrome. Cov qauv nas tau raug ntaus nqi rau cov ntsiab lus siab ntawm antioxidants phytochemicals xws li polyphenols, anthocyanins, flavonoids, thiab phenolic acids. Ntxiv nrog rau kev txhim kho antioxidant physiological pathways, phenolic tebchaw koom nrog neutralizing ROS los ntawm pub cov hydrogen atom los yog electron. Cov txiaj ntsig zoo ntawm lub cev hnyav, lipid metabolism, insulin homeostasis, thiab lub raum ua haujlwm tau txais nrog kev kho mob ntawm 2 feem pua ​​​​ntawm H. sabdariffa infusion hauv dej haus [61]. Tsis tas li ntawd, cais flavonoids los ntawm Eysenhardtia polystachya tau sim rau lawv cov tshuaj tiv thaiv kab mob ntshav qab zib thiab nephroprotective teebmeem hauv cov nas mob ntshav qab zib nrog rau lub raum puas tsuaj los ntawm streptozotocin. Cov txiaj ntsig tau tshaj tawm tias 20 mg / kg BW ntawm cov purified extract txo qis oxidative puas nyob rau hauv ob lub raum thiab lub siab, thiab cov nyhuv no tau cuam tshuam rau lub siab antioxidant peev xwm ntawm cov yam ntxwv phytochemicals [60]. Ntxiv nrog rau polyphenols, cov tshuaj tiv thaiv oxidative, thiab txo cov ntshav lipid txawv txav tau pom nyob rau hauv cov kab mob ntshav qab zib Wistar nas kho nrog Agave lechuguilla los ntawm cov khoom rho tawm tau raug ntaus nqi rau cov saponins (triterpenoid glycosides), thiab cov concentration zoo tau tsim los ntawm 300 mg / kg BW [ 83] ib.

Kev siv cov nroj tsuag ua ib qho kev kho mob ntxiv rau ntshav qab zib thiab kev tiv thaiv lub raum yog kev txhawb nqa los ntawm cov kev tshawb fawb soj ntsuam. Ib qho tseem ceeb ntawm cov nroj tsuag los tiv thaiv cov teebmeem ntawm cov kab mob ntshav qab zib mellitus yog lawv cov tshuaj tua kab mob antioxidant thiab tiv thaiv kab mob. Xws li bioactivities tau feem ntau ntaus nqi rau phenolic tebchaw. Txawm li cas los xij, lwm cov phytochemicals kuj tuaj yeem ua lub luag haujlwm rau cov txiaj ntsig tau pom thiab cov kev tshawb fawb ntxiv yuav tsum tau ua kom paub meej lawv cov peev xwm kho tau. Ntawm qhov tod tes, kev tshawb fawb txog koob tshuaj yuav tsum tau ua los tsim cov posology.

4.1.2. Ntshav siab

Ntshav siab yog ib yam kab mob uas tshwm sim los ntawm kev kub siab mus tas li; Raws li thoob ntiaj teb cov lus qhia txog kev kub siab, systolic ntshav siab qhov tseem ceeb yuav tsum siab dua 140 mmHg thiab diastolic ntshav siab siab dua 90 mmHg. Txawm li cas los xij, kev kho tshuaj yog nyob ntawm tus neeg mob lub hnub nyoog thiab kev sib txuam [84-87]. Lub raum muaj cov txheej txheem tswj hwm tus kheej kom ua rau muaj kev hloov pauv hauv cov ntshav siab kom tsis txhob muaj qhov nce hauv intraglomerular siab. Txawm li cas los xij, ntawm cov ntshav siab tas li, cov tshuab rau lub raum tsis ua haujlwm vim tias cov hlab ntsha tuaj tsis muaj zog, tawv, lossis nyias, thiab qhov tshwm sim hu ua myogenic reflex tshwm sim. Thaum lub sij hawm thawj cov lus teb, lub depolarization ntawm daim nyias nyias, los ntawm kev ua kom cov calcium intracellular flux los ntawm L-hom channel, ua rau muaj kev hloov pauv hauv caliber (contraction) hauv afferent arteriole. Thaum cov txheej txheem thawj zaug no ua tsis tiav, muaj qhov nce hauv intraglomerular pom thiab siab, kuj cuam tshuam nrog kev nce hauv sodium chloride load. Txhawm rau kom them nyiaj, lwm txoj kev tswj hwm lub cev hu ua tubuloglomerular tawm tswv yim hloov mus rau, uas tau pom nyob rau hauv cov tubules distal los ntawm macula densa hlwb. Qhov tsis ua hauj lwm hauv cov txheej txheem tswj hwm tus kheej tau xaus rau hauv glomerulonephritis, kev loj hlob ntawm glomerulosclerosis, thiab rupture ntawm lub fenestra, ua rau pom cov molecules loj xws li cov protein, uas ua rau cov proteinuria. Raws li cov protein ntau nyob rau hauv cov tubules, lawv qhib profibrotic, proinflammatory, thiab cytotoxic txoj kev, ua rau tubulointerstitial puas thiab raum caws pliav (Daim duab 3) [88-90].

Hauv cov ntsiab lus no, tincture tau los ntawm cov nroj tsuag herbaceous Cichorium intybus tau pom tias muaj kev cuam tshuam rau cardioprotective thiab nephroprotective hauv cov nas isoprenaline-induced myocardial ischemia qauv. Cov teebmeem kev kho mob tau ua pov thawj los ntawm kev ua kom muaj zog antioxidant thiab tiv thaiv kev ua haujlwm ntawm lub cev thiab txo qis creatinine kinase myocardial band (CK-MB), aspartate aminotransferase (AST), thiab malondialdehyde (MDA) qib. Cov teebmeem zoo li no tau cuam tshuam nrog lub peev xwm antioxidant siab txiav txim siab hauv vitro thiab ntaus nqi rau cov polyphenolic acids thiabflavonoidsquantified nyob rau hauv cov extracts. Cov nyhuv nephroprotective siab dua tau txais nrog 100 mg / mL hauv cov dej haus piv rau qhov qis dua, qhia tias cov concentrations ntau dua tuaj yeem muaj cov teebmeem oxidant thiab inflammatory [62]. Ib yam li ntawd, cov nyhuv anti-hypertensive ntawm polyphenol-nplua nuj H. sabdariffa infusion tau tshwm sim nyob rau hauv tib neeg uas tsis tswj ntshav siab. Cov ntaub ntawv pov thawj tau txais nrog cov koob tshuaj xws li 10, 000 txog 20, 000 mg / d, txawm li cas los xij, cov kws sau ntawv xav tias qhov koob tshuaj qis dua tuaj yeem txaus, txij li 2500 txog 5000 mg / d, thiab tuaj yeem pab txo qis qhov tshwm sim ntawm gastric acidity uas tau pom tias muaj kev phiv tshwm sim nyob rau hauv tsawg heev [46]. Cov txheej txheem ntawm kev tswj ntshav siab tau piav qhia ntxiv nyob rau hauv cov nas muaj ntshav siab thiab Wistar-Kyoto nas ntxiv nrog 360 mg / kg BW ntawm Gardenia jasminoides ethanolic extracts los yog 25 thiab 50mg / kg BW ntawm purified active compounds geniposide (terpenelycoid). Qhov kev ua haujlwm no tau pom tias geniposide txo qis sab laug ventricular kawg-diastolic txoj kab uas hla (LVEDD) thiab sab laug ventricular kawg-systolic txoj kab uas hla (LVESD), thiab txhim kho cov kev ua haujlwm systolic los ntawm kev ua kom sab laug ventricle ejection feem (LVEF) thiab sab laug ventricular fraction shortening (LVFS) . Ntawm qib molecular, kev soj ntsuam ntawm myocardial raug mob biomarkers tau qhia tias kev kho geniposide txhim kho lub plawv ua haujlwm los ntawm kev ua kom lub zog metabolic txoj hauv kev (AMPK / SirT1 / FOXO1), thiab txo tus nqi apoptosis los ntawm kev tswj cov p38 / Bcl2 / BAX txoj kev [63]. Cov teebmeem ntawm G.jasminoides tsuas yog piav qhia qee yam los ntawm kev tua neeg; Yog li, lwm yam bioactive compounds yuav tsum muaj cov txiaj ntsig cardioprotective thiab yuav tsum tau ua tus yam ntxwv. Los ntawm lwm qhov kev xav, cov nyhuv synergic ntawm phytochemicals ntawm cov nroj tsuag rho tawm tuaj yeem ua rau muaj txiaj ntsig zoo.

Cov txiaj ntsig zoo tau txais, tshwj xeeb tshaj yog nyob rau hauv tib neeg kev sim, txhawb kev tshawb fawb ntxiv ntawm cov tshuaj tiv thaiv hypertensive ntawm cov nroj tsuag los txiav txim siab cov koob tshuaj zoo, qhia txog bioactive phytochemicals, ntsuas qhov muaj peev xwm tshwm sim, thiab cuam tshuam txog lawv kev siv nrog cov teebmeem nephroprotective.

4.1.3. Hepatic Injury

Lub siab yog lub luag haujlwm tseem ceeb hauv lub luag haujlwm ntawm metabolizing xenobiotics, thiab cov txheej txheem metabolic xws li hydroxylation, conjugation, acylation, txo, oxidation, sulfonation, thiab glucuronidations [50]. Lub ntsiab ua rau lub siab puas tsuaj yog cov tshuaj uas tsis yog-steroidal anti-inflammatory siv tshuaj, haus cawv, leptospirosis, kab mob, acetaminophen lom, tshuaj tua kab mob, thiab viral hemorrhagic fever [91,92].

Kab mob siab muaj 4 theem sib txawv; Cov theem 1 thiab 2 yog nyob rau theem them nyiaj uas yog asymptomatic, thaum theem 3 thiab 4 yog nyob rau theem decompensatory, tus cwj pwm los ntawm ascites, variceal los ntshav, thiab hepatic encephalopathy, xaus rau theem kawg hauv sepsis thiab lub raum tsis ua haujlwm. Cirrhosis yog tus sawv cev ntawm theem kawg ntawm cov kab mob siab ntev, feem ntau hu ua cirrhosis, tus cwj pwm los ntawm cov nodules regenerative, kev loj hlob fibrosis, thiab cov lus teb mob ntev, ua rau kub siab. Ntau lub tshuab uas ua rau lub raum puas tsuaj, thib ob yog cirrhosis, tau pom. Kev hloov pauv hauv lub siab ua haujlwm raws li qhov tshwm sim ntawm qhov mob ntev thiab kub siab ua rau muaj kev tso tawm ntau dhau ntawm vasodilators xws li carbon monoxide (CO) thiab nitric oxide (NO). Qhov saum toj no txo ​​qis vascular tsis kam ua rau lub plawv tsis ua haujlwm, uas yog pib them nyiaj los ntawm kev nce hauv lub plawv dhia. Raws li tus kab mob loj hlob tuaj, GFR txo qis, ua rau muaj kev ua haujlwm ntawm endogenous vasoconstrictor systems xws li lub paj hlwb sympathetic (SNS), endothelin (ET), arginine vasopressin (AT), RAAS, thromboxane A2 thiab leukotrienes, uas ua rau edema thiab ascites (Daim duab 4).

Thib ob rau saum toj no, muaj qhov nce hauv plab hnyuv permeability, ua rau cov kab mob translocation, kab mob o, thiab oxidative stress [91,93].

Tus qauv ntawm daim siab puas tsuaj los ntawm carbon tetrachloride (CCl) yog tus cwj pwm los ntawm lipid peroxidation thiab MDA tom qab. Tsis tas li ntawd, CCl3O2 · radical cuam tshuam nrog polyunsaturated fatty acids ntawm endoplasmic reticulum uas yog tshwm sim nyob rau hauv siab concentrations ntawm bilirubin, serum glutamic-pyruvic transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT), thiab alkaline phosphatase (alkaline phosphatase). Nyob rau tib lub sijhawm, qhov kev hloov pauv hauv metabolic no ua rau necrosis ntawm daim siab. Hauv CCl4-induced Wistar nas qauv, methanol extract ntawm cov nroj tsuag tshuaj Tinospora crispa tau txo qis qhov siab ntawm tag nrho cov biomarkers thiab txhim kho cov lus teb antioxidant nce qib SOD. Qhov siab tshaj plaws hepatoprotective kev ua haujlwm tau pom ntawm 400 mg / kg BW, uas yog qhov siab tshaj plaws hauv kev sim hauv kev sim. Ntawm cov phytochemicals characterized nyob rau hauv lub extract, lub silico twv ua ntej ntawm kev ua spectra rau cov tshuaj qhia hais tias lub diterpenoid tinocrisposide muaj lub siab tshaj plaws hepatoprotective muaj peev xwm. Txawm li cas los xij, lub khoos phis tawj-pab tshuaj pharmacodynamic tsom tau pom tias qhov sib xyaw no tsis yog ib tus neeg sib tw tshuaj tsim nyog, qhov tseeb, tsuas yog cov flavonoid genkwanin tshwm sim los ua cov tshuaj hepatoprotective ntuj tshuaj. Txoj kev tshawb no qhia txog qhov tsis sib xws ntawm cov cuab yeej kho mob thiab muaj peev xwm toxicity ntawm phytochemicals [50]. Nyob rau hauv tib tus qauv, nonpolar extracts ntawm paj Cirsium vulgare thiab Cirsium ehrenbergi tau pom qhov sib piv hepatoprotective teebmeem nrog ib daim ntawm cov tshuaj tiv thaiv cov pov thawj ntawm 250 thiab 500 mg / kg BW. Lub ntsiab molecule pom nyob rau hauv cov extracts yog lupeol acetate (triterpenoid), yog li lawv xav tias nws yog tus neeg sawv cev tiv thaiv. Txoj kev tshawb no qhia tias lupeol acetate muaj cov tshuaj tua kab mob tiv thaiv kev puas tsuaj los ntawm oxidative kev nyuaj siab; nws inhibits pro-inflammatory enzymes thiab tiv thaiv glycogen depletion [51]. Txawm hais tias cov khoom siv kho mob zoo li no yuav tsum tau lees paub los ntawm kev soj ntsuam cov nyhuv lupeol acetate nyob rau hauv vivo lossis kwv yees nws cov haujlwm los ntawm silico PASS thiab tshuaj tshuaj pharmacodynamic. Lub aqueous-ethanolic extract ntawm cov khoom noj halophyte cog Suaeda vermiculata, nrog cov ntsiab lus siab ntawm antioxidant flavonoids, ua pov thawj los ntes cov dawb radicals tsim los ntawm CCl, cov extract no tau ua tiav qhov txo qis hauv AST thiab ALT, hauv txiv neej Sprague Dawley nas. Ntxiv rau qhov hepatoprotective, nephroprotective, thiab cardioprotective teebmeem tshwm sim ntawm 250 mg / kg BW, kev nyab xeeb ntawm cov extract tau lees paub ntawm 5g / kg BW, thiab IC50 tau tsim los ntawm 56.19 thiab 78.40 ug / mL los ntawm kev soj ntsuam hauv vitro. Tsis tas li ntawd, IC50 ntawm cov tshuaj cytotoxic doxorubicin yog 2.77-fold reversed thaum co-administered nrog S.vermiculata extracts, cov nyhuv no tau txhais tias yog synergetic [52]. Ib yam li ntawd, curcumin hmoov (polyphenol compound tau los ntawm rhizome ntawm Curcuma longa) tiv thaiv lub raum los ntawm kev puas tsuaj los ntawm doxorubicin hauv Wistar nas ntawm 200 mg / kg BW. Kev tshawb fawb biomarkers tau qhia tias curcumin nce antioxidant

Kev ua enzyme (GPx (glutathione peroxidase), CAT, thiab SOD), tiv thaiv lipid peroxidation, txo qhov mob los ntawm kev hloov pauv cytokine qib (TNF-, NF-kB, IL-1, iNOS, thiab COX-2) , thiab txo cov tshuaj lom los ntawm kev txwv kev ua kom apoptosis (caspase 3) [65].

Lwm hom hepatotoxicity yog acetaminophen-induced toxicity (APAP) uas yog los ntawm kev tsim cov reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) los ntawm sulphation thiab glucuronidation metabolic txoj kev. Thaum muaj siab ntau, daim siab GSH yog dhau mus thiab NADQI, uas tsis yog scavenged reacts nrog mitochondrial proteins ntawm hepatocytes. Mitochondrial kev puas tsuaj nce oxidative kev nyuaj siab thiab tom qab ntawd ua rau hepatocyte necrosis [92]. Tsis tas li ntawd, nitric oxide (NO) qib nce nyob rau hauv cov tubules proximal convoluted ntawm lub raum, lub glomerulus, thiab distal convoluted tubules; Qhov no vasodilator hloov lub raum circulatory system. Hauv kev tshawb fawb Swiss albino nas nrog acetaminophen-induced kev puas tsuaj, kev sib koom ua ke ntawm Descurainia Sophia noob extract ntawm 300 mg / kg tau tiv thaiv los ntawm nephrotoxicity. Proximal convoluted tubule qauv tau khaws cia, o, o, thiab necrosis raug txo, thiab txo qis ntawm uric acid, creatinine, thiab ntshav urea nitrogen (BUN) [53].

Hauv lwm tus qauv toxicity, thioacetamide (TAA) rov tsim kho lub siab raug mob thiab cirrhosis zoo ib yam li CCL4 thiab APAPA. Thaum nws yog metabolized, lub siab reactive thioacetamide-S-dioxide yog tsim nrog tom qab nce ntawm oxidative kev nyuaj siab thiab inflammatory cytokines qib [94]. Hauv cov txiv neej Sprague-Dawley nas thioacetamide-induced hepatotoxicity thiab nephrotoxicity tau ntse txo los ntawm ib qho tshuaj ntsuab extract. Cov ntsiab lus siab ntawm cov tshuaj antioxidant polyphenols hauv Euphorbia para las extracts txhim kho cov xwm txheej redox ntawm lub raum cov ntaub so ntswg, txo cov ntshav creatinine, thiab ntshav urea thiab nce qib CAT thiab SOD. Kev tshawb fawb histological tau qhia tias cov extract, tswj hwm ntawm 200 mg / kg lub cev hnyav, tiv thaiv kev puas tsuaj rau nephron ntawm cov hlab ntsha congestion thiab glomerular puas [67].

Hepatotoxicity thiab tom qab nephrotoxicity kuj tuaj yeem tshwm sim los ntawm cov tshuaj uas tsis yog-steroidal anti-inflammatory (NSAID) xws li paracetamol, yog ib qho tshuaj tua kab mob ntau tshaj plaws thoob ntiaj teb. Hauv kev tshawb fawb ntawm tus qauv paracetamol-induced toxicity hauv Wistar nas kho nrog Eurycoma longifolia, kev tiv thaiv tau pom los ntawm kev txo qis ntawm creatinine, urea, albumin, thiab tag nrho cov ntshav cov protein. Ntawm cov ntaub so ntswg, nws ua tiav kev khaws cia ntawm glomeruli, interstitium, thiab tubules hauv ob lub raum. Cov tshuaj ntsuab tshuaj ntsuab tau nthuav tawm cov nyhuv ntawm 200 mg / kg BW, nrog rau kev siv tshuaj raws li pom thaum nce mus txog 400 mg / kg BW [54]. Ib yam li ntawd, cov txiv hmab txiv ntoo mob siab rau (Passiflora spp.) tev extract khaws cov biomarkers ntawm lub raum ua haujlwm xws li urea thiab creatinine ntawm cov qib ib txwm muaj thaum koom nrog paracetamol hauv cov nas albino. Cov kws sau ntawv kuj tseem hais txog qhov kev siv tshuaj nephroprotective los ntawm 150 txog 500 mg / kg BW. Cov nyhuv no tau cuam tshuam nrog lub peev xwm antioxidant ntawm flavonoids thiab tannins ua lub ntsiab phytochemicals pom hauv cov extracts [66].

Thaum cov kab mob ua ntej lub raum mus txog lawv cov theem kawg, kev puas tsuaj yog rov qab tsis tau, thiab yuav tsum tau hloov cov khoom nruab nrog cev. Cyclosporine-A yog siv los ua tshuaj tiv thaiv kab mob txhawm rau txhim kho kev hloov pauv tau zoo, txawm hais tias kev siv tshuaj ntau dhau ntawm cov molecule no ua rau lub cev puas tsuaj. Hauv albino txiv neej Wistar nas nrog Cyclosporine-A-induced nephrotoxicity, nplooj extract ntawm cov nroj tsuag tshuaj Costus tom qab, ntawm 200 mg / kg BW, txo cov ntshav poov tshuaj thiab ntshav urea nitrogen theem, inhibited qhov nce ntawm MDA, nce antioxidant tiv thaiv, thiab tiv thaiv. txhua yam kev hloov pauv (glomerular thiab tubular histology) [69].

Kev raug mob siab feem ntau yog los ntawm kev noj tshuaj lom neeg, thiab hepatotoxicity thiab nephrotoxicity muaj feem xyuam nrog. Kev tiv thaiv ntawm cov khoom cog tau tshaj tawm los ntawm 200 mg / kg BW nrog cov lus teb ntawm koob tshuaj. Xws li kev kho mob muaj peev xwm ntawm cov nroj tsuag, nyob rau hauv ntau cov qauv toxicity thiab ua ke nrog cov tshuaj siv dav, txhawb nqa lawv siv los kho cov kab mob ua ntej lub raum thiab tiv thaiv kev puas tsuaj rau lub raum. Cov haujlwm tau hais tseg tau hais txog cov txheej txheem kev ua haujlwm ntawm cov khoom cog, txawm hais tias, kev tshuaj xyuas ntxiv yog tsim nyog los txheeb xyuas cov txiaj ntsig tau pom zoo nrog phytochemicals, uas tuaj yeem yog los ntawm kev tsom mus rau hauv vivo tsom lossis tshiab hauv silico txoj hauv kev.

4.1.4.Cov tshuaj tua kab mob puas tsuaj

Lwm yam txaus ntshai yog kis kab mob uas tuaj yeem tsim los ntawm ntau cov kab mob resistant; Hauv cov xwm txheej no, kev siv qee yam tshuaj tua kab mob xws li polymyxins thiab colistin yuav tsum raug suav hais tias yog qhov chaw kawg. Nroj tsuag tau dav lees paub tias yog lub hauv paus ntawm cov tshuaj tua kab mob thiab muaj kev txaus siab rau kev ua haujlwm tawm tsam cov kab mob tiv thaiv kab mob. Piv txwv li, crude extracts thiab hnyav feem ntawm nplooj thiab stems ntawm cov nroj tsuag tshuaj Arbutus Bavaria tau raug soj ntsuam ntawm methicillin-resistant Staphylococcus aureus (MRSA) hom. Cov kev ntsuam xyuas hauv vitro tau qhia tias tag nrho cov kev rho tawm thiab cov feem cuam tshuam ua rau cov kab mob bacteriostatic thiab cov kab mob bactericidal. Lub metabolite profiling qhia tias phenolic acids thiab flavonoids, raws li lub ntsiab phytochemicals nyob rau hauv cov extracts thiab feem, yog lub luag hauj lwm rau cov antibacterial kev ua si [55]. Antimicrobial thaj chaw ntawm cov nroj tsuag tau dav tshaj tawm. Txawm li cas los xij, feem ntau ntawm txoj kev tshawb no yog ua nyob rau hauv vitro, thiab cov txiaj ntsig yuav tsum tau lees paub los ntawm kev soj ntsuam hauv vivo ntxiv kom pom zoo rau lawv siv hauv kev kho cov kab mob sib kis. Qhov ntawd tuaj yeem piav qhia vim li cas cov tshuaj tua kab mob tseem siv ntau.

Cov tshuaj tua kab mob tuaj yeem ua rau hepatotoxicity thiab nephrotoxicity. Cov nyhuv tshuaj lom yog tsim los ntawm kev thauj mus los hauv daim nyias nyias ntawm lub tubule proximal; nyob rau ntawm ntug ntawm txhuam, muaj cov nqi tsis zoo thiab cov tshuaj tua kab mob no muaj lub nplhaib polycationic hauv lawv cov qauv, rau kev rov ua dua tshiab thiab kev puas tsuaj ntawm tes. Tsis tas li ntawd, nws txhawb nqa cov roj cholesterol biosynthesis thiab nce qib cholesterol hauv cov zis. Lub nephrotoxicity ntawm gentamicin ua raws li ib qho kev thauj mus los hauv tib cheeb tsam ntawm cov tubule ze ze, tom qab internalization los ntawm endocytosis, rupture nyob rau hauv lub cell, tso tawm ntawm proteases, thiab kev puas tsuaj rau lub organelles, tiam ntawm ROS, xaus nyob rau hauv necrosis [56,95]. Qee cov tshuaj tua kab mob tuaj yeem ua rau AKI los ntawm kev raug mob mitochondrial nrog rau kev tsim ROS tom qab thiab kev hloov pauv hauv txoj kev siv hluav taws xob metabolic, kev hloov pauv hauv lub raum ntawm qib micro thiab macro, thiab cov ntaub so ntswg puas tsuaj [13]. Kev siv tshuaj tua kab mob yog qhov tseem ceeb hauv lub neej niaj hnub los tiv thaiv kev kis kab mob, uas, yog tias tsis kho, tuaj yeem ua rau sepsis poob siab; ntawm no nws tuaj yeem pom tias kev sib ntaus cov kab mob no nrog tshuaj tua kab mob kuj ua rau hepatotoxicity thiab nephrotoxicity. Hauv vivo, cov nroj tsuag tau ua pov thawj tias lawv muaj peev xwm rov qab ua cov tshuaj tua kab mob hauv lub siab thiab raum cov ntaub so ntswg. Hauv Wistar nas kho nrog gentamicin thiab Atlas mastic tsob ntoo (Pistacia Atlantica), nplooj extracts ib txhij pom cov tshuaj tiv thaiv kab mob qis qis nrog cov lus teb ntawm koob tshuaj uas muaj pov thawj ntawm 200 thiab 800 mg / kg lub cev hnyav. Cov nyhuv tiv thaiv tau raug ntaus nqi rau cov tshuaj tua kab mob antioxidant thiab tiv thaiv kev mob ntawm phenolic acids thiab flavonoids. Qhov txo qis ntawm qhov mob yog ua pov thawj los ntawm kev txo qis hauv cov ntshav lipid profile thiab nce qib siab lipoproteins ntau (HDL). Kev tiv thaiv kev tiv thaiv oxidative puas tsuaj tau tshwm sim hauv kev txo qis ntawm MDA prevalence los ntawm kev ua kom cov ntshav plasma antioxidant muaj peev xwm nrog kev ua haujlwm siab dua ntawm CAT thiab SOD thiab ntau dua vitamin C qib [68]. Ib yam li ntawd, hauv tib tus qauv gentamicin-induced nephropathy, nplooj extract ntawm Punica granatum (pomegranate) txo cov ntshav creatinine, urea, thiab albumin thiab cov zis albumin. Tsis tas li ntawd, cov extract no tshem tawm hydroxyl radicals thiab singlet oxygen, nce tus naj npawb ntawm cov antioxidant enzymes xws li CAT, SOD, thiab GSH, txo MDA thiab qhia txog TNF-, thiab thaum kawg, hauv cov ntaub so ntswg nws txhim kho morphological alterations xws li tubular atrophy, necrosis, vascularization thiab congestion ntawm peritubular cov hlab ntsha. Cov nyhuv no tau tshwm sim ntawm 200 thiab 400 mg / kg BW, whereas ntawm 100mg / kg BW, tsis tiav nephroprotection tau |56]. Nyob rau hauv sib piv, 100 mg / kg BW ntawm pomegranate txiv hmab txiv ntoo tev extract tau pom zoo hepatoprotective thiab nephroprotective zog nyob rau hauv kev kho mob nrog high koob tshuaj ntawm cov tshuaj tua kab mob vancomycin, thiab kev tiv thaiv zoo dua yog highlighted thaum noj ua ntej kev kho mob vancomycin 57]. Cov txiaj ntsig no qhia tias muaj cov nyhuv antagonist ntawm cov tshuaj tua kab mob thiab cov nroj tsuag extract.

Yog li, cov nroj tsuag thiab lawv qhov sib txawv tuaj yeem siv los thim rov qab tshuaj tua kab mob toxicity tsis yog nyob rau hauv lub raum tab sis kuj nyob rau hauv daim siab thiab plab, tshwj xeeb tshaj yog ua raws li antioxidants thiab anti-inflammatory. Lub tswv yim rau kev kho mob ntxiv xws li hom kev tswj hwm thiab koob tshuaj yuav tsum tau kawm ntxiv kom lav qhov kev kho mob ntawm cov khoom cog thiab tshuaj tua kab mob.

4.1.5 ib. Lub plab Microbiota

Cov kev tshawb fawb hauv plab hnyuv microbiota tau txais qhov tseem ceeb vim nws tau raug pov thawj tias nws qhov kev hloov pauv ua rau kev tsim cov uremic retention solutes (URS) thiab muaj feem cuam tshuam ncaj qha rau kev tsis zoo ntawm lub raum ua haujlwm.Ib qho ntawm cov tshuaj lom metabolites yog trimethylamine N-Oxide (TMAO) . Lub TMA molecule yog tsim los ntawm microbiota los ntawm nws cov khoom noj khoom haus precursors xws li carnitine, choline, thiab betaine tau txais los ntawm cov tsiaj protein ntau. Tom qab ntawd, nyob rau hauv daim siab, nws yog oxidized ua tsaug rau monooxygenase, tso tawm mus rau hauv kev, thiab mus txog rau lub raum, nyob rau hauv cov ntaub ntawv no, lub raum yuav tsum tau ua hauj lwm rau excrete metabolite. TMAO tsub kom endogenous o, txhawb atherogenesis, thiab modulates lipid metabolism. Nws tau raug pom nyob rau hauv vivo cov kev tshawb fawb thiab kev sim tshuaj uas tau txais cov zaub protein txo cov TMAOlevels [96,97], txhawb kev noj qab haus huv ntawm cov nroj tsuag thiab kev siv cov nroj tsuag tshuaj los kho cov kab mob ua ntej lub raum.

Antidiabetics, tshuaj tua kab mob, analgesics thiab antipyretics, thiab lwm yam tshuaj, ntxiv rau ua rau lub siab thiab lub raum puas, kuj yog lub luag hauj lwm rau kev hloov nyob rau hauv lub plab hnyuv microbiota, ua rau raws plab, thiab lwm yam physiological kab mob. Hauv kev mob raws plab, qhov txo qis hauv probiotics cuam tshuam thiab muaj kev loj hlob ntawm cov kab mob kis tau zoo. Ib qho ntawm feem ntau siv cov nroj tsuag raws li kev kho tshuaj ntxiv yog raws li prebiotics. Ntau cov phytochemicals twb tau ua pov thawj los ua qhov zoo ntawm cov plab hnyuv microbiota, txhim kho probiotics kev loj hlob thiab txo cov kab mob kev loj hlob. Ntawm lawv, polyphenol resveratrol yog ib qho kev sib xyaw ua ke los ntawm ntau hom nroj tsuag. Vim nws tsis tshua muaj bioavailability, nws tsis yog ntxov metabolized yog li mus rau txoj hnyuv thiab inter-acts nrog lub plab microbiota, hloov cov muaj pes tsawg leeg ntawm microbial zej zog. Los ntawm kev hloov cov microbiota, nruj junctions tuaj yeem nce ntxiv los ua ib qho kev thaiv uas tiv thaiv cov kab mob metabolic tsis zoo los ntawm kev hla thiab tuaj txog ntawm daim siab; qhov kev sib tshuam no yog hu ua lub plab-siab axis. Resveratrol (50 mg / kg BW) kho cov kev sib tshuam nruj hauv cov kab mob uas tsis muaj cawv muaj roj hauv lub siab uas tshwm sim los ntawm kev noj zaub mov muaj roj ntau hauv C57BL / 6J nas qauv. Nws kuj tau nce Olsenella thiab Allocaculu genus, uas qhia txog kev hloov pauv tau zoo rau tus kab mob [98]. Hauv C57BL / 6 nas qauv nrog lincomycin hydrochloride-vim raws plab, ntau yam tshuaj ntsuab residues (Dioscorea opposite rhizome, Pseudostellaria heterophylla cag tuber, Crataegus pinnatifida txiv hmab txiv ntoo, Citrus reticulata pericarp, thiab Hordeum subfermentistilacilli pericarp txiv hmab txiv ntoo) thiab Lactobacillus Plantarum M3) tau sim rau lawv cov txiaj ntsig zoo ntawm plab microbiota. Lub fermentation supernatant ho inhibited raws plab tshwm sim los ntawm cov tshuaj tua kab mob, txhim kho cov kab mob ntau haiv neeg, thiab restore Lactobacillus johnsoni dominance nyob rau hauv lub plab microbial zej zog. Tsis tas li ntawd, cov tshuaj tua kab mob antioxidant thiab tshuaj tua kab mob tau pom hauv vitro [99]. Hauv kev ua haujlwm kawg no, cov kws sau ntawv txhawb kom siv cov tshuaj ntsuab uas muaj nyob hauv yav dhau los ua tiav los ntawm cov tuam txhab muag tshuaj kom tau txais cov khoom kho tshiab. Qhov no qhia tau hais tias lub peev xwm ntawm cov nroj tsuag hauv pharmacology yog deb ntawm kev siv tag nrho.

4.1.6. Rhabdomyolysis

Rhabdomyolysis yog ib qho mob uas tshwm sim los ntawm cov leeg nqaij sarcolemma. Ob txoj hauv kev tau raug txheeb xyuas, ua tsis tiav hauv kev tsim hluav taws xob los ntawm sodium-potassium AT-Pase thiab calcium ATPase twj, thiab ua kom cov calcium-dependent phospho-lipases thiab proteases los ntawm kev nce hauv calcium intracellular. Cov enzymes no rhuav tshem daim nyias nyias thiab cytoskeleton proteins ua rau necrosis. Vim yog necrosis, electrolytes thiab intracellular proteins xws li myoglobin, creatine kinase, lactate dehydrogenase, aspartate transaminase, thiab aldose raug tso tawm mus rau hauv lub cev circulation Rhabdomyolysis syndrome yog tshwm sim los ntawm metabolic, noob caj noob ces, structural, inflammatory, thiab / los yog traumatic ua. Crush Syndrome, cov leeg nqaij hypoxia, kev tawm dag zog hnyav, kev tsis haum xeeb ntawm caj ces, kev siv tshuaj thiab / lossis tshuaj noj [100,101]. Ntxiv nrog rau cov xwm txheej no, muaj kev koom tes nrog cov tshuaj tua kab mob xws li cefditoren, daptomycin, cefaclor, norfloxacin, erythromycin, clarithromycin, azithromycin, meropenem, cefdinir, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, linezooxin2.

Lub rhabdomyolysis tom qab ua rau lub raum puas los ntawm kev ua kom cov platelets thiab heme pawg (cov khoom ntawm cov leeg nqaij necrosis); pawg no cuam tshuam nrog macrophage antigen 1 (Mac-1) thiab txhawb nqa citrullination ntawm histones, ROS ntau lawm, thiab tom qab macrophage extracellular trap (MET) tsim. Kev puas tsuaj rau lub raum tshwm sim los ntawm kev puas tsuaj rau cov hlwb ntawm cov kab mob sib kis vim yog qhov sib txuam ntawm ROS, lipid peroxidation, thiab nag lossis daus ntawm myoglobin nrog uromodulin (Daim duab 5) [100,103].

Vim tias tus kab mob no yuav tsum tau kho kom zoo, nws yog ib qho tseem ceeb uas yuav tau saib xyuas lub raum ntxiv, kom tsis txhob muaj kev phiv los ntawm cov tshuaj. Piv txwv li, qee cov tshuaj ntsuab (Pteridium sp.) tau raug tshawb xyuas los ua lub luag haujlwm rau rhabdomyolysis thiab ntau lub cev tsis ua haujlwm hauv cov neeg mob uas tsis muaj keeb kwm kho mob tshwj xeeb thiab ib qho uas muaj ntshav siab. Cov nroj tsuag no muaj flavonoids, mob plawvglycosides, saponins, thiabphenols; Txawm li cas los xij, qhov toxicity tsis tuaj yeem raug ntaus nqi rau ib qho phytochemical tshwj xeeb [104]. Nyob rau hauv sib piv, cov teebmeem exerted los ntawm curcumin tau nthuav tawm raws li ib qho kev cog lus rau kev tswj ntawm rhabdomyolysis. Hauv glycerol-induced rhabdomyolysis qauv ntawm C57BL / 6J nas, curcumin txo ROS ntau lawm los ntawm kev ua kom Nrf2 / HO-1 axis, thim rov qab qhov txo qis ntawm lub raum GSHlevels, thiab txo qhov ua kom NF-KB thiab ERK pro. - inflammatory kab mob. Ntxiv mus, histopathology tau qhia tias curcumin txhim kho tubular cell tuag thiab lumen dilatation, interstitial edema, thiab poob ntawm txhuam ciam teb. Cov teebmeem no tau txais kev siv 1000 mg / kg BW ntawm curcumin raws li kev tiv thaiv kev kho mob thiab tom qab rhabdomyolysis induction. Tsis tas li ntawd, HO-1 tau raug txheeb xyuas tias yog txoj hauv kev tseem ceeb cuam tshuam nrog cov nyhuv nephroprotective ntawm curcumin [64]. Kev siv cov nroj tsuag los tiv thaiv lub raum raug mob yuav tsum tau saib xyuas tshwj xeeb thaum lub raum ua ntej yog rhabdomyolysis vim muaj qhov cuam tshuam tsis zoo ntawm qee cov nroj tsuag phytochemicals. Nyob rau hauv cov ntsiab lus no, purified extracts thiab cov tebchaw yuav tsum nyiam dua li complex extracts kom tsis txhob muaj kev cuam tshuam tsis zoo thiab muab ib qho kev kho mob.