Lub raum-tiv thaiv lub luag haujlwm ntawm lipoic acid hauv raum kab mob
Aug 31, 2023
Abstract:Lub raum yog ib qho tseem ceeb hauv lub cev uas tshem tawm cov khoom pov tseg hauv metabolic thiab reabsorbs cov khoom noj muaj txiaj ntsig. Nws kuj koom nrog hauv kev tswj cov ntshav siab, kev saib xyuas ntawm electrolyte tshuav thiab ntshav pH homeostasis, nrog rau erythropoiesis thiab vitamin D maturation. Vim muaj kev ua haujlwm hnyav, lub raum yog lub cev xav tau lub zog thiab raug cuam tshuam los ntawm endogenous thiab exogenous insults, ua rau kev loj hlob ntawm ob qho tib si.mob raum raug mob(AKI) lubmob raum mob(CKD). Txawm li cas los xij, tsis muaj kev tswj xyuas kev kho mob los kho AKI lossis CKD kom zoo. Yog li ntawd, cov kev kho tshiab tshiab rau kev tawm tsam raum raug mob yog qhov xav tau sai. Tsab ntawv tshuaj xyuas no tham txog lub luag haujlwm ntawm -lipoic acid (ALA) hauv kev tiv thaiv thiab kho mob raum. Peb tsom mus rau ntau yam tsiaj ua qauv ntawm lub raum raug mob los ntawm cov txheej txheem renoprotective ntawm ALA tau raug tshem tawm. Cov tsiaj ua qauv suav nrog ntshav qab zib nephropathy, sepsis-induced raum raug mob, raum ischemic raug mob, unilateral ureteral obstruction, thiab raum raug mob los ntawm folic acid thiab hlau xws li cisplatin, cadmium, thiab hlau. Peb qhia txog cov txheej txheem ntawm ALA lub raum tiv thaiv kev ua haujlwm uas suav nrog txo qis oxidative puas tsuaj, ua kom muaj peev xwm antioxidant, tiv thaiv kev mob, txo lub raum fibrosis, thiab txo qis nephron cell tuag. Nws yog los ntawm cov txheej txheem no uas ALA ua tiav nws cov kev ua haujlwm lom neeg ntawm kev ua kom lub raum raug mob thiab txhim kho lub raum ua haujlwm. Txawm li cas los xij, peb kuj tau taw qhia tias yuav tsum muaj kev tshawb fawb ntau dua, preclinical, thiab kev kho mob yuav tsum ua kom ALA ua tus kws kho mob zoo dua rau kev tsom mus rau lub raum tsis zoo.
Cov ntsiab lus: lipoic acid;mob raum raug mob; mob raum mob; mob ntshav qab zib raum; ntshav qab zib nephropathy; nephroprotection
Nyem qhov no kom tau txais CISTANCHE rau CKD kev kho mob
1. Taw qhia
Lub raum yog ib qho tseem ceeb hauv nruab nrog cev, koom tes hauv kev saib xyuas ntawm electrolyte tshuav, ntshav pH ruaj khov, tshem tawm cov metabolism hauv cov khib nyiab, thiab rov qab nqus cov as-ham thiab cov zaub mov [1,2]. Lub raum tseem koom nrog hauv erythropoiesis, vitamin D maturation, thiab kev tswj ntshav siab [3]. Nyob rau hauv cov kab mob pathophysiological xws li kev yoo mov, kev tshaib kev nqhis ntev, thiab insulin tsis kam, lub raum kuj tuaj yeem tsim cov piam thaj los ntawm gluconeogenesis siv cov khoom ua ntej xws li glycerol, alanine, pyruvate, thiab lactate [4]. Yog li ntawd, lub raum ib txwm muaj kev ua haujlwm hnyav thiab yog li raug rau ntau yam txaus ntshai uas tuaj yeem ua rau mob raum lossis raug mob. Muaj ob hom kab mob raum: mob raum mob (CKD) [5] thiab mob raum mob (AKI) [6]. CKD tshwm sim thaum muaj qhov txo qis hauv lub raum ua haujlwm ntau dua 3 lub hlis vim kev puas tsuaj rau glomerular pom thiab raug mob tubular [7]. Nws tau raug kwv yees tias los ntawm 2040, CKD yuav dhau los ua qhov thib tsib ua rau tuag thoob ntiaj teb [8]. Ntawm qhov tod tes, AKI tshwm sim thaum muaj qhov txo qis hauv lub raum ua haujlwm tsawg dua 3 lub hlis, thiab qhov no tau qhia los ntawm acidosis, kua dej ntau dhau, thiab qhov txawv txav nrog electrolytes thiab hematology hloov [7]. Nws kuj tseem paub tias cov tib neeg uas muaj CKD tuaj yeem muaj kev pheej hmoo siab ntawm AKI [8]. Tam sim no, tsis muaj cov khoom lag luam los kho AKI lossis CKD. Thaum lub raum lim ntshav feem ntau siv los tiv thaiv kev puas tsuaj ntxiv rau lub raum thiab tswj lawv txoj haujlwm, kev hloov lub raum yuav yog qhov chaw kawg rau cov neeg mob muaj sia nyob. Yog li, yog tias tswj tsis tau, AKI thiab CKD tuaj yeem ua rau lub raum tsis ua haujlwm, uas ua rau muaj kev mob tshwm sim thiab kev tuag [7,9]. Yog li ntawd, muaj ib qho kev xav tau ntawm kev sib ntaus sib tua raum.
Txhawm rau tiv thaiv kab mob raum, ntau txoj kev kho mob tau tshawb pom [10–13]. Cov no muaj xws li exogenous thiab endogenous tebchaw, kev noj haus manipulations, modulation ntawm metabolic pathways, qia cell mus kom ze, thiab cell signaling txheej txheem [10,11,14–21]. Hauv tsab xov xwm no, peb yuav tsom mus rau lub luag haujlwm ntawm lipoic acid hauv kev tiv thaiv thiab ua kom lub raum raug mob. Tshwj xeeb, peb yuav tsom mus rau cov kev tshawb fawb siv cov qauv tsiaj los tshawb txog kev tiv thaiv ntawm lipoic acid ntawm lub raum raug mob. Cov tsiaj qauv ntawm lub raum raug mob muaj xws li mob ntshav qab zib raum lossis mob ntshav qab zib nephropathy, lub raum ischemia-reperfusion raug mob, sepsis-induced raum raug mob, unilateral ureteral obstruction (UUO)-induced raum raug mob, cisplatin-induced raum raug mob, cadmium-induced raum raug mob, folicacid-induced raum raug mob, thiabhlau-induced mob raum raug mob(Daim duab 1).
Daim duab 1. Cov qauv tsiaj ntawm lub raum raug mob tau tham hauv kab lus no. Cov qauv no muaj xws li mob raum raug mob thiab mob raum mob.
2. Alpha-Lipoic Acid
ALA yog ib txwm tshwm sim dithiol compound [22]. Nws yog ib qho cofactor rau -ketoglutarate dehydrogenase, branched-chain amino acid dehydrogenase, thiab pyruvate dehydrogenase [23–25] (Daim duab 2). Yog li, ALA yog lub zog hloov pauv [26,27] (Daim duab 3). Ntxiv mus, vim nws muaj peev xwm sib pauv thiol pawg nrog lwm cov thiol-muaj cov molecules, xws li glutathione thiab protein cov cysteine residues, ALA tseem hu ua redox modulator [26–28] (Daim duab 3). ALA feem ntau hu ua universal antioxidant vim tias nws tuaj yeem ua antioxidant hauv ob qho tib si lipophilic thiab hydrophilic nqis los txo cov khoom ntawm oxidative metabolism, xws li reactive oxygen hom (ROS) thiab reactive nitrogen hom (RNS) (Daim duab 4) [29 ]. ALA tseem tuaj yeem chelate hlau xws li zinc, hlau, thiab tooj liab thiab rov tsim cov tshuaj tua kab mob endogenous-xws li glutathione-thiab exogenous vitamin antioxidants-xws li cov vitamins C thiab E-nrog cov kev mob tshwm sim tsawg [30] (Daim duab 4). Qhov tseem ceeb tshaj, ALA tseem tuaj yeem cuam tshuam kev mob tshwm sim los ntawm kev tsom NF-KB thiab txo qis kev tso tawm ntawm cov kab mob cytokines (Daim duab 4). Yog li ntawd, nws tau raug pom tias los ntawm kev tshem tawm cov pa dawb radicals, ALA tuaj yeem ua rau glomerular muaj nuj nqi thiab txo qis raum mob [31]. Cov kev tshawb fawb kuj tau pom tias kev kho mob nrog ALA tuaj yeem txo cov mob raum raug mob los ntawm kev txo cov ntshav urea nitrogen,creatinine theem qog necrosisfactor-alpha (TNF- ), interleukin -6 (IL-6), thiab interleukin -1 beta (IL-1 ), yog litxo endothelin-1vasoconstriction, neutrophil diffusion, thiab mob hauv lub raum.
Daim duab 2. Lipoic acid yog cofactor ntawm mitochondrial 2-ketoacid dehydrogenase complex, nrog rau cov pyruvate dehydrogenase complex, -ketoglutarate dehydrogenase complex, thiab branched-chain amino acid dehydrogenase complex. E1 subunit yog 2-ketoacid decarboxylase siv TPP ua cofactor; E2 subunit yog dihydrolipoamide acyltransferase siv lipoic acid ua cofactor; E3 subunit yog dihydrolipoamide dehydrogenase, uas siv NAD + ua tus txais hluav taws xob rau oxidation ntawm lipoyl pawg txuas rau E2 subunit. E3 catalyzes tsim cov oxidized daim ntawv ntawm lipoic acid thiab generates NADH nyob rau hauv lub meantime [32-34].
Daim duab 3. Lipoic acid yog koom nrog thiol-disulfide exchanges uas hloov kho lub cell lub redox thiab lub zog raws li txoj cai.
Daim duab 4. Kev ua lom neeg ntawm lipoic acid thiab nws cov txheej txheem muaj peev xwm, uas suav nrog kev rov tsim dua tshiab ntawm glutathione, vitamins C thiab E, tshem tawm ROS, chelating hlau ions, thiab lub zog tiv thaiv kab mob.
3. Lub luag haujlwm tiv thaiv ntawm -Lipoic Acid (ALA) hauv raum raug mob
Cov kab mob hauv lub raum tuaj yeem tshwm sim los ntawm ntau qhov kev thuam, xws li ntshav qab zib, ischemic reperfusion, tshuaj toxicity, sib piv xov xwm, thiab tshuaj noj [7]. Yog tias tsis tswj hwm, AKI tuaj yeem ua rau lub raum tsis ua haujlwm nrog 20% kev tuag [25]. AKI yog tus cwj pwm los ntawm kev nce hauv cov ntshav creatinine, oliguria, thiab muaj cov cim kev puas tsuaj rau lub raum xws li albuminuria, electrolyte abnormalities vim tubular teeb meem, los yog cov qauv kev puas tsuaj pom nyob rau hauv imaging los yog histology [9]. ALA prophylaxis tau pom tias txo qis raum tubular raug mob cov qhab nia, cov cim kev puas tsuaj rau cov zis, cov ntshav creatinine kev puas tsuaj, thiab nce glomerular pom [35]. Hauv cov tshooj hauv qab no, peb yuav tham txog cov teebmeem nephroprotective thiab cov txheej txheem tiv thaiv ntawm ALA hauv ntau hom tsiaj ntawm lub raum raug mob, raws li qhia hauv daim duab 1
3.1. Mob ntshav qab zib nephropathy
Mob ntshav qab zib nephropathy (DN), tseem hu ua mob ntshav qab zib raum (DKD) [36–38], yog qhov ua rau CKD thiab lub raum tsis ua haujlwm kawg hauv cov neeg mob ntshav qab zib [39–41]. Nws tau raug tsim zoo tias mitochondrial dysfunction ua rau DKD, thiab mitochondrion yog lub hom phiaj rau kev sib ntaus DKD [42–44]. DN tuaj yeem suav tias yog qhov teeb meem microvascular los ntawm hom 1 lossis hom 2 mob ntshav qab zib mellitus [7,41]. Cov kab mob ntshav qab zib hauv lub raum no yog tus cwj pwm los ntawm kev txo qis hauv glomerular pom, proteinuria, thiab lub raum fibrosis [7]. Hyperglycemia tsub kom oxidative kev nyuaj siab, ua rau lub overproduction ntawm reactive oxygen hom (ROS) [45] thiab dysregulation ntawm glutathione metabolic txoj kev [7]. Malondialdehyde (MDA) yog cov khoom kawg ntawm lipid peroxidation thiab tau nquag siv los ua tus cim zoo ntawm cov dawb radicals thiab oxidative stress [46–49]. Cov kev tshawb fawb tau pom tias kev kho ua ntej nrog ALA txo MDA cov ntsiab lus thiab ameliorated raum oxidative kev nyuaj siab [32,50]. Lipoamide, derivative ntawm ALA, tau ua pov thawj los tiv thaiv lub raum fibrosis hauv ntshav qab zib los ntawm kev txhim kho mitochondrial muaj nuj nqi thiab tswj cov kev qhia ntawm kev ua kom cov transcriptional factor retinal X receptor alpha [51]. Hauv cov qauv nas ntawm cov ntshav qab zib uas tshwm sim los ntawm nicotinamide ua ke nrog streptozotocin, siv sij hawm tsawg dua hauv kev tsim cov nas cov qauv ntshav qab zib [52], Dugbartey li al. kuj tau ua pov thawj tias ALA lub raum tiv thaiv mechanism muaj kev ua kom lub raum cystathionine -lyase / hydrogen sulfide system [53]. Nws kuj tau pom tias ALA muaj kev sib koom ua ke ntawm kev txo qis hauv cov ntshav cytokines thiab txhim kho lub raum kev ua haujlwm hauv cov neeg mob ntshav qab zib thaum ua ke nrog angiotensin II receptor inhibitor valsartan [54]. Daim duab 5 qhia txog cov pov thawj txaus ntseeg ntawm histological staining uas ALA nthuav tawm muaj zog tiv thaiv kab mob raum mob ntshav qab zib hauv hom 2 mob ntshav qab zib hom tsiaj [55] mechanism ntawm ALA's nephroprotection hauv ntshav qab zib yog nws lub peev xwm los qhib Nrf2 teeb liab txoj hauv kev, ua rau kev txhim kho ntawm qhov thib ob- theem cytoprotective proteins xws li heme oxygenase-1 (HO-1) thiab NAD(P)H quinone dehydrogenase 1 (NQO1) [56–58]. Nws yuav tsum tau taw qhia tias thaum ALA yog nephroprotective nyob rau hauv cov kab mob ntshav qab zib mellitus, nws tuaj yeem ua rau cov tshuaj tiv thaiv oxidant lossis tshuaj lom thiab tuaj yeem ua tsis tau raws li Nrf2 inducer nyob rau hauv qee yam kab mob pathophysiological [59–61]. Tsis tas li ntawd, thaum ALA tau xav tias yuav ua kom cov insulin taw qhia txoj hauv kev los tiv thaiv ntshav qab zib [28] thiab tau pom tias tiv thaiv kom tsis txhob muaj fructose-induced cardiometabolic ntshawv siab thiab lub raum tsis ua haujlwm [62], nws kuj tau tshaj tawm tias ALA tsuas tuaj yeem txo cov proteinuria thiab oxidative. kev ntxhov siab yam tsis ua kom qeeb ntawm kev mob ntshav qab zib raum tsis ua haujlwm [63].
3.2. Sepsis-Induced raum Injury
Sepsis yog qhov muaj peev xwm ua rau muaj kev phom sij rau lub neej vim muaj kev cuam tshuam ntau dhau rau cov kab mob kab mob [64–66]. Mob hnyav sepsis tuaj yeem ua rau ntau lub cev tsis ua haujlwm, nrog rau lub raum yog lub cev cuam tshuam tshaj plaws [67,68]. Nws tau kwv yees tias ze li ntawm 50% ntawm cov neeg mob septic yuav tsim mob raum raug mob, thiab tsis muaj kev kho mob zoo rau septic AKI [69]. Hauv qhov no, ntau tus neeg tshawb xyuas tau soj ntsuam tag nrho ALA qhov kev tiv thaiv thiab kho qhov tseem ceeb hauv sepsis-induced AKI qauv los ntawm kev txhaj tshuaj lipopolysaccharides, txawm tias cacal puncture thiab ligation (CPL)- induced septic AKI tau siv qee zaus [22,70]. Nws tau raug pom tias ALA tuaj yeem tiv thaiv kab mob raum raug mob los ntawm kev txhim kho autophagy [71]. Tsis tas li ntawd, ALA kuj tseem tuaj yeem ua rau mob sepsis-induced AKI los ntawm kev tiv thaiv kab mob los ntawm inhibition ntawm NF-KB signaling pathway [72], attenuating mitochondrial oxidative stress, thiab khaws cia hom 3 Na + / H + exchanger thiab aquaporin 2 qhia hauv lub raum [73] . ALA tseem tuaj yeem cuam tshuam qhov kev tso tawm ntawm qog necrosis factor- , interleukin (IL) -6, thiab IL-1 rau hauv cov ntshav thiab inhibit qhov kev qhia ntawm inducible nitric oxide synthase [22] hauv septic AKI. Yog li, ALA tuaj yeem yog cov khoom lag luam zoo rau kev kho mob septic AKI.
3.3. Lub raum Ischemic Reperfusion
Ischemia tshwm sim thaum muaj qhov txo qis hauv cov ntshav perfusion thiab cov ntshav ntws mus rau hauv nruab nrog cev tau txo qis [74]; Qhov no yog vim muaj ntau yam ua rau, xws li thrombi, raug mob, thiab atherosclerosis [75]. Txhawm rau tiv thaiv cov ntaub so ntswg puas thiab necrosis, ischemia raug daws los ntawm reperfusion [75]. Txawm hais tias ischemic reperfusion yog qhov tseem ceeb los tiv thaiv cov ntaub so ntswg necrosis, nws tuaj yeem ua rau mob thiab nce cov pa oxygen reactive thiab reactive nitrogen hom [75-77]. Cov kev tshawb fawb tau pom tias kev kho ALA ua ntej tuaj yeem ua rau lub raum, retina, lub paj hlwb, daim siab, txoj hnyuv, thiab ntau dua [75]. Lub hauv paus kev tiv thaiv mechanisms ntawm ALA nyob rau hauv lub raum ischemia-reperfusion raug mob tej zaum yuav multifactorial, nrog rau counteracting oxidative puas [32,75] thiab downregulation ntawm channels, enzymes, thiab transporters, xws li aquaporins thiab sodium transporters, nrog rau sodium-potassium ATPase thiab Nitric Oxide Synthase isoforms [78] ALA kuj tseem tuaj yeem tiv thaiv lub raum ischemia-reperfusion raug mob los ntawm kev txo qis neutrophil infiltration thiab inhibiting kev tso tawm ntawm inflammatory mediators [79]. Cov kev tshawb fawb kuj tau pom tias lub raum cortical qauv kev puas tsuaj tshwm sim los ntawm limb ischemia-reperfusion raug mob tuaj yeem raug kho los ntawm ALA [80] thiab ALA, thiab thaum ua ke nrog xanthine oxidase inhibitor febuxostat, qhia tau hais tias muaj kev tiv thaiv zoo tshaj ntawm lub raum ischemia-reperfusion raug mob [81] . ALA kuj tseem tuaj yeem tiv thaiv lub raum tsis ua haujlwm thiab lub raum raug mob los ntawm kev txo qis ntawm endothelin ntau dhau -1 hauv lub raum ischemia-reperfusion raug mob [82].
3.4. Unilateral ureteral Obstruction (UUO)-Induced raum Injury
Lub unilateral ureteral obstruction (UUO) tsiaj qauv ntawm lub raum raug mob tau dav siv los soj ntsuam cov txheej txheem ntawm lub raum raug mob thiab kho qhov tseem ceeb ntawm ntau tus neeg sawv cev [83–87]. Cov qauv no muaj qee qhov zoo nyob rau hauv uas nws yog ib qho kev tsis sib haum xeeb uas tsis muaj qhov tsis zoo nyob rau hauv qhov tsis muaj qhov tshwm sim tshwm sim los yog kev ua phem rau lub raum [88]. Ntxiv mus, UUO qauv ntawm lub raum raug mob kuj yog ib qho qauv zoo rau kev kawm txog pathophysiology ntawm lub raum fibrosis [89-93]. Yog li ntawd, tus qauv UUO ntawm lub raum raug mob tuaj yeem ua tib zoo ua raws li cov hauv qab pathophysiology ntawm tib neeg obstructive raum raug mob [94,95]. ALA tau pom tias yog renoprotective tiv thaiv UUO-induced raum raug mob [88]. Wongmekiat et al. tau pom tias thaum ALA (60/mg/kg lub cev qhov hnyav) tau muab rau nas ntawm ip txhaj ob hnub ua ntej UUO induction thiab txuas ntxiv rau ib lub lim tiam tom qab UUO, UUO-vim lub raum tsis ua haujlwm, oxidative kev nyuaj siab, thiab tsim cov nitric oxide thiab hloov. qhov tseem ceeb-1 tau txo qis heev los ntawm kev kho ALA [88]. Tsis tas li ntawd, ALA kuj tau ua pov thawj los kho qhov kev hloov pauv ntawm epithelial-mesenchymal hauv tus qauv nas ntawm UUO raum raug mob [96]. Cov kev tshawb fawb no qhia tau hais tias ALA yog nephroprotective tiv thaiv UUO-induced raum raug mob.
3.5. Cisplatin-Induced Nephrotoxicity
Cisplatin yog cov tshuaj khomob uas kho mob qog noj ntshav los ntawm kev nkag mus rau hauv cov qog hlwb, tso cov tshuaj chloride ions, thiab ua kom cov dej nkag mus rau crosslink nrog DNA thiab tsim DNA adducts los tiv thaiv qog cell replication [97,98]. Txawm li cas los xij, cov tshuaj cisplatin muaj ntau yam kev mob tshwm sim, xws li ototoxicity, neurotoxicity, nephrotoxicity, xeev siab, thiab ntuav [35,97–99]. Nephrotoxicity tshwm sim vim hais tias cisplatin raug coj los ntawm cov tubular cov hlwb thiab tuaj yeem mloog zoo txog tsib zaug ntau dua li cisplatin hauv cov ntshav [35,97]. Cisplatin nephrotoxicity ua rau txo qis creatinine tshem tawm, nce cov ntshav creatinine, nce qib urea, nce zis tso zis, thiab txo glomerular pom tus nqi 100,1011. Cisplatin kuj txo cov antioxidants glutathione S-transferase, glutathione peroxidase thiab superoxide dismutase, ua rau nce hauv ROS thiab oxidative markers xws li MDA muab los ntawm lipid peroxidation [35,100,102]. Cov tubules nyob ze ntawm ob lub raum muaj ntau ntawm mitochondria (35]. Hydrolyzed cisplatin tsim cov metabolite nrog cov nqi zoo, thiab qhov no accumulates nyob rau hauv mitochondria vim mitochondria qhov tsis zoo nqi molecules, tsim kom muaj oxidative kev nyuaj siab (35) los tswj qhov no, mitochondria. siv endogenous antioxidants xws li lipoic acid los txo ROS (351. Cov kev tshawb fawb pom tau hais tias ALA tiv thaiv lub raum hlwb tiv thaiv cisplatin's toxicity (98], txo cov structural proximal tubular puas, thiab nce glomerular pom nyob rau hauv ob lub raum (99,103]. ALA kuj tau qhia rau Txo cov ntshav creatinine qib thiab tso zis tso zis, nce creatinine tshem tawm thiab tso zis osmolality, thiab normalize sodium excretion hauv cisplatin raum raug mob [101].
3.6. Folic Acid-Induced Nephrotoxicity
Cov qib siab ntawm folic acid tuaj yeem ua rau tubular puas tsuaj los ntawm kev tshem tawm thiab nthuav tawm ntawm cov tubular hlwb [104], ua rau cell tuag [105]. Ferroptosis yog hom cell tuag los ntawm hlau thiab lipid peroxidation uas tshwm sim thaum lub sij hawm folic acid-induced AKI [106]. Thaum muaj ntau cov hlau nyob hauv lub cev, ROS yog tsim, ua rau lipid peroxidation, ua rau cov lipid membranes, thiab ua rau cell tuag [105]. Nws tau raug tsim los hais tias ALA cov tshuaj tiv thaiv antioxidant tau ua rau muaj kev tiv thaiv kev tiv thaiv folic acid vim yog lub raum puas tsuaj [105]. Hauv kev tshawb fawb los ntawm Li et al., tsis muaj qhov sib txawv ntawm cov koob tshuaj tsawg thiab cov koob tshuaj ALA siab, qhia tias cov txiaj ntsig ntawm ALA tsis yog nyob ntawm koob tshuaj [105]. Tsis tas li ntawd, ALA tuaj yeem ua haujlwm los ntawm kev thaiv p53 los ntawm kev ua rau ferroptosis thiab los ntawm kev tswj hwm ferritin thiab ferroportin hlau xa tawm, yog li tiv thaiv folic acid-induced AKI [105]. Daim duab 6 qhia histologically pom qhov pom ntawm ALA tiv thaiv lub raum raug mob los ntawm folic acid [105].
3.7. Cadmium-Induced Nephrotoxicity
Cadmium yog cov hlau hnyav hnyav uas tshwm sim los ntawm nephrotoxicity [104,107–109]. Cadmium-induced nephrotoxicity nce MDA qib, ua rau muaj kev puas tsuaj rau lub raum mitochondria thiab lub raum cortex [110]. Cadmium kuj tau pom tias txo glutathione antioxidant (GSH), glutathione peroxidase, catalase, thiab superoxide dismutase (SOD) [110].
Kev kho mob nrog ALA ua haujlwm ua antioxidant kom txo tau MDA thiab apoptosis thiab chelate cadmium kom txo cadmium puas rau lub raum [111]. ALA kuj txo qis oxidative kev nyuaj siab, txhawb nqa glutathione-txog endogenous enzymes, thiab tiv thaiv mitochondrial apoptosis hauv cadmium-induced raum raug mob [110–112].
3.8. Iron-Induced Acute raum Injury
Hlau tau xav tias yuav pab txhawb rau AKI thiab CKD [113–118]. Tseeb tiag, nws tau raug pom tias lub raum tubules raug nce qib ntawm cov hlau hauv cov neeg mob raum kab mob, uas yog vim muaj kev pom ntau ntxiv ntawm cov hlau thiab cov protein uas muaj hlau los ntawm glomerular apparatus [114,117,119]. Hlau kuj tuaj yeem ua rau mob raum mob ntshav qab zib ntau ntxiv los ntawm kev ua kom oxidative kev nyuaj siab [120,121]. Yog li ntawd, cov qauv ntawm cov tsiaj raug tsim los ntawm lub raum raug mob yog ib qho cuab yeej tseem ceeb hauv kev kawm txog cov txheej txheem ntawm cov hlau ua rau lub raum raug mob thiab kuaj xyuas cov teebmeem ntawm cov khoom ntuj lossis cov tshuaj [122–125]. Hauv qhov no, ALA tau pom tias yog nephroprotective hauv ion-induced raum raug mob [126,127]. Nyob rau hauv ib tug hlau-overloading nas qauv ntawm lub raum raug mob, ALA tau pom los ua pov thawj antioxidant los ntawm attenuating oxidative puas [128]. ALA kuj tau pom tias inhibit p38 MAPK signaling thiab NADPH oxidase 4 qhia hauv cov hlau ua rau lub raum raug mob [127]. Nws yuav tsum tau muab sau tseg tias tag nrho cov kev tiv thaiv ntawm ALA nyob rau hauv cov hlau ua rau lub raum raug mob tej zaum yuav yog ib feem ntawm nws cov hlau-chelating cuab yeej [128–131], uas txo cov muaj hlau dawb.
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