Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats

Simple item page
dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorFayez A.M.
dc.contributor.authorZakaria S.
dc.contributor.authorMoustafa D.
dc.contributor.otherDepartment of Pharmacology and Toxicology
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherMSA University
dc.contributor.otherOctober City 6
dc.contributor.otherGiza
dc.contributor.otherEgypt; Department of Pharmacology and Toxicology
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober 6 University
dc.contributor.otherOctober City 6
dc.contributor.otherGiza
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:40:52Z
dc.date.available2020-01-09T20:40:52Z
dc.date.issued2018
dc.descriptionScopus
dc.descriptionMSA Google Scholar
dc.description.abstractHepatic injury is a major side effect associated with methotrexate (MTX) therapy resulting from inflammatory reactions and oxidative stress induction. Therefore, liver fibrosis incidence is augmented with long-term MTX therapy. Alpha lipoic acid (ALA) is a naturally occurring compound with potent antioxidant activity. This study explored the hepatoprotective mechanisms of ALA against MTX-induced hepatic injury in rats. Hepatic injury was induced in MTX group by 20 mg/kg body weight ip. injection of MTX. ALA group was pretreated with ALA 60 mmol/kg body weight ip. for five days followed by a single dose of MTX in the sixth day. Blood samples and liver tissues were then obtained to assess several biochemical parameters as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), reduced glutathione (GSH), total antioxidant capacity (TAC) and lipid peroxidation. Nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway was studied by determining the extent of mRNA Nrf2 expression and the level of HO-1. Hepatic stellate cells (HSCs) activation was evaluated by estimating the expression of ?-smooth muscle actin (?-SMA) and hydroxyproline content. Also, tumor necrosis factor alpha (TNF-?), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and caspase-3 were assessed by ELISA in addition to histopathological examination of liver samples. Results showed that ALA pretreatment improved liver function since serum ALT, AST and ALP levels were reduced. Additionally, ALA restored GSH and TAC levels when compared to MTX group and decreased lipid peroxidation. ALA exerted its antioxidant effect via Nrf2/HO-1 pathway as well as it showed anti-inflammatory and antiapoptotic effects by reducing TNF-? iNOS, COX-2 and caspase-3 levels in liver tissue homogenate. Finally, ALA suppressed HSCs activation by decreasing ?-SMA expression and hydroxyproline content in liver. It was concluded that ALA has hepatoprotective effects against MTX-induced hepatic injury mediated by Nrf2/HO-1 pathway as well as anti-inflammatory and antiapoptotic properties. � 2018 Elsevier Masson SASen_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=28620&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1016/j.biopha.2018.05.145
dc.identifier.doiPubMed ID 29879626
dc.identifier.issn7533322
dc.identifier.otherhttps://doi.org/10.1016/j.biopha.2018.05.145
dc.identifier.otherPubMed ID 29879626
dc.identifier.urihttps://t.ly/kNq39
dc.language.isoEnglishen_US
dc.publisherElsevier Masson SASen_US
dc.relation.ispartofseriesBiomedicine and Pharmacotherapy
dc.relation.ispartofseries105
dc.subjectOctober University for Modern Sciences and Arts
dc.subjectجامعة أكتوبر للعلوم الحديثة والآداب
dc.subjectUniversity of Modern Sciences and Arts
dc.subjectMSA University
dc.subjectAntimicrobial sensitivity
dc.subjectGastric
dc.subjectcancer H.
dc.subjectpylori
dc.subjectAlpha lipoic aciden_US
dc.subjectHepatic stellate cellsen_US
dc.subjectInflammatory responsesen_US
dc.subjectMethotrexateen_US
dc.subjectNrf2/HO-1 pathwayen_US
dc.subjectOxidative stressen_US
dc.subject?-Smooth muscle actinen_US
dc.subjectalkaline phosphataseen_US
dc.subjectalpha smooth muscle actinen_US
dc.subjectaspartate aminotransferaseen_US
dc.subjectcaspase 3en_US
dc.subjectcyclooxygenase 2en_US
dc.subjectglutathioneen_US
dc.subjectheme oxygenase 1en_US
dc.subjecthydroxyprolineen_US
dc.subjectinducible nitric oxide synthaseen_US
dc.subjectmessenger RNAen_US
dc.subjectmethotrexateen_US
dc.subjectthioctic aciden_US
dc.subjecttranscription factor Nrf2en_US
dc.subjecttumor necrosis factoren_US
dc.subjectantioxidanten_US
dc.subjectbiological markeren_US
dc.subjectheme oxygenase 1en_US
dc.subjectmethotrexateen_US
dc.subjectthioctic aciden_US
dc.subjecttranscription factor Nrf2en_US
dc.subjectalanine aminotransferase blood levelen_US
dc.subjectalkaline phosphatase blood levelen_US
dc.subjectanimal experimenten_US
dc.subjectanimal modelen_US
dc.subjectanimal tissueen_US
dc.subjectantiinflammatory activityen_US
dc.subjectantioxidant activityen_US
dc.subjectArticleen_US
dc.subjectaspartate aminotransferase blood levelen_US
dc.subjectcell activationen_US
dc.subjectcontrolled studyen_US
dc.subjectdrug mechanismen_US
dc.subjectenzyme linked immunosorbent assayen_US
dc.subjecthepatic stellate cellen_US
dc.subjecthistopathologyen_US
dc.subjectlipid peroxidationen_US
dc.subjectliver functionen_US
dc.subjectliver injuryen_US
dc.subjectliver protectionen_US
dc.subjectliver tissueen_US
dc.subjectmaleen_US
dc.subjectmRNA expression levelen_US
dc.subjectnonhumanen_US
dc.subjectpriority journalen_US
dc.subjectprotein expression levelen_US
dc.subjectraten_US
dc.subjecttissue homogenateen_US
dc.subjectanimalen_US
dc.subjectapoptosisen_US
dc.subjectchemistryen_US
dc.subjectdrug effecten_US
dc.subjecthepatic stellate cellen_US
dc.subjectinflammationen_US
dc.subjectliveren_US
dc.subjectmetabolismen_US
dc.subjectoxidative stressen_US
dc.subjectpathologyen_US
dc.subjectpathophysiologyen_US
dc.subjectsignal transductionen_US
dc.subjectAnimalsen_US
dc.subjectAntioxidantsen_US
dc.subjectApoptosisen_US
dc.subjectBiomarkersen_US
dc.subjectHeme Oxygenase-1en_US
dc.subjectHepatic Stellate Cellsen_US
dc.subjectInflammationen_US
dc.subjectLiveren_US
dc.subjectMaleen_US
dc.subjectMethotrexateen_US
dc.subjectNF-E2-Related Factor 2en_US
dc.subjectOxidative Stressen_US
dc.subjectRatsen_US
dc.subjectSignal Transductionen_US
dc.subjectThioctic Aciden_US
dc.titleAlpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in ratsen_US
dc.typeArticleen_US
dcterms.isReferencedByMoghadam, A.R., Tutunchi, S., Namvaran-Abbas-Abad, A., Yazdi, M., Bonyadi, F., Mohajeri, D., Mazani, M., Ghavami, S., Pre-administration of turmeric prevents methotrexate-induced liver toxicity and oxidative stress (2015) BMC Complement. Altern. Med., 15 (246); Jaeschke, H., Woolbright, B.L., Current strategies to minimize hepatic ischemia�reperfusion injury by targeting reactive oxygen species (2012) Transpl. Rev., 26, pp. 103-114; Prestigiacomo, V., Weston, A., Messner, S., Lampart, F., Suter-Dick, L., Pro-fibrotic compounds induce stellate cell activation, ECM-remodelling and Nrf2 activation in a human 3D-multicellular model of liver fibrosis (2017) PLoS One, 12; Famurewa, A.C., Ufebe, O.G., Egedigwe, C.A., Nwankwo, O.E., Obaje, G.S., Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats (2017) Biomed. Pharmacother., 87, pp. 437-442; Rockey, D.C., Weymouth, N., Shi, Z., Paquet, N., Ravier, F., Smooth muscle ? actin (Acta2) and myofibroblast function during hepatic wound healing (2013) PLoS One, 8; Yu, J., Wu, C.W., Chu, E.S.H., Hui, A.Y., Cheng, A.S.L., Go, M.Y.Y., Ching, A.K.K., Sung, J.J.Y., Elucidation of the role of COX-2 in liver fibrogenesis using transgenic mice (2008) Biochem. Biophys. Res. Commun., 372, pp. 571-577; Anavi, S., Eisenberg-Bord, M., Hahn-Obercyger, M., Genin, O., Pines, M., Tirosh, O., The role of iNOS in cholesterol-induced liver fibrosis (2015) Lab. Investig., 95, pp. 914-924; Jeon, M.J., Kim, W.G., Lim, S., Choi, H.-J., Sim, S., Kim, T.Y., Shong, Y.K., Kim, W.B., Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells (2016) Mol. Cell. Endocrinol., 419, pp. 113-123; Shi, C., Zhou, X., Zhang, J., Wang, J., Xie, H., Wu, Z., ?-Lipoic acid protects against the cytotoxicity and oxidative stress induced by cadmium in HepG2 cells through regeneration of glutathione by glutathione reductase via Nrf2/ARE signaling pathway (2016) Environ. Toxicol. Pharmacol., 45, pp. 274-281; Hu, H., Wang, C., Jin, Y., Meng, Q., Liu, Q., Liu, K., Sun, H., Alpha-lipoic acid defends homocysteine-induced endoplasmic reticulum and oxidative stress in HAECs (2016) Biomed. Pharmacother., 80, pp. 63-72; Ma, Q., Li, Y., Fan, Y., Zhao, L., Wei, H., Ji, C., Zhang, J., Molecular mechanisms of lipoic acid protection against aflatoxin B?-induced liver oxidative damage and inflammatory responses in broilers (2015) Toxins (Basel), 7, pp. 5435-5447; Piechota-Polanczyk, A., Zieli?ska, M., Piekielny, D., Fichna, J., The influence of lipoic acid on caveolin-1-regulated antioxidative enzymes in the mouse model of acute ulcerative colitis (2016) Biomed. Pharmacother., 84, pp. 470-475; Li, J., Hu, R., Xu, S., Li, Y., Qin, Y., Wu, Q., Xiao, Z., Xiaochaihutang attenuates liver fibrosis by activation of Nrf2 pathway in rats (2017) Biomed. Pharmacother., 96, pp. 847-853; Ge, M., Yao, W., Yuan, D., Zhou, S., Chen, X., Zhang, Y., Li, H., Hei, Z., Brg1-mediated Nrf2/HO-1 pathway activation alleviates hepatic ischemia-reperfusion injury (2017) Cell Death Dis., 8, p. e2841; �ak?r, T., Ba?t�rk, A., Polat, C., Aslaner, A., Durgut, H., ?ehirli, A.�., G�l, M., Oru�, M.T., Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? (2015) Acta Cir�rgica Bras. / Soc. Bras. Para Desenvolv. Pesqui. Em Cir., 30, pp. 247-252; Bancroft, J.D.C., (Histologist) Layton, S.K. Suvarna, Bancroft's theory and practice of histological techniques, n.d; Ohkawa, H., Ohishi, N., Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction (1979) Anal. Biochem., 95, pp. 351-358; Jollow, D., Mitchell, J.R., Zampaglione, N., Gillette, J.R., Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite (1974) Pharmacology, 11, pp. 151-169; Stamp, L., Roberts, R., Kennedy, M., Barclay, M., O'Donnell, J., Chapman, P., The use of low dose methotrexate in rheumatoid arthritis - are we entering a new era of therapeutic drug monitoring and pharmacogenomics? (2006) Biomed. Pharmacother., 60, pp. 678-687; Al Maruf, A., O'Brien, P.J., Naserzadeh, P., Fathian, R., Salimi, A., Pourahmad, J., Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes (2017) Drug. Chem. Toxicol., pp. 1-11; Mahmoud, A.M., Hussein, O.E., Hozayen, W.G., Abd El-Twab, S.M., Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPAR? and Nrf2: protective effect of 18?-glycyrrhetinic acid (2017) Chem. Biol. Interact., 270, pp. 59-72; Khalifa, M.M.A., Bakr, A.G., Osman, A.T., Protective effects of phloridzin against methotrexate-induced liver toxicity in rats (2017) Biomed. Pharmacother., 95, pp. 529-535; Montasser, A.O.S., Saleh, H., Ahmed-Farid, O.A., Saad, A., Marie, M.-A.S., Protective effects of Balanites aegyptiaca extract, Melatonin and Ursodeoxycholic acid against hepatotoxicity induced by Methotrexate in male rats (2017) Asian Pac. J. Trop. Med., 10, pp. 557-565; I, E.E., Ii, Y.I., Naile, P., Iii, G., Iv, Y.O., V, T.T., Vi, E.O., Rutin ameliorates methotrexate induced hepatic injury in rats 1, 30 (n.d.) 778�784. doi:; Sotoudehmanesh, R., Anvari, B., Akhlaghi, M., Shahraeeni, S., Kolahdoozan, S., Sotoudehmanesh, R., Methotrexate hepatotoxicity in patients with rheumatoid arthritis (2010) Middle East J. Dig. Dis., 2; Kose, E., Sapmaz, H.I., Sarihan, E., Vardi, N., Turkoz, Y., Ekinci, N., Beneficial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study (2012) Sci. World J., 2012; Abdel-Daim, M.M., Khalifa, H.A., Abushouk, A.I., Dkhil, M.A., Al-Quraishy, S.A., Diosmin attenuates methotrexate-induced hepatic, renal, and cardiac injury: a biochemical and histopathological study in mice (2017) Oxid. Med. Cell. Longev., 2017; Ghelani, H., Razmovski-Naumovski, V., Nammi, S., Chronic treatment of (R)- ? -lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats (2017) Pharmacol. Res. Perspect., 5, p. e00306; El-Sayed, E.-S.M., Mansour, A.M., El-Sawy, W.S., Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats (2017) J. Biochem. Mol. Toxicol., 31, p. e21940; Zamani, E., Shaki, F., AbedianKenari, S., Shokrzadeh, M., Acrylamide induces immunotoxicity through reactive oxygen species production and caspase-dependent apoptosis in mice splenocytes via the mitochondria-dependent signaling pathways (2017) Biomed. Pharmacother., 94, pp. 523-530; Niki, E., Lipid peroxidation products as oxidative stress biomarkers (2008) Biofactors, 34, pp. 171-180. , http://www.ncbi.nlm.nih.gov/pubmed/19706982, (Accessed 9 September, 2017); A.V, V., K, R.R., Kurrey, N.K., K.A, A.A., G, V., Protective effects of phenolics rich extract of ginger against Aflatoxin B 1 -induced oxidative stress and hepatotoxicity (2017) Biomed. Pharmacother., 91, pp. 415-424; Savran, M., Cicek, E., Doguc, D., Asci, H., Yesilot, S., Candan, I., Dagdeviren, B., Ozer, M., Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats (2017) Physiol. Int., 104, pp. 139-149; Ateyya, H., Nader, M.A., Attia, G.M., El-Sherbeeny, N.A., Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats (2017) Can. J. Physiol. Pharmacol., 95, pp. 492-500; Khalaf, A., Zaki, A., Galal, M., Ogaly, H., Ibrahim, M., Hassan, A., The potential protective effect of ?-lipoic acid against nanocopper particle�induced hepatotoxicity in male rats (2017) Hum. Exp. Toxicol., 36, pp. 881-891; Savran, M., Cicek, E., Doguc, D., Asci, H., Yesilot, S., Candan, I., Dagdeviren, B., Ozer, M., Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats (2017) Physiol. Int., 104, pp. 139-149; Martin, D., Rojo, A.I., Salinas, M., Diaz, R., Gallardo, G., Alam, J., de Galarreta, C.M.R., Cuadrado, A., Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol (2004) J. Biol. Chem., 279, pp. 8919-8929; Mahmoud, A.M., Hozayen, W.G., Ramadan, S.M., Berberine ameliorates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPAR? and suppressing oxidative stress and apoptosis in rats (2017) Biomed. Pharmacother., 94, pp. 280-291; Mahmoud, A.M., Hussein, O.E., Hozayen, W.G., Abd El-Twab, S.M., Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPAR? and Nrf2: protective effect of 18?-glycyrrhetinic acid (2017) Chem. Biol. Interact., 270, pp. 59-72; Ali, N., Rashid, S., Nafees, S., Hasan, S.K., Shahid, A., Majed, F., Sultana, S., Protective effect of chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: an experimental approach (2017) Chem. Biol. Interact., 272, pp. 80-91; Abo-Haded, H.M., Elkablawy, M.A., Al-johani, Z., Al-ahmadi, O., El-Agamy, D.S., Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity (2017) PLoS One, 12; Sokar, S.S., El-Sayad, M.E.-S., Ghoneim, M.E.-S., Shebl, A.M., Combination of sitagliptin and silymarin ameliorates liver fibrosis induced by carbon tetrachloride in rats (2017) Biomed. Pharmacother., 89, pp. 98-107; Tsuchida, T., Friedman, S.L., Mechanisms of hepatic stellate cell activation (2017) Nat. Rev. Gastroenterol. Hepatol., 14, pp. 397-411
dcterms.sourceScopus

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
avatar_scholar_256.png
Size:
6.31 KB
Format:
Portable Network Graphics
Description:
Download

Collections

Faculty Of Pharmacy Research Paper