Coenzyme Q10 attenuates lung and liver fibrosis via modulation of autophagy in methotrexate treated rat
Open accessAbstract
The present study was conducted to investigate the potential protective effects of coenzyme Q 10 (CoQ10) administration on methotrexate induced lung and liver fibrosis in rat model, and to explore our hypothesis regarding its possible mechanism of action through reactivation of autophagy pathway. Methotrexate induced fibrosis was achieved by intraperitoneal injections twice a week for 4 weeks. A combined treatment of CoQ10 and methotrexate were used. Blood samples for biochemical analysis, lung and livers tissue for biochemical and histopathological analysis, were investigated. Concomitant treatment of CoQ10 & methotrexate caused improvement in histological picture of the lung and liver tissues, liver function and oxidative stress biomarkers, modulation of autophagy genes [mammalian target of rapamycin (m-TOR), Microtubule-associated proteins 1 A/1B light chain 3 (MAP1LC3B), and Sequestosome 1 ubiquitin-binding protein p62 (p62/SQSTM1)] with simultaneous reduction in High Mobility Group Protein B1 (HMGB1). Based on our results we postulated that CoQ10 up regulates autophagy pathway that could explain its protective properties against lung and liver fibrosis caused by methotrexate treatment in current study rat model.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CoQ10 is a key cofactor in the electron transport chain, regulating oxidant/antioxidant balance and having a protective effect on mitochondria.
“This was endorsed by Mohamed et al. (2019) who stated that CoQ10 is the key cofactor in the electron transport chain via regulating the oxidant/antioxidant balance; thus, it has a protective effect on mitochondria.”
From Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle? (2023) · cites this paper as Mohamed et al. 2019
The Discussion calls CoQ10 a key cofactor in the electron transport chain, and the Results (section 4.2) show that it reversed oxidative-stress marker changes in methotrexate-treated rats. The paper does not establish the claimed protective effect on mitochondria or show that regulation of oxidant/antioxidant balance occurs through its electron-transport role. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Antioxidant activity of food constituents: an overview
Gülçın, İ. (2011) · Archives of Toxicology · doi:10.1007/s00204-011-0774-2 · Cited by 1,675 · see citing works
Endogenous HMGB1 regulates autophagy
Tang, D., Kang, R., Livesey, K. M., Cheh, C.-W., Farkas, A., Loughran, P., Hoppe, G., Bianchi, M. E., Tracey, K. J., Zeh, H. J., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911078 · Cited by 951 · see citing works
HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease
Harris, H. E., Andersson, U., & Pisetsky, D. S. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.222 · Cited by 689 · see citing works
Oxidative Stress and Autophagy
Kiffin, R., Bandyopadhyay, U., & Cuervo, A. M. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.152 · Cited by 527 · see citing works
Autophagy in Idiopathic Pulmonary Fibrosis
Patel, A. S., Lin, L., Geyer, A. I., Haspel, J. A., An, C. H., Cao, J., Rosas, I. O., & Morse, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041394 · Cited by 371 · see citing works
Mi, S., Li, Z., Yang, H.-Z., Liu, H., Wang, J.-P., Ma, Y.-G., Wang, X.-X., Liu, H.-Z., Sun, W., & Hu, Z.-W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004081 · Cited by 370 · see citing works
Insufficient autophagy in idiopathic pulmonary fibrosis
Araya, J., Kojima, J., Takasaka, N., Ito, S., Fujii, S., Hara, H., Yanagisawa, H., Kobayashi, K., Tsurushige, C., Kawaishi, M., et al. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00213.2012 · Cited by 326 · see citing works
Proliferative and Nonproliferative Lesions of the Rat and Mouse Respiratory Tract
Renne, R. A., Brix, A. E., Harkema, J. R., Herbert, R. A., Kittel, B., Lewis, D., March, T. H., Nagano, K., Pino, M. V., Rittinghausen, S., et al. (2009) · Toxicologic Pathology · doi:10.1177/0192623309353423 · Cited by 324 · see citing works
Romero, Y., Bueno, M., Ramı́rez, R., Álvarez, D., Sembrat, J., Goncharova, E. A., Rojas, M. M., Selman, M., Mora, A. L., & Pardo, A. (2016) · Aging Cell · doi:10.1111/acel.12514 · Cited by 190 · see citing works
The Role of High Mobility Group Box1 in Pulmonary Fibrosis
Hamada, N., Maeyama, T., Kawaguchi, T., Yoshimi, M., Fukumoto, J., Yamada, M., Yamada, S., Kuwano, K., & Nakanishi, Y. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0330oc · Cited by 188 · see citing works
Jang, S. I., Kim, H. J., Kim, Y., Jeong, S.-I., & You, Y. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.04.044 · Cited by 181 · see citing works
Şener, G., Ekşioğlu, E., Çetiner, M., Ercan, F., & Yeğen, B. Ç. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.02.056 · Cited by 157 · see citing works
Mahmoud, A. M., Hussein, O. E., Hozayen, W. G., & El-Twab, S. M. A. (2017) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2017.04.009 · Cited by 154 · see citing works
In vivo antioxidant treatment protects against bleomycin‐induced lung damage in rats
Serrano‐Mollar, A., Closa, D., Prats, N., Blesa, S., Martínez‐Losa, M., Cortijo, J., Estrela, J. M., Morcillo, E. J., & Bulbena, O. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705138 · Cited by 123 · see citing works
Farsi, F., Mohammadshahi, M., Alavinejad, P., Rezazadeh, A., Zarei, M., & Engali, K. A. (2015) · Journal of the American College of Nutrition · doi:10.1080/07315724.2015.1021057 · Cited by 116 · see citing works
Protective Effect of β-Carotene on Methotrexate–Induced Oxidative Liver Damage
Vardı, N., Parlakpınar, H., Çetin, A., et al. (2010) · Toxicologic Pathology · doi:10.1177/0192623310367806 · Cited by 112 · see citing works
Resveratrol Protects Against Methotrexate-Induced Hepatic Injury in Rats
Akbay, T. T., Şehırlı, Ö., Ercan, F., et al. (2010) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j30k5q · Cited by 105 · see citing works
Oxidative stress and mRNA expression of acetylcholinesterase in the leukocytes of ischemic patients
Işık, M., Beydemir, Ş., Yılmaz, A., Naldan, M. E., Duran, H. E., & Gülçın, İ. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.01.003 · Cited by 98 · see citing works
mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis
Gui, Y.-S., Wang, L., Tian, X., Li, X., Ma, A., Zhou, W., Zeng, N., Zhang, J., Cai, B., Zhang, H., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138625 · Cited by 94 · see citing works
Akbulut, S. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i29.10158 · Cited by 93 · see citing works
Emerging role of HMGB 1 in fibrotic diseases
Li, L., Gao, J., & Li, J. (2014) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12419 · Cited by 93 · see citing works
Tarry‐Adkins, J. L., Fernandez‐Twinn, D. S., Hargreaves, I. P., Neergheen, V., Aiken, C., Martin‐Gronert, M. S., McConnell, J. M. L., & Ozanne, S. E. (2015) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.115.119834 · Cited by 89 · see citing works
Mirmalek, S. A., Boushehrinejad, A. G., Yavari, H., et al. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/5818479 · Cited by 80 · see citing works
Ulla, A., Mohamed, M. K., Sikder, B., Rahman, A. T., Sumi, F. A., Hossain, M., Reza, H. M., Rahman, G. M. S., & Alam, M. A. (2017) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-017-0136-7 · Cited by 80 · see citing works
Xu, K., Cai, Y., Lu, S., Li, X.-L., Liu, L., Zhong, L., Liu, H., & Xu, P. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0892-y · Cited by 79 · see citing works
Shao, L., Ping, Z., & Jin, G. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/9863181 · Cited by 76 · see citing works
Çalıkoğlu, M. E. (2003) · Pharmacological Research · doi:10.1016/s1043-6618(03)00156-7 · Cited by 74 · see citing works
Autophagy: A new player in hepatic stellate cell activation
Thoen, L. F. R., Guimarães, E. L. M., & van Grunsven, L. A. (2012) · Autophagy · doi:10.4161/auto.8.1.18105 · Cited by 71 · see citing works
Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro
Ohbayashi, M., Suzuki, M., Yashiro, Y., et al. (2010) · The Journal of Toxicological Sciences · doi:10.2131/jts.35.653 · Cited by 70 · see citing works
Mustafa, H. N., Awdan, S. A. E., Hegazy, G. A., et al. (2015) · Indian Journal of Pharmacology · doi:10.4103/0253-7613.169588 · Cited by 67 · see citing works
Involvement of epithelial-mesenchymal transition in methotrexate-induced pulmonary fibrosis
Ohbayashi, M., Kubota, S., Kawase, A., Kohyama, N., Kobayashi, Y., & Yamamoto, T. (2014) · The Journal of Toxicological Sciences · doi:10.2131/jts.39.319 · Cited by 62 · see citing works
Exopolysaccharide and lactic acid bacteria: Perception, functionality and prospects
Bajpai, V. K., Rather, I. A., Majumder, R., Shukla, S., Aeron, A., Kim, K., Kang, S. C., Dubey, R. C., Maheshwari, D. K., Lim, J., et al. (2015) · Bangladesh Journal of Pharmacology · doi:10.3329/bjp.v11i1.23819 · Cited by 61 · see citing works
Autophagy: A new therapeutic target for liver fibrosis
Mao, Y. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i16.1982 · Cited by 53 · see citing works
Coenzyme Q10 supplementation reduces corticosteroids dosage in patients with bronchial asthma
Gvozdjáková, A., Kucharská, J., Bartkovjaková, M., et al. (2005) · BioFactors · doi:10.1002/biof.5520250129 · Cited by 50 · see citing works
Tsai, C.-W., Lai, F.-J., Sheu, H.-M., Lin, Y.-S., Chang, T.-H., Jan, M.-S., Chen, S. M., Hsu, P.-C., Huang, T.-T., Huang, T.-C., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.308 · Cited by 48 · see citing works
The effects of lycopene on methotrexate-induced liver injury in rats
Yücel, Y., Oğuz, E., Koçarslan, S., et al. (2017) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2017_042 · Cited by 45 · see citing works
Variation of immunological response in methotrexate-induced pneumonitis
Chikura, B., Sathi, N., Lane, S., et al. (2008) · Lara D. Veeken · doi:10.1093/rheumatology/ken356 · Cited by 40 · see citing works
Fikry, E. M., Safar, M. M., Hasan, W. A., et al. (2015) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.21701 · Cited by 38 · see citing works
Tawfik, M. K. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.11.018 · Cited by 38 · see citing works
Methotrexate-induced Hepatic and Renal Toxicity: Role of L-carnitine in Treatment
Tousson, E., Zaki, Z. T., Abu-Shaeir, W. A., & Hassan, H. M. (2014) · Biomedicine and Biotechnology · doi:10.12691/bb-2-4-4 · Cited by 34 · see citing works
The Effect of Co-Enzyme Q10 on Acute Liver Damage in Rats, a Biochemical and Pathological Study
Ashkani‐Esfahani, S., Esmaeilzadeh, E., Bagheri, F., Emami, Y., & Farjam, M. (2013) · Hepatitis Monthly · doi:10.5812/hepatmon.13685 · Cited by 32 · see citing works
mTOR Overactivation in Mesenchymal cells Aggravates CCl4− Induced liver Fibrosis
Shan, L., Ding, Y., Fu, Y., Zhou, L., Dong, X., Chen, S., Wu, H., Nai, W., Zheng, H., Xu, W., et al. (2016) · Scientific Reports · doi:10.1038/srep36037 · Cited by 31 · see citing works
Efectos protectores de infliximab sobre el daño pulmonar inducido por metotrexato
Kurt, A., Tümkaya, L., Türüt, H., et al. (2015) · Archivos de Bronconeumología · doi:10.1016/j.arbres.2015.03.018 · Cited by 30 · see citing works
Protective Effects of Infliximab on Lung Injury Induced by Methotrexate
Kurt, A., Tümkaya, L., Türüt, H., et al. (2015) · Archivos de Bronconeumología · doi:10.1016/j.arbr.2015.05.012 · Cited by 30 · see citing works
Protective effect of Naringin on experimental hindlimb ischemia/reperfusion injury in rats
Gürsul, C., Akdemi̇r, F. N. E., Akkoyun, T., et al. (2016) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.3109/14756366.2016.1167050 · Cited by 27 · see citing works
Botham, K. M., Napolitano, M., & Bravo, E. (2015) · Nutrients · doi:10.3390/nu7125501 · Cited by 19 · see citing works
Liu, M., He, Y., & Zhang, J. (2013) · PubMed · Cited by 14 · see citing works
Effects of Coenzyme Q10 on Rat Liver Cells under Conditions of Metabolic Stress
Vasiliev, A. V., Martinova, E. A., Sharanova, N. V., & Gapparov, M. M. G. (2011) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-011-1156-8 · Cited by 13 · see citing works
Jafarvand, E., Farhangi, M. A., Alipour, B., & Khoshbaten, M. (2015) · Bangladesh Journal of Pharmacology · doi:10.3329/bjp.v11i1.24513 · Cited by 11 · see citing works
The antioxidant effect of boric acid and CoQ10 on pulmonary fibrosis in bleomycin induced rats
Çelikezen, F. Ç., Oto, G., Özdemir, H., Kömüroğlu, U., Yoruk, I. H., Demir, H., & Yeltekin, A. Ç. (2015) · Bitlis Eren University Journal of Science and Technology · doi:10.17678/beuscitech.47149 · Cited by 8 · see citing works
Protective role of Coenzyme Q10 in two models of rat lung injury
Lim, H., Jayaweera, S., Calderone, A., et al. (2009) · ANZ Journal of Surgery · doi:10.1111/j.1445-2197.2009.05085.x · Cited by 7 · see citing works
Emam, A. M., Georgy, G. S., Shaker, O. G., et al. (2016) · Der pharmacia lettre · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Can coenzyme Q10 alleviate the toxic effect of fenofibrate on skeletal muscle?
El-Bassouny, D. R., Mansour, A. A., Ellakkany, A. S., Ayuob, N. N., & AbdElfattah, A. A. (2023) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02205-5
- Authors
- Mohamed, D. I., Khairy, E., Tawfek, S. S., Habib, E. K., & Fetouh, M. A.
- Affiliations
- Ain Shams University (EG)
- Corresponding author
- Mohamed, Doaa I.
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 109
- Pages
- 892-901
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2900428717
- Cited by
- 62
- References
- 52
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 11 · 2023: 12 · 2022: 8 · 2021: 6 · 2020: 10 · 2019: 5
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Pathology and Forensic Medicine › Chemotherapy-induced organ toxicity mitigation
- Keywords
- coenzyme Q10, pulmonary fibrosis, liver fibrosis, autophagy, oxidative stress, HMGB1, mTOR, LC3B, p62, hepatotoxicity, nephrotoxicity
- MeSH terms
- Animals, Antioxidants, Autophagy, Enzyme Inhibitors, Liver Cirrhosis, Lung, Male, Methotrexate, Ubiquinone, Rats, Wistar, Oxidative Stress, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
