α-Lipoic acid modulates liver fibrosis: A cross talk between TGF-β1, autophagy, and apoptosis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Maadawy W.H.; Hammam O.A.; Seif el-Din S.H.; El-Lakkany N.M.

Journal: Human and Experimental Toxicology

Publisher: SAGE Publications Ltd

Publication Date: 4 December 2019

Volume / Issue: Volume 39 / Issue 4

Pages: 440–450

ISSN: 9603271

DOI: 10.1177/0960327119891212

Scopus: View on Scopus

PubMed: 31797693

Document Type: Article

Authors and Affiliations

El-Maadawy W.H., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt; Hammam O.A., Department of Pathology, Theodor Bilharz Research Institute, Giza, Egypt; Seif el-Din S.H., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt; El-Lakkany N.M., Department of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Autophagy and apoptosis are important players in the progression of hepatic fibrosis via activation of hepatic stellate cells (HSCs). Despite the recently depicted antifibrotic effects of alpha-lipoic acid (ALA), however, its modulatory effects on HSCs autophagy remain unverified. Our study aimed to elucidate the underlying antifibrotic mechanisms through which ALA mediates HSC autophagy and apoptosis. Liver fibrosis was induced via thioacetamide (TAA) intoxication in rats; TAA-intoxicated rats were treated with either silymarin or ALA. Effect of ALA on biochemical parameters and immunohistopathological examinations was measured and compared to silymarin. ALA restored normal hepatic architecture (S1 vs. S4), liver functions, hepatic glutathione, and transforming growth factor-β1 levels. ALA ameliorated hepatic levels of malondialdehyde, platelet-derived growth factor, tissue inhibitor metalloproteinases-1, hydroxyproline, and expression of alpha-smooth muscle actin. Moreover, ALA significantly reduced messenger RNA expression of LC3-II genes and triggered caspase-3 expression. Interestingly, ALA exhibited superior activities over silymarin regarding suppression of proliferation, activation and autophagy of HSCs, collagen deposition, and induction of HSCs apoptosis. In conclusion, treatment of TAA-intoxicated rats with ALA inhibited autophagy and induced apoptotic clearance of activated HSCs. Accordingly, this study provides mechanistic insights into the possible applicability of ALA in the treatment of hepatic fibrosis. © The Author(s) 2019.

Keywords

Alpha-lipoic acid; apoptosis; autophagy; hepatic fibrosis; hepatic stellate cells; transforming growth factor-β1; Animals; Biomarkers; Disease Models, Animal; Liver Cirrhosis; Male; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Silymarin; Thioacetamide; Thioctic Acid; Transforming Growth Factor beta1; alpha smooth muscle actin; caspase 3; collagen; glutathione; hydroxyproline; malonaldehyde; messenger RNA; platelet derived growth factor; thiotacid; tissue inhibitor of metalloproteinase 1; biological marker; protective agent; animal experiment; animal model; animal tissue; Article; autophagy (cellular); biochemistry; cell activation; cell proliferation; controlled study; gene expression; immunopathology; liver fibrosis; liver function; molecular interaction; mouse; nonhuman; priority journal; protein expression; animal; disease model; drug effect; metabolism; pathology; rat; Sprague Dawley rat

Citation Information

Scopus Citations: 21

For comprehensive information about the Theodor Bilharz Research Institute (TBRI), its institutional activities, scientific and research achievements, clinical and hospital services, and the diverse expertise offered through its 22 specialized research and clinical departments, as well as opportunities for professional training, specialized workshops, and scientific conferences, readers are invited to visit the Institute’s official website.

The website provides regularly updated information on the Institute’s latest news, research activities, scientific initiatives, clinical services, institutional programs, and academic and professional opportunities.

English Website: https://www.tbri.sci.eg/en/

Arabic Website: https://www.tbri.sci.eg/ar/

Prepared and Uploaded by:

Abdalla F. Abdalla

Electronic Portal Unit

Electronic Portal Unit

Popular Posts

A cost-performance index for nano-optical biosensor evaluation: Systematic evaluation of europium–salicylate luminescent platforms for GPC3-targeted early HCC diagnosis

Image
Bibliographic Information Authors: Hassan Y.M.; El-Tantawi H.; Ali I.R.; Attia M.S. Journal: Talanta Publisher: Elsevier B.V. Publication Date: January 2027 Volume / Issue: Volume 311 Article No.: 130103 ISSN: 399140 DOI: 10.1016/j.talanta.2026.130103 Scopus: View on Scopus PubMed: 42391698 Document Type: Review Authors and Affiliations Hassan Y.M., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; El-Tantawi H., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Ali I.R., Department of Immunology and Treatment Evaluation, Theodore Bilharz Research Institute, Giza, Egypt; Attia M.S., Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia Abstract Comparative evaluation of nano-optical biosensor platforms lacks a standardised, multi-parameter quantitative framework that integrates analytical performance...
Read more

Interpretation of liver stiffness measurement in patients with mixed liver disease etiologies

Image
Bibliographic Information Authors: El Ray A.; El Ghannam M.; Rautou P.E. Journal: Arab Journal of Gastroenterology Publisher: Elsevier Ltd Publication Date: August 2026 ISSN: 16871979 DOI: 10.1016/j.ajg.2026.05.002 Scopus: View on Scopus PubMed: 42362465 Document Type: Letter Authors and Affiliations El Ray A., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt, Faculty of Medicine, October 6 University, Egypt; El Ghannam M., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt; Rautou P.E., Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France, AP-HP, Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France Abstract Vibration-controlled transient elastography (VCTE)–based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and p...
Read more

Variable clinical presentations of pulmonary hydatid cysts: a four-case series from a single center in United Arab Emirates, non-endemic region

Image
Bibliographic Information Authors: Yehya M.; Abdallah M.F.H.; Ajeka S.; Al-Masalmeh F.H.; Albaghdadi M.O.J. Journal: Journal of Surgical Case Reports Publisher: Oxford University Press Publication Date: 29 July 2026 Volume / Issue: Volume 2026 / Issue 7 Article No.: rjag658 ISSN: 20428812 DOI: 10.1093/jscr/rjag658 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Yehya M., Department of Thoracic Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Abdallah M.F.H., Department of Radiology, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates, Theodor Bilharz Research Institute, Mahad Al Abhas Al bahari St, Kornish Al Nile, Warraq Al Arab, Al Warak, Governorate, Giza, 3863341, Egypt; Ajeka S., Department of General Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Al-Masalmeh F.H., Department of ...
Read more

Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Image
Bibliographic Information Authors: Mansour E.M.; Shemis M.; Fahmy S.R.; Amer M.A.; Mohamed A.S. Journal: Current Nanomedicine Publisher: Bentham Science Publishers Publication Date: September 2026 Volume / Issue: Volume 16 / Issue 5 Pages: 771–786 ISSN: 24681873 DOI: 10.2174/0124681873401484250924125945 Scopus: View on Scopus Document Type: Article Authors and Affiliations Mansour E.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Shemis M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy S.R., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Amer M.A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Mohamed A.S., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt Abstract Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various conseq...
Read more

Mytilus edulis-mediated green synthesis of selenium nanoparticles with antimicrobial and molluscicidal applications

Image
Bibliographic Information Authors: Dokmak H.-A.A.; AlSedawy M.; Ramadan M.A.; Amin B.H.; Faid A.H.; Abdelmaksoud H.F.; El-Sayed S.M. Journal: Scientific Reports Publisher: Nature Research Publication Date: 7 September 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 27918 ISSN: 20452322 DOI: 10.1038/s41598-026-65860-3 Scopus: View on Scopus PubMed: 42706305 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Dokmak H.-A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Giza, Egypt; AlSedawy M., Microbiology and Immunology Department, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo, Egypt; Ramadan M.A., Department of Laser Application in Metrology, Photochemistry and Agriculture, National Institute of Laser Enhanced Science (NILES) Cairo University (CU), Giza, Egypt; Amin B.H., The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11787,...
Read more

Corrigendum to ‘Eco-friendly approach for the removal and simultaneous detection of cyanide toxins from drinking and wastewater sources’ [Environ. Pollut. 385 (2025) 127094]

Image
Bibliographic Information Authors: El-Sewify I.M.; Shenashen M.A.; Gomaa H.; Selim M.S.; Akhtar N.; Azzam A.; Mekawy M.; Emran M.Y.; Khairy M.; Shahat A.; Hasan M.; Elmarakbi A.; El-Safty S.A. Journal: Environmental Pollution Publisher: Elsevier Ltd Publication Date: September 2026 Volume / Issue: Volume 405 Article No.: 128412 ISSN: 2697491 DOI: 10.1016/j.envpol.2026.128412 Scopus: View on Scopus PubMed: 42259729 Document Type: Erratum Authors and Affiliations El-Sewify I.M., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan, Chemistry Department, Faculty of Science, Ain Shams University, Abbasia, Cairo, 11566, Egypt; Shenashen M.A., Research Center for Macromolecules and Biomaterials, National Institute for Materials Science (NIMS), 1–2-1 Sengen, Ibaraki-ken, Tsukubashi, 305–0047, Japan; Gomaa H., Research Center for Macromolecules and Biomaterials, Na...
Read more

Multifunctional polycaprolactone-based composite fibers with icariin and glutathione for effective repair of critical-sized bone defects

Image
Bibliographic Information Authors: Yessuf A.M.; Zhang Y.; Sharma B.P.; Wang Y.; Kassa T.S.; Qadir A.; Jinqiu Y.; Mohideen M.M.; Salama A.M.; Wang W.; Zhang Q.; Liu Y. Journal: BMEMat Publisher: John Wiley and Sons Inc Publication Date: 30 July 2026 ISSN: 27517438 DOI: 10.1002/bmm2.70115 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access Authors and Affiliations Yessuf A.M., Key Laboratory of Advanced Functional Polymer Composites, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Zhang Y., Henan Provincial Orthopedic Hospital, Henan, Zhengzhou, China; Sharma B.P., Key Laboratory of Electrochemical Process and Technology of Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Wang Y., Beijing University of Chinese Medicine, Beijing, China; Kassa T.S., Key Laboratory of Advanced Functional Polymer Composites, Col...
Read more