Effects of compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid on relative metabolic enzymes and various biochemical indices in Wistar rats with isoniazid-induced liver injury.

Publisher: Elsevier Science Country of Publication: England NLM ID: 8309336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-264X (Electronic) Linking ISSN: 07317085 NLM ISO Abbreviation: J Pharm Biomed Anal Subsets: MEDLINE

Publication: <2006->: London : Elsevier Science
Original Publication: Oxford ; New York : Pergamon Press, c1983-

Isoniazid*/toxicity ; Rats, Wistar* ; Chemical and Drug Induced Liver Injury*/prevention & control ; Chemical and Drug Induced Liver Injury*/drug therapy ; Chemical and Drug Induced Liver Injury*/metabolism ; Chemical and Drug Induced Liver Injury*/etiology ; Liver*/drug effects ; Liver*/metabolism ; Liver*/pathology ; Antitubercular Agents*/toxicity; Animals ; Rats ; Male ; Orchidaceae/chemistry ; Cytokines/metabolism ; Plant Extracts/pharmacology ; Plant Extracts/administration & dosage ; Tandem Mass Spectrometry/methods ; Administration, Oral

Isoniazid (INH) is the first-line anti-tuberculosis drug in clinical practice, and its main adverse effect is drug-induced liver injury (DILI). This study aimed to investigate the hepatoprotective effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid (CAROL) and to provide a new strategy for the search of potential drugs against INH-induced liver injury in Wistar rats. Animal experiment was based on INH (100 mg/kg) induced liver injury to explore the intervention effects of CAROL at doses of 1.35, 2.70, and 5.40 mL/kg. LC-QTOF-MS/MS was used to identify hepatoprotective components in CAROL and its' exposed components in rat serum. The hepatoprotective effect of CAROL was evaluated by pathological observation of rat liver tissue and changes in levels of biochemical indices and cytokines in serum or liver tissue. Of the 58 hepatoprotective components identified, 15 were detected in the serum of rats with liver-injured treated by high-dose CAROL. Results of animal experiments showed that the levels of various biochemical indexes and cytokines were significantly reversed with CAROL intervention. In particular, the expression level of cytokeratin-18 and high-mobility group box 1, as specific and sensitive indicators of DILI, was significantly reduced in the serum of rats with CAROL intervention compared with the INH model group. The same reversal was observed in the levels of TBIL, ALP, ALT, and AST in serum, as well as in the levels of TNF-α, IL-6, SOD, and MDA in liver tissue. For INH-metabolizing enzymes, an evident expression inhibition was observed in N-acetyltransferase 2 and glutathione S-transferases with CAROL intervention, which may be the key to controlling INH hepatotoxicity. CAROL has a favorable hepatoprotective effect on INH-induced liver injury. This study takes the first step in studying the hepatoprotective mechanism of CAROL against INH hepatotoxicity and provides reference for wider clinical applications.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could appear to have influenced the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)

Keywords: Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid; Glutathione S-transferases; Hepatoprotective; Isoniazid-induced liver injury; N-acetyltransferase 2

V83O1VOZ8L (Isoniazid)
0 (Antitubercular Agents)
0 (Cytokines)
0 (Plant Extracts)

Date Created: 20240627 Date Completed: 20240718 Latest Revision: 20240718

20240719

10.1016/j.jpba.2024.116249

38936169