Combination Treatment of Omega-3 Fatty Acids and Vitamin C Exhibited Promising Therapeutic Effect against Oxidative Impairment of the Liver in Methotrexate-Intoxicated Mice.
Drug-induced liver injury (DILI) is the main cause of liver damage mediated by the excretion of toxic active drug metabolites. Omega-3 fatty acids and vitamin C have potent antioxidant, anti-inflammatory, and antiapoptotic effects that could offer protection against oxidative stress and liver damage...
| Publicado en: | BioMed Research International pp. 1 - 12 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
4/20/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=156418968&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 156418968 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 4/20/2022 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 156418968 156418968 156418968 10.1155/2022/4122166 156418968 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Combination Treatment of Omega-3 Fatty Acids and Vitamin C Exhibited Promising Therapeutic Effect against Oxidative Impairment of the Liver in Methotrexate-Intoxicated Mice. aug: au: Alorabi, Mohammed Mohammed, Doha Saad Mostafa-Hedeab, Gomaa El-Sherbeni, Suzy A. Negm, Walaa A. Mohammed, Ali Ismail A. Al-kuraishy, Hayder M. Nasreldin, Nani Alotaibi, Saqer S. Lawal, Bashir Batiha, Gaber El-Saber Conte-Junior, Carlos Adam affil: Department of Biotechnology, College of Sciences, Taif University, P.O.Box 11099, Taif 21944, Saudi Arabia sug: subj: Oxidative Stress Drug Effects Liver Diseases Drug Therapy Fatty Acids, omega-3 Pharmacodynamics Ascorbic Acid Pharmacodynamics Methotrexate Poisoning Liver Diseases Chemically Induced Models, Biological Drug Therapy, Combination Animal Studies Mice Methotrexate Adverse Effects Treatment Outcomes Evaluation Normal Saline Administration and Dosage Fatty Acids, omega-3 Administration and Dosage Ascorbic Acid Administration and Dosage Biological Markers Blood Metabolic Networks and Pathways Dose-Response Relationship, Drug Molecular Docking Simulation Liver Diseases Pathology Histology ab: Drug-induced liver injury (DILI) is the main cause of liver damage mediated by the excretion of toxic active drug metabolites. Omega-3 fatty acids and vitamin C have potent antioxidant, anti-inflammatory, and antiapoptotic effects that could offer protection against oxidative stress and liver damage. This study evaluated the hepatoprotective effect of omega-3 and vitamin C alone as well as in a combined form in methotrexate- (MTX-) induced acute liver injury in mice. Male ICR mice of seven groups (7 mice per group) were used. Groups 1 (control group) and 2 (MTX) received 0.9% saline/day (po) for 9 days. Groups 3 and 4 received 100 and 200 mg/kg bw/day omega-3 (po), respectively, for 9 days. Groups 5 and 6 received 100 and 200 mg/kg bw/day vitamin C (po), respectively, for 9 days, while group 7 received omega-3 (100 mg/kg bw/day) and vitamin C (100 mg/kg bw/day) (po) for 9 days. All animals in groups 2 to 7 received 20 mg/kg/day MTX (I.P.) once on the 10th day. Our results revealed that MTX significantly induced the elevation of transaminases, alkaline phosphates (ALP), lactate dehydrogenase (LDH), and malonaldehyde (MDA) while depleting the levels of superoxide dismutase (SOD) and glutathione (GSH) when compared to the control group. Treatment with omega-3 fatty acids or vitamin C significantly attenuated the antioxidants and biochemical alterations in a dose-independent manner. Our molecular docking study of ligand-receptor interaction revealed that both ascorbic acid and omega-3 docked well to the binding cavity of LDH with high binding affinities of –5.20 and –4.50 kcal/mol, respectively. The histopathological features were also improved by treatment with omega-3 and vitamin C. The combined form of omega-3 and vitamin C showed a remarkable improvement in the liver enzymes, oxidative stress biomarkers, and the histopathological architecture of the mice. Conclusively, the combination of omega-3 and vitamin C demonstrated a synergistic therapeutic effect against MTX-intoxicated mice, hence representing a potential novel strategy for the management of drug-induced liver disorders. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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