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Protective effects of phloridzin against methotrexate-induced liver toxicity in rats.
Biomed Pharmacother. 2017 Nov; 95:529-535.BP

Abstract

BACKGROUND

Liver is the largest internal organ concerning with metabolism, hormonal balance and clarifying of the toxins. One of the main complications of methotrexate (MTX) therapy was the hepatic injury.

OBJECTIVE

This study was conducted to elucidate the possible protective effects of phloridzin (PHL) against MTX-induced hepatotoxicity as compared to standard agent N-acetylcysteine (NAC).

MATERIALS AND METHODS

Rats were randomly divided into a normal control group, a respective group (PHL 40mg/kg/day orally (p.o.) for 10 consecutive days), a hepatotoxicity control group (MTX 20mg/kg, i.p., once), and three treated groups received NAC (150mg/kg/day; a reference standard), PHL (40mg/kg/day) and PHL (80mg/kg/day) p.o. for 10 consecutive days, at the end of the day 3 of the experiment rats were administered MTX. Assessed biomarkers included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) as liver function parameters, serum tumor necrosis factor-α (TNF-α) and cyclooxygenase-II (COX-II), as inflammatory biomarkers, hepatic total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), glutathione reduced (GSH), nitrite (NO2-), catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) as oxidative stress biomarkers. Furthermore, hepatic caspase-3 expression was assessed. Biochemical and molecular estimations reinforced by histopathological findings.

RESULTS

Rats pre-treated with PHL significantly reduced hepatic injury, evidenced by significant reductions in ALT, AST and LDH, TNF-α and COX-II levels, significant reductions in hepatic NO2- and TBARS levels, and significant elevations in hepatic TAC, GSH, GST, CAT and SOD levels. Additionally, downregulation of hepatic caspase-3 expression. Finally, histopathological results consistent with our previous findings.

CONCLUSION

PHL protects against hepatic injury in rats mainly through mitigation of oxidative stress, inflammation and apoptosis in hepatic tissues and may be promising to alleviate and early treatment of MTX-induced hepatoxicity in man.

Authors+Show Affiliations

Faculty of Pharmacy, Department of Pharmacology & Toxicology, Minia University, Minia 61511, Egypt.Faculty of Pharmacy, Department of Pharmacology & Toxicology, Al-Azhar University, Assiut 71524, Egypt. Electronic address: adelpharma2007@yahoo.com.Faculty of Pharmacy, Department of Pharmacology & Toxicology, Al-Azhar University, Assiut 71524, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28866420

Citation

Khalifa, Mohamed M A., et al. "Protective Effects of Phloridzin Against Methotrexate-induced Liver Toxicity in Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 95, 2017, pp. 529-535.
Khalifa MMA, Bakr AG, Osman AT. Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. Biomed Pharmacother. 2017;95:529-535.
Khalifa, M. M. A., Bakr, A. G., & Osman, A. T. (2017). Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 95, 529-535. https://doi.org/10.1016/j.biopha.2017.08.121
Khalifa MMA, Bakr AG, Osman AT. Protective Effects of Phloridzin Against Methotrexate-induced Liver Toxicity in Rats. Biomed Pharmacother. 2017;95:529-535. PubMed PMID: 28866420.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of phloridzin against methotrexate-induced liver toxicity in rats. AU - Khalifa,Mohamed M A, AU - Bakr,Adel G, AU - Osman,Adel T, Y1 - 2017/09/12/ PY - 2017/05/02/received PY - 2017/08/26/revised PY - 2017/08/28/accepted PY - 2017/9/4/pubmed PY - 2018/6/21/medline PY - 2017/9/4/entrez KW - Caspase-3 KW - Hepatotoxicity KW - Methotrexate KW - Oxidative stress KW - Phloridzin KW - Rats SP - 529 EP - 535 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 95 N2 - BACKGROUND: Liver is the largest internal organ concerning with metabolism, hormonal balance and clarifying of the toxins. One of the main complications of methotrexate (MTX) therapy was the hepatic injury. OBJECTIVE: This study was conducted to elucidate the possible protective effects of phloridzin (PHL) against MTX-induced hepatotoxicity as compared to standard agent N-acetylcysteine (NAC). MATERIALS AND METHODS: Rats were randomly divided into a normal control group, a respective group (PHL 40mg/kg/day orally (p.o.) for 10 consecutive days), a hepatotoxicity control group (MTX 20mg/kg, i.p., once), and three treated groups received NAC (150mg/kg/day; a reference standard), PHL (40mg/kg/day) and PHL (80mg/kg/day) p.o. for 10 consecutive days, at the end of the day 3 of the experiment rats were administered MTX. Assessed biomarkers included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) as liver function parameters, serum tumor necrosis factor-α (TNF-α) and cyclooxygenase-II (COX-II), as inflammatory biomarkers, hepatic total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), glutathione reduced (GSH), nitrite (NO2-), catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) as oxidative stress biomarkers. Furthermore, hepatic caspase-3 expression was assessed. Biochemical and molecular estimations reinforced by histopathological findings. RESULTS: Rats pre-treated with PHL significantly reduced hepatic injury, evidenced by significant reductions in ALT, AST and LDH, TNF-α and COX-II levels, significant reductions in hepatic NO2- and TBARS levels, and significant elevations in hepatic TAC, GSH, GST, CAT and SOD levels. Additionally, downregulation of hepatic caspase-3 expression. Finally, histopathological results consistent with our previous findings. CONCLUSION: PHL protects against hepatic injury in rats mainly through mitigation of oxidative stress, inflammation and apoptosis in hepatic tissues and may be promising to alleviate and early treatment of MTX-induced hepatoxicity in man. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28866420/Protective_effects_of_phloridzin_against_methotrexate_induced_liver_toxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)32128-5 DB - PRIME DP - Unbound Medicine ER -