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Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats.
Biomed Pharmacother. 2018 Jan; 97:233-239.BP

Abstract

Hepatotoxicity is one of the major side effects of methotrexate (MTX), which restricts the clinical use of this drug. Berberine (BBR) is a natural compound with multiple pharmacological activities such as antioxidant, antiapoptotic and anti-inflammatory effects. In this study, the effect of BBR on MTX-induced hepatotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups. Rats were pretreated with BBR orally with dose of 100mg/kg for 10 consecutive days and MTX (20mg/kg, intraperitoneally) was administrated on the 9th day. Then on day 11, blood samples were collected to determine serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The extracted livers were used for histological examination, biochemical assays and real time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activities were assessed in hepatic tissue. In addition, the expression of SOD and PGx was measured using real-time PCR method in hepatic tissue. Results showed that MTX administration significantly increases AST, ALT and ALP levels (all p<0.001). It also, increases MDA, PC, NO levels and MPO activity (p<0.001, p<0.01, p<0.05 and p<0.01 respectively). Moreover, MTX decreases hepatic GSH level, SOD, GPx and CAT activities (all p<0.001). Pre-treatment with BBR for 10days prevented some of these changes. Serum levels of AST and ALT decreased (all p<0.001). Hepatic MDA level decreased (p<0.001) and GSH level as well as GPx activity increased (p<0.05 and p<0.01 respectively). Our results indicated that BBR might be useful for prevention of the hepatotoxicity induced by MTX via ameliorative effects on biochemical and oxidative stress indices.

Authors+Show Affiliations

Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.Student Research Committee, Esfarayen Faculty of Medical Sciences, Esfarayen, Iran.Zahedan University of Medical Sciences, Zahedan, Iran.Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: gmehdi_787@yahoo.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29091871

Citation

Mehrzadi, Saeed, et al. "Hepatoprotective Effect of Berberine Against Methotrexate Induced Liver Toxicity in Rats." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 97, 2018, pp. 233-239.
Mehrzadi S, Fatemi I, Esmaeilizadeh M, et al. Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomed Pharmacother. 2018;97:233-239.
Mehrzadi, S., Fatemi, I., Esmaeilizadeh, M., Ghaznavi, H., Kalantar, H., & Goudarzi, M. (2018). Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 97, 233-239. https://doi.org/10.1016/j.biopha.2017.10.113
Mehrzadi S, et al. Hepatoprotective Effect of Berberine Against Methotrexate Induced Liver Toxicity in Rats. Biomed Pharmacother. 2018;97:233-239. PubMed PMID: 29091871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatoprotective effect of berberine against methotrexate induced liver toxicity in rats. AU - Mehrzadi,Saeed, AU - Fatemi,Iman, AU - Esmaeilizadeh,Mahdi, AU - Ghaznavi,Habib, AU - Kalantar,Hadi, AU - Goudarzi,Mehdi, Y1 - 2017/11/06/ PY - 2017/08/11/received PY - 2017/10/17/revised PY - 2017/10/21/accepted PY - 2017/11/2/pubmed PY - 2018/8/4/medline PY - 2017/11/2/entrez KW - Antioxidants KW - Berberine KW - Hepatotoxicity KW - Methotrexate KW - Rat SP - 233 EP - 239 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 97 N2 - Hepatotoxicity is one of the major side effects of methotrexate (MTX), which restricts the clinical use of this drug. Berberine (BBR) is a natural compound with multiple pharmacological activities such as antioxidant, antiapoptotic and anti-inflammatory effects. In this study, the effect of BBR on MTX-induced hepatotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups. Rats were pretreated with BBR orally with dose of 100mg/kg for 10 consecutive days and MTX (20mg/kg, intraperitoneally) was administrated on the 9th day. Then on day 11, blood samples were collected to determine serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The extracted livers were used for histological examination, biochemical assays and real time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activities were assessed in hepatic tissue. In addition, the expression of SOD and PGx was measured using real-time PCR method in hepatic tissue. Results showed that MTX administration significantly increases AST, ALT and ALP levels (all p<0.001). It also, increases MDA, PC, NO levels and MPO activity (p<0.001, p<0.01, p<0.05 and p<0.01 respectively). Moreover, MTX decreases hepatic GSH level, SOD, GPx and CAT activities (all p<0.001). Pre-treatment with BBR for 10days prevented some of these changes. Serum levels of AST and ALT decreased (all p<0.001). Hepatic MDA level decreased (p<0.001) and GSH level as well as GPx activity increased (p<0.05 and p<0.01 respectively). Our results indicated that BBR might be useful for prevention of the hepatotoxicity induced by MTX via ameliorative effects on biochemical and oxidative stress indices. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29091871/Hepatoprotective_effect_of_berberine_against_methotrexate_induced_liver_toxicity_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)34088-X DB - PRIME DP - Unbound Medicine ER -