TY - JOUR
T1 - Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver
T2 - An experimental approach
AU - Ali, Nemat
AU - Rashid, Summya
AU - Nafees, Sana
AU - Hasan, Syed Kazim
AU - Shahid, Ayaz
AU - Majed, Ferial
AU - Sultana, Sarwat
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/6/25
Y1 - 2017/6/25
N2 - Methotrexate (MTX) is a drug which is used to treat different types of cancers but hepatotoxicity limits its clinical use. Chlorogenic acid (CGA) is one of the most abundant naturally occurring polyphenols in the human diet. Here, we assessed the effect of CGA against MTX-induced hepatotoxicity and investigated the underlying possible mechanisms in Wistar Rats. Rats were pre-treated with CGA (50 or 100 mg kg/b.w) and administered a single dose of MTX (20 mg/kg, b.w.). MTX caused hepatotoxicity as evidenced by significant increase in serum toxicity markers, histopathological changes. decreased activities of anti-oxidant armory (SOD, CAT, GPx, GR) and GSH content. MTX significantly causes upregulation of iNOS, Cox-2, Bax and downregulation of Bcl-2 expressions, it causes higher caspase 3, 9 activities. However CGA pretreatment alleviates the hepatotoxicity by decreasing the oxidative stress. CGA inhibited Cox-2, iNOS, Bax, Bcl-2 and Caspases 3, 9 mediated inflammation and apoptosis, and improve the histology induced by MTX. Thus, these findings demonstrated the hepatoprotective nature of CGA by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in hepatic tissue. These results imply that CGA has perfective effect against MTX-induced liver injury. Hence CGA supplementation might be helpful in abrogation of MTX toxicity.
AB - Methotrexate (MTX) is a drug which is used to treat different types of cancers but hepatotoxicity limits its clinical use. Chlorogenic acid (CGA) is one of the most abundant naturally occurring polyphenols in the human diet. Here, we assessed the effect of CGA against MTX-induced hepatotoxicity and investigated the underlying possible mechanisms in Wistar Rats. Rats were pre-treated with CGA (50 or 100 mg kg/b.w) and administered a single dose of MTX (20 mg/kg, b.w.). MTX caused hepatotoxicity as evidenced by significant increase in serum toxicity markers, histopathological changes. decreased activities of anti-oxidant armory (SOD, CAT, GPx, GR) and GSH content. MTX significantly causes upregulation of iNOS, Cox-2, Bax and downregulation of Bcl-2 expressions, it causes higher caspase 3, 9 activities. However CGA pretreatment alleviates the hepatotoxicity by decreasing the oxidative stress. CGA inhibited Cox-2, iNOS, Bax, Bcl-2 and Caspases 3, 9 mediated inflammation and apoptosis, and improve the histology induced by MTX. Thus, these findings demonstrated the hepatoprotective nature of CGA by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in hepatic tissue. These results imply that CGA has perfective effect against MTX-induced liver injury. Hence CGA supplementation might be helpful in abrogation of MTX toxicity.
KW - Antioxidants
KW - Apoptosis
KW - Hepatotoxicity
KW - MTX
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85019448174&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2017.05.002
DO - 10.1016/j.cbi.2017.05.002
M3 - Article
C2 - 28479099
AN - SCOPUS:85019448174
SN - 0009-2797
VL - 272
SP - 80
EP - 91
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -
