TY - JOUR
T1 - Reducing power and iron chelating property of Terminalia chebula (Retz.) alleviates iron induced liver toxicity in mice
AU - Sarkar, Rhitajit
AU - Hazra, Bibhabasu
AU - Mandal, Nripendranath
N1 - Funding Information:
Mr. Bibhabasu Hazra is grateful to Council of Scientific and Industrial Research (CSIR), Govt. of India for the support of fellowship. Cipla Ltd., Kolkata, India is acknowledged for providing desirox as reference iron chelating drug for this study. The authors would also like to thank Mr. Ranjit K. Das and Mr. Pradip K. Mallik for technical assistance in sample preparation, handling of lab wares and animals in experimental procedures.
PY - 2012/8/31
Y1 - 2012/8/31
N2 - Background: The 70% methanol extract of Terminalia chebula Retz. fruit (TCME) was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice.Methods: The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound). Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied.Results: In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p.) caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP) and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract also showed potential activity for reductive release of ferritin iron.Conclusions: These findings suggest that Terminalia chebula extract may contain active substances capable of lessening iron overload induced toxicity, and hence possibly be useful as iron chelating drug for iron overload diseases.
AB - Background: The 70% methanol extract of Terminalia chebula Retz. fruit (TCME) was investigated for its in vitro iron chelating property and in vivo ameliorating effect on hepatic injury of iron overloaded mice.Methods: The effect of fruit extract on Fe2+-ferrozine complex formation and Fe2+ mediated pUC-18 DNA breakdown was studied in order to find the in vitro iron chelating activity. Thirty-six Swiss Albino mice were divided into six groups of: blank, patient control and treated with 50, 100, 200 mg/kg b.w. of TCME and desirox (standard iron chelator drug with Deferasirox as parent compound). Evaluations were made for serum markers of hepatic damage, antioxidant enzyme, lipid per oxidation and liver fibrosis levels. The reductive release of ferritin iron by the extract was further studied.Results: In vitro results showed considerable iron chelation with IC50 of 27.19 ± 2.80 μg/ml, and a significant DNA protection with [P]50 of 1.07 ± 0.03 μg/ml along with about 86% retention of supercoiled DNA. Iron-dextran injection (i.p.) caused significant increase in the levels of the serum enzymes, viz., alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP) and Bilirubin, which were subsequently lowered by oral administration of 200 mg/kg b.w. dose of the fruit extract by 81.5%, 105.88%, 188.08% and 128.31%, respectively. Similarly, treatment with the same dose of the extract was shown to alleviate the reduced levels of liver antioxidant enzyme superoxide dismutase, catalase, glutathione S-transferase and non-enzymatic reduced glutathione, by 49.8%, 53.5%, 35.4% and 11% respectively, in comparison to the iron overloaded mice. At the same time, the fruit extract effectively lowered the iron-overload induced raised levels of lipid per oxidation, protein carbonyl, hydroxyproline and liver iron by 49%, 67%, 67% and 26%, respectively, with oral treatment of 200 mg/kg b.w. dose of TCME. The fruit extract also showed potential activity for reductive release of ferritin iron.Conclusions: These findings suggest that Terminalia chebula extract may contain active substances capable of lessening iron overload induced toxicity, and hence possibly be useful as iron chelating drug for iron overload diseases.
UR - http://www.scopus.com/inward/record.url?scp=84865573878&partnerID=8YFLogxK
U2 - 10.1186/1472-6882-12-144
DO - 10.1186/1472-6882-12-144
M3 - Article
C2 - 22938047
AN - SCOPUS:84865573878
SN - 1472-6882
VL - 12
JO - BMC Complementary and Alternative Medicine
JF - BMC Complementary and Alternative Medicine
M1 - 1108
ER -