Premium
L‐Carnitine Attenuates Doxorubicin‐Induced hepatotoxicity Through Antioxidant Signaling
Author(s) -
ALSHABANAH OTHMAN A,
SayedAhmed Mohamed M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1018.6
Subject(s) - carnitine , superoxide dismutase , doxorubicin , glutathione , chemistry , catalase , oxidative stress , glutathione peroxidase , antioxidant , nitric oxide , pharmacology , thiobarbituric acid , endocrinology , saline , medicine , enzyme , biochemistry , lipid peroxidation , biology , chemotherapy
This study examined the mechanism whereby carnitine supplementation attenuates doxorubicin‐induced hepatotoxicity in rats. Male Wistar albino rats were divided into six groups: Rats in group 1 were injected I.P. with normal saline and served as control; rats in group 2, 3 and 4 were injected every other day with doxorubicin (3 mg/kg, i.p.), to obtain treatments with cumulative doses of 6, 12, and 18 mg/kg. Rats in the fifth group were injected with L‐carnitine (200 mg/kg, i.p.) for 10 consecutive plus a cumulative dose of doxorubicin (18 mg/kg). Administration of doxorubicin resulted in a significant dose‐dependent increase in serum markers of liver function, and tissue levels of thiobarbituric acid reactive substances, nitric oxide production, and protein carbonyl content. Moreover, doxorubicin significantly decreased gene expression and activity of superoxide dismutase, glutathione peroxidase, glutathione‐s‐transferase, and catalase in liver tissues. Interestingly, L‐carnitine supplementation completely reversed the biochemical and gene expression levels induced by doxorubicin to the control values. In conclusion, data from this study suggest that L‐carnitine supplementation prevents the development of DOX‐induced hepatocellular damage by decreasing oxidative stress and preserving both the activity and gene expression levels of antioxidant enzymes.