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Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats

Hossam Ebaid12*, Samir AE Bashandy13, Ibrahim M Alhazza14, Ahmed Rady1 and Sultan El-Shehry1

Author Affiliations

1 Department of Zoology, College of Science, King Saud University, KSA, P.O.Box, 2455, Riyadh, 11451, Saudi Arabia

2 Department of Zoology, College of Science, El-Minia University, El-Minia, Egypt

3 Department of Pharmacology, National Research Center, Cairo, Egypt

4 Fetal Programming of Disease Research Chair, King Saud University, KSA, Riyadh, Saudi Arabia

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Nutrition & Metabolism 2013, 10:20  doi:10.1186/1743-7075-10-20

Published: 3 February 2013


This study investigated the protective effects of melatonin and folic acid against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Oxidative stress, liver function, liver histopathology and serum lipid levels were evaluated. The levels of protein kinase B (Akt1), interferon gamma (IFN-γ), programmed cell death-receptor (Fas) and Tumor necrosis factor-alpha (TNF-α) mRNA expression were analyzed. CCl4 significantly elevated the levels of lipid peroxidation (MDA), cholesterol, LDL, triglycerides, bilirubin and urea. In addition, CCl4 was found to significantly suppress the activity of both catalase and glutathione (GSH) and decrease the levels of serum total protein and HDL-cholesterol. All of these parameters were restored to their normal levels by treatment with melatonin, folic acid or their combination. An improvement of the general hepatic architecture was observed in rats that were treated with the combination of melatonin and folic acid along with CCl4. Furthermore, the CCl4-induced upregulation of TNF-α and Fas mRNA expression was significantly restored by the three treatments. Melatonin, folic acid or their combination also restored the baseline levels of IFN-γ and Akt1 mRNA expression. The combination of melatonin and folic acid exhibited ability to reduce the markers of liver injury induced by CCl4 and restore the oxidative stability, the level of inflammatory cytokines, the lipid profile and the cell survival Akt1 signals.

Hepatic injury-markers; Melatonin; Folic acid; Akt1; Oxidative stress; Anti-inflammatory effects