Published online May 15, 2017. doi: 10.4291/wjgp.v8.i2.67
Peer-review started: September 1, 2016
First decision: October 31, 2016
Revised: December 1, 2016
Accepted: February 28, 2017
Article in press: March 2, 2017
Published online: May 15, 2017
To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe-/- high calorie diet model of steatohepatitis.
Hfe-/- C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways.
Hfe-/- mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease (NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the mRNA expression of AdipoR2, Ppar-α, Cpt1a, Nrf-1 and Tfb2m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe-/- mice.
Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.
Core tip: The high prevalence of obesity and the metabolic syndrome suggests that many patients with liver disease of varying etiologies will have co-existent non-alcoholic fatty liver disease. Our model of co-toxic liver disease incorporates increased hepatic iron in combination with steatosis and was associated with necroinflammation and early hepatic fibrosis. Because of the beneficial effect of combination therapy, we believe vitamin E and curcumin should be investigated in other animal models of non-alcoholic steatohepatitis. Should beneficial effects be demonstrated, combination treatment with the development of appropriate dosing strategies could be rapidly moved to human studies allowing for an effective treatment strategy.