cryptoxanthins and Liver-Cirrhosis

Since the incidence of liver cancer is increasing in the world, it is valuable to develop an effective method for its prevention. Various phytochemicals have been shown to suppress liver carcinogenesis in experimental studies. Using these phytochemicals, a clinical trial was conducted. Combination of carotenoids and myo-inositol was found to prevent hepatocellular carcinoma development in patients with chronic viral hepatitis and cirrhosis.

Topics: alpha-Tocopherol; Animals; Anticarcinogenic Agents; beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Cryptoxanthins; Dietary Supplements; Hepatitis, Viral, Human; Humans; Inositol; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Neoplasms; Lycopene; Male; Mice; Mice, Inbred C3H; Tumor Burden; Xanthophylls

Excessive hepatic lipid accumulation promotes macrophages/Kupffer cells activation, resulting in exacerbation of insulin resistance and progression of nonalcoholic steatohepatitis (NASH). However, few promising treatment modalities target lipotoxicity-mediated hepatic activation/polarization of macrophages for NASH. Recent epidemiological surveys showed that serum β-cryptoxanthin, an antioxidant carotenoid, was inversely associated with the risks of insulin resistance and liver dysfunction. In the present study, we first showed that β-cryptoxanthin administration ameliorated hepatic steatosis in high-fat diet-induced obese mice. Next, we investigated the preventative and therapeutic effects of β-cryptoxanthin using a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat (CL) diet. After 12 weeks of CL diet feeding, β-cryptoxanthin administration attenuated insulin resistance and excessive hepatic lipid accumulation and peroxidation, with increases in M1-type macrophages/Kupffer cells and activated stellate cells, and fibrosis in CL diet-induced NASH. Comprehensive gene expression analysis showed that β-cryptoxanthin down-regulated macrophage activation signal-related genes significantly without affecting most lipid metabolism-related genes in the liver. Importantly, flow cytometry analysis revealed that, on a CL diet, β-cryptoxanthin caused a predominance of M2 over M1 macrophage populations, in addition to reducing total hepatic macrophage and T-cell contents. In parallel, β-cryptoxanthin decreased lipopolysaccharide-induced M1 marker mRNA expression in peritoneal macrophages, whereas it augmented IL-4-induced M2 marker mRNA expression, in a dose-dependent manner. Moreover, β-cryptoxanthin reversed steatosis, inflammation, and fibrosis progression in preexisting NASH in mice. In conclusion, β-cryptoxanthin prevents and reverses insulin resistance and steatohepatitis, at least in part, through an M2-dominant shift in macrophages/Kupffer cells in a lipotoxic model of NASH.

Topics: Animals; Antioxidants; Cryptoxanthins; Dietary Fats; Glucose; Hepatic Stellate Cells; Homeostasis; Insulin Resistance; Kupffer Cells; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity

The authors consider two groups of patients with overt sporadic porphyria cutanea tarda (PCT) from different continents, with the aim of evaluating the possible impairment of the liposoluble antioxidative system, given the possible synergic effect of porphyrins and iron in promoting oxidative cellular damage. Twenty-three Italian outpatients with overt sporadic PCT and 11 outpatients with PCT from Buenos Aires (Argentina) were matched with 60 patients with liver cirrhosis and 52 healthy Italian controls. Serum levels of alpha- and beta-carotene, cryptoxanthin, zeaxanthin, lutein, lycopene, retinol and alpha-tocopherol were detected by a high-performance liquid chromatographic technique devised in our laboratory, which afforded an accurate and simultaneous resolution of all these compounds. The results point to a significant reduction in plasma levels of alpha- and beta-carotene in both the PCT populations with respect not only to controls, but also to the cirrhotic population, which had more severe liver damage. Moreover, other carotenoids with proven antioxidative properties, like cryptoxanthin and lycopene, are greatly reduced in our PCT populations. This confirms the suggested synergic effect of iron and porphyrins in the oxidative intracellular damage with consequent depletion of antioxidative liposoluble molecules.

Topics: Alkaline Phosphatase; Analysis of Variance; Antioxidants; Argentina; beta Carotene; Bilirubin; Carotenoids; Case-Control Studies; Cholesterol; Creatinine; Cryptoxanthins; Female; Humans; Italy; Liver Cirrhosis; Lutein; Lycopene; Male; Middle Aged; Porphyria Cutanea Tarda; Prothrombin; Reference Values; Serum Albumin; Vitamin A; Vitamins; Xanthophylls; Zeaxanthins