A Multi-Mineral Natural Product Inhibits Liver Tumor Formation in C57BL/6 Mice

Abstract

C57BL/6 mice were maintained for up to 18-months on high-fat and low-fat diets with or without a multi-mineral-supplement derived from the skeletal remains of the red marine algae Lithothamnion calcareum. Numerous grossly observable liver masses were visible in animals on the “western-style” high-fat diet sacrificed at 12 and 18 months. The majority of the masses were in male mice (20 out of 100 males versus 3 out of 100 females; p=0.0002). There were more liver masses in animals on the high-fat diet than on the low-fat diet (15 out of 50 on high-fat versus 5 out of 50 on low-fat; p=0.0254). The multi-mineral supplement reduced the number of liver masses in mice on both diets (3 out of 25 male mice in the low-fat diet group without the supplement versus 1 out of 25 mice with supplement; 12 of 25 male mice in the high-fat diet group without the supplement versus 3 of 25 mice with supplement [p=0.0129]). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas), and 18 pre-neoplastic lesions. Out of 8 hepatocellular carcinomas, 7 were found in unsupplemented diet groups. Steatosis was widely observed in livers with and without grossly observable masses, but the multi-mineral supplement had no effect on the incidence of steatosis or its severity. Taken together, these findings suggest that a multi-mineral-rich natural product can protect mice against neoplastic and pre-neoplastic proliferative liver lesions that may develop in the face of steatosis.

Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles

“…The progression of histological changes seen in NAFLD, including steatohepatitis with formation of regenerative hyperplastic nodules (RH) and/or hepatocellular neoplasms, has been demonstrated in mice fed a high content of saturated fat and excess calories [5,13–15]. In our own previous study, male C57BL/6NCrl male mice (but not female mice) maintained on a HFWD for up to 18 months developed liver tumors at a significantly higher rate and more rapidly than littermates fed a standard rodent chow diet (AIN76A) [13].…”

“…In our own previous study, male C57BL/6NCrl male mice (but not female mice) maintained on a HFWD for up to 18 months developed liver tumors at a significantly higher rate and more rapidly than littermates fed a standard rodent chow diet (AIN76A) [13]. The HFWD is designed to mimic dietary habits prevalent in Western countries [16–18], and contains increased saturated fat and total calories as compared to a typical rodent chow diet.…”

“…In our previous study, male C57BL6/NCrl mice fed a HFWD but supplemented with a calcium-rich, multi-mineral-containing natural product had reduced non-neoplastic and neoplastic liver damage [13]. The current study was intended to separate the effects of calcium from multi-mineral supplementation.…”

“…The current study was intended to separate the effects of calcium from multi-mineral supplementation. Male mice were used since NAFLD is more common in men [33] and this predominance is recapitulated in mouse models [13,34,35]. The C57Bl/6NCrl substrain was chosen since the B6N substrain has demonstrated higher body weight gains, higher percent body fat, and higher liver triglycerides in response to high fat intake than the B6J substrain [36].…”

Suppression of Hepatitis B Virus Production and Inflammatory Response in vitro and in vivo by Mormodica charantia Compound EMCDO

“…There is a growing body of in vitro evidence demonstrating the inhibitory effects of certain natural products on liver cancer cells via various regulatory mechanisms (Aslam et al, 2012). Triterpenes have previously been purified from the bitter melon, and detailed analysis has shown that the compounds consist in the main of cucurbitane-type triterpenoids (Liao et al, 2012).…”