Understanding tissue biodistribution and clearance of zinc oxide nanoparticles (ZnO-NPs) is necessary for its risk assessment. Both fed and intraperitoneally injected ZnO-NPs (2.5 g/kg) were absorbed into circulation (within 30 min post-dosing), then biodistributed to the liver, spleen, and kidney. Intraperitoneally injected ZnO-NPs remained in serum for 72 h and could more effectively spread to the heart, lung, and testes, whereas the clearance for fed ZnO-NPs in serum began 6 h after oral administration. Compared with zinc oxide microparticles (ZnO-MPs), ZnO-NPs exhibited much higher absorptivity and tissue biodistribution in fed treatment. A greater fraction of fed ZnO-NPs localised in the liver resulted in transient histopathological lesions. However, superoxide generation and cytotoxicity were showed in vitro treatment with ZnO-NPs (above 20 μg/mL). Considering both in vitro and in vivo data, the ZnO-NPs induced acute liver toxicity which was in compliance with its absorption, biodistribution, and clearance.

Certain nondigestible oligosaccharides can be selectively utilized by probiotics and reduce the risk of colon cancer. However, the inhibitory effects of xylooligosaccharides (XOS) on colon cancer are not well documented. This study evaluated the effects of xylooligosaccharides and fructooligosaccharides (FOS) on the alteration of cecal microbiota, cecal pH, cecal weight, and serum lipid levels, and also their inhibitory effect on precancerous colon lesions in male Sprague-Dawley rats. The rats were randomly assigned to 4 groups: control, treatment with 1,2-dimethylhydrazine (DMH) [15 mg/(kg body wt · wk) for 2 wk], treatment with DMH + 60 g XOS/kg diet, and treatment with DMH + 60 g FOS/kg diet. Rats were fed the experimental diets for 35 d, beginning 1wk after the second dose of DMH. Both XOS and FOS markedly decreased the cecal pH and serum triglyceride concentration, and increased the total cecal weight and bifidobacteria population. XOS had a greater effect on the bacterial population than did FOS. Moreover, both XOS and FOS markedly reduced the number of aberrant crypt foci in the colon of DMH-treated rats. These results suggest that XOS and FOS dietary supplementation may be beneficial to gastrointestinal health, and indicate that XOS is more effective than FOS.

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely ¹H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a ¹H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help our further understanding of the effect of GA in hepatosteatosis mice.

Rapamycin (RAPA), an immunosuprpressive drug used extensively to prevent graft rejection in transplant patients, has been reported to inhibit adipogenesis in vitro. In this study, we investigated the anti-obesity effects of RAPA in C57BL/6J mice on a high-fat diet (HFD). Mice treated with RAPA (2 mg/kg per week for 16 weeks) had reduced body weight and epididymal fat pads/body weight, reduced daily food efficiency, and lower serum leptin and insulin levels compared with the HFD control mice. However, RAPA-treated mice were hyperphagic, demonstrating an increase in food intake. Dissection of RAPA-treated mice revealed a marked reduction in fatty liver scores, average fat cell size, and percentage of large adipocytes of retroperitoneal and epididymal white adipose tissue (RWAT and EWAT), compared to the HFD control mice. These results suggest that RAPA prevented the effect of the high-fat diet on the rate of accretion in body weight via reducing lipid accumulation, despite greater food intake. It is likely that RAPA may serve as a potential strategy for body weight control and/or anti-obesity therapy.