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BackgroundNon-alcoholic fatty liver disease (NAFLD) is defined as a spectrum of conditions ranging from hepatocellular steatosis to steatohepatitis and fibrosis, progressing to cirrhosis, which occur in the absence of excessive alcohol use. Several animal models capture aspects of NAFLD but are limited either in their representation of the disease stages or use for development of therapeutics due to the extended periods of time required to develop full histological features.MethodsHere, we report the development of a novel rat model for NAFLD that addresses some of these limitations. We used a fast food diet (FFD) and a CCl4 micro dose (0.5 ml/kg B.wt) for 8 weeks in Wistar rats. Serological analyses, gene expression profiling and liver histology studies were conducted to investigate the development of steatosis, steatohepatitis and fibrosis in the FFD-CCl4 model when compared to the individual effects of a FFD or a micro dose of CCl4 in rats.ResultsThe serum biochemical profile of the FFD-CCl4 model showed an increase in liver injury and fibrosis. This was also accompanied by a significant increase in liver triglycerides (TG), inflammation and oxidative stress. Importantly, we observed extensive fibrosis confirmed by: i) increased gene expression of fibrosis markers and, ii) moderate to severe collagen deposition seen as perisinusoidal and bridging fibrosis using H&E, Trichome and Sirius Red staining.ConclusionsIn summary, we find that the FFD-CCl4 rat model developed NAFLD histological features including, steatosis, inflammation and fibrosis in 8 weeks showing promise as a model that can be used to develop NAFLD therapeutics and liver anti-fibrotics.

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Background: Use of biomarkers particularly under in vivo condition is of importance in risk assessment. This study is proposed to identify the in vivo antigenotoxic potential using dominant lethal mutation test in B(a)P exposed, turmeric fed animals and evaluate the role of turmeric in counteracting the germ cell mutations. Methods: Twenty four male mice were taken and divided into 4 groups each group containing 6 mice/group. The first and second group received stock diet (control) while the third and fourth groups received 5% turmeric diet for a period of one month. At the end of feeding period, second and fourth group received a single dose of benzo(a)pyrene 1mg/mouse intraperitoneally. After 1 week each male mouse was mated to 3 female mice at 1,4, 8 and 12 week intervals. On 13th day from mid point of mating, the females were sacrificed and live and dead embryos were counted to study the pre and post implantation loss of embryos. The differences in the frequencies of pre and post implant deaths were done by comparing treated with control group at 4-time periods by analysis of variance (ANOVA) and chi-square test which is used to compare treatment group and positive control with negative control. Results: Feeding of 5% turmeric and treatment with a single dose of B(a)P did not show any significant effect on the mutagenic index or the frequency of pregnancy in treated groups compared with control. There was no apparent induction of dominant lethal mutations in B(a)P or B(a)P+Turmeric treated groups. No post implantation dominant lethal effects produced by B(a)P could be detected in this study. The induction of B(a)P and treatment with turmeric did not influence the dominant lethal test. Conclusion: B(a)P did not produce a significant increase in the dominant lethal mutations. Turmeric also did not give any positive response and may be considered as non-mutagenic. The negative result suggests that under the conditions of the test the test substance may not be genotoxic in the germ cell of the treated sex of the test species.