Effect of the oil from the fatty tissues of Crocodylus siamensis on gut microbiome diversity and metabolism in mice.

Dietary fat can alter host metabolism and gut microbial composition. Crocodile oil (CO) was extracted from the fatty tissues of Crocodylus siamensis. CO, rich in monounsaturated- and polyunsaturated fatty acids, has been reported to reduce inflammation, counter toxification, and improve energy metabolism. The aim of this study was to investigate the effect of CO on gut microbiota (GM) in laboratory mice as well as the accompanying metabolic changes in the animals. Forty-five C57BL/6 male mice were randomly divided into five groups and orally administrated either sterile water (control [C]); 1 or 3% (v/w) CO (CO-low [CO-L] and CO-high [CO-H], respectively); or 1 or 3% (v/w) palm oil (PO-low and PO-high, respectively) for 11 weeks. Body weight gain, food intake, energy intake, blood glucose levels, and blood lipid profiles were determined. Samples from colon tissue were collected and the 16S rRNA genes were pyrosequenced to clarify GM analyses. The results showed that there were no differences in body weight and blood glucose levels. Food intake by the mice in the CO-L and CO-H groups was statistically significantly less when compared to that by the animals in the C group. However, neither CO treatment had a statistically significant effect on calorie intake when compared to the controls. The CO-H exhibited a significant increase in serum total cholesterol and low-density lipoprotein but showed a downward trend in triglyceride levels compared to the control. The GM analyses revealed that both CO treatments have no significant influence on bacterial diversity and relative abundance at the phylum level, whereas increases of Choa1 and abundance-based coverage estimator indexes, distinct ß-diversity, and Proteobacteria abundance were observed in the PO-high group compared with the C group. Furthermore, the abundance of Azospirillum thiophilum and Romboutsia ilealis was significantly higher in the CO-L and CO-H groups which could be associated with energy metabolic activity. Thus, CO may be an alternative fat source for preserving host metabolism and gut flora.

The first study on the effect of crocodile oil from Crocodylus siamensis on hepatic mitochondrial function for energy homeostasis in rats.

Background and Aim: Consumption of fatty acids (FA) can alter hepatic energy metabolism and mitochondrial function in the liver. Crocodile oil (CO) is rich in mono-and polyunsaturated FAs, which have natural anti-inflammatory and healing properties. In rat livers, we investigated the effect of CO on mitochondrial function for energy homeostasis. Materials and Methods: Twenty-one male Sprague-Dawley rats were divided into three groups at random. Group 1 rats were given sterile water (RO), Group 2 rats were given CO (3% v/w), and Group 3 rats were given palm oil (PO) (3% v/w). For 7 weeks, rats were given sterile water, CO, and PO orally. The researchers looked at body weight, food intake, liver weight, energy intake, blood lipid profiles, and mitochondria-targeted metabolites in the liver. The liver's histopathology, mitochondrial architecture, and hydrolase domain containing 3 (HDHD3) protein expression in liver mitochondria were studied. Results: Body weight, liver weight, liver index, dietary energy intake, and serum lipid profiles were all unaffected by CO treatment. The CO group consumed significantly less food than the RO group. The CO group also had significantly higher levels of oxaloacetate and malate than the PO group. CO treatment significantly ameliorated hepatic steatosis, as evidenced by a greater decrease in the total surface area of lipid particles than PO treatment. CO administration preserved mitochondrial morphology in the liver by upregulating the energetic maintenance protein HDHD3. Furthermore, chemical-protein interactions revealed that HDHD3 was linked to the energy homeostatic pathway. Conclusion: CO may benefit liver function by preserving hepatic mitochondrial architecture and increasing energy metabolic activity.

The effects of astaxanthin on liver histopathology and expression of superoxide dismutase in rat aflatoxicosis.

The metabolism of aflatoxin B1 (AFB1) generates reactive oxygen species (ROS) that destroys hepatocytes. Meanwhile, astaxanthin (AX) is known to have stronger antioxidative activity than other carotenoids. This study aimed to investigate hepatoprotective role of AX from AFB1-induced toxicity in rat by histopathological study and immunohistochemistry of Cu/Zn-SOD (SOD1) which acts as the first enzyme in antioxidative reaction against cell injury from ROS. Twenty Wistar rats were randomly divided into 4 groups. The control and AFB1 groups were gavaged by water for 7 days followed by a single DMSO and 1 mg/kg AFB1, respectively. The AXL+ AFB1 and AXH+ AFB1 groups were given of 5 mg/kg and 100 mg/kg AX for 7 days before 1 mg/kg AFB1 administration. The result showed significantly elevated liver weight per 100 g body weight in AFB1 group. The histopathological finding revealed vacuolar degeneration, necrosis, megalocytosis and binucleation of hepatocytes with bile duct hyperplasia in AFB1 group. The severities of pathological changes were sequentially reduced in AXL+AFB1 and AXH+AFB1 groups. Most rats in AXH+AFB1 group owned hypertrophic hepatocytes and atypical proliferation of cholangiocytes which are adaptive responses to severe hepatocyte damage. The SOD1 expression was also significantly higher in AXH+AFB1 group than solely treated AFB1 and AXL+AFB1 groups. In conclusion, AX alleviated AFB1-induced liver damage in rat by stimulating SOD1 expression and transdifferentiation of cholangiocytes in dose dependent manner.

Reproductive toxicity of Momordica charantia ethanol seed extracts in male rats.

BACKGROUND: Momordica charantia (M. charantia) seed has been supposed to have an antifertility property but mechanisms underlying the infertility effect have not been investigated. OBJECTIVE: We investigated the antifertility effect of M. charantia ethanol seed extracts on reproductive toxicology and seminal and plasma testosterone in male Wistar rats. MATERIALS AND METHODS: The control group (I) was provided daily 1 ml dimethylsulfoxide (DMSO) and the experimental groups II and III were given daily 400 and 800 mg dry matter/kg body weight of the extracts dissolved in 1 ml DMSO via the esophageal route. All groups were administered for 42 days (day 42). Changes in body weight, fertility, reproductive characteristics, testicular histopathology and levels of seminal and plasma testosterone among three groups were compared. RESULTS: On day 42, the extracts caused antifertility (p=0.001). The extracts demonstrated significant reductions in diameters of seminiferous tubules and epididymides, spermatid density, daily sperm production and caudal epididymal spermatozoa, sperm motility and viability (p=0.046). Pathological changes in seminiferous tubules revealed atrophy, desquamation, pyknosis nucleus and multinucleated giant cell. Plasma cells were evident in three parts of epididymides of rats treated with high dose of the extract. Furthermore, the high dose of the extract suppressed seminal testosterone level (p=0.001) and plasma testosterone level (p=0.002). CONCLUSION: Our data showed that high dose of M. Charantia seed extracts caused infertility in male rats. The interruption in their fertility was probably attributed to the direct toxic to seminiferous tubules, epididymis and the lowered testosterone level which might impact on sperm parameters.

Focal adhesion kinase and Src phosphorylations in HGF-induced proliferation and invasion of human cholangiocarcinoma cell line, HuCCA-1.

AIM: To study the role of focal adhesion kinase (FAK) and its association with Src in hepatocyte growth factor (HGF)-induced cell signaling in cholangiocarcinoma progression. METHODS: Previously isolated HuCCA-1 cells were re-characterized by immunofluorescent staining and reverse transcriptase-polymerase chain reaction assay for the expression of cytokeratin 19, HGF and c-Met mRNA. Cultured HuCCA-1 cells were treated with HGF and determined for cell proliferation and invasion effects by MTT and invasion assays. Western blotting, immunoprecipitation, and co-immunoprecipitation were also performed to study the phosphorylation and interaction of FAK and Src. A novel Src inhibitor (AZM555130) was applied in cultures to investigate the effects on FAK phosphorylation inhibition and on cell proliferation and invasion. RESULTS: HGF enhanced HuCCA-1 cell proliferation and invasion by mediating FAK and Src phosphorylations. FAK-Src interaction occurred in a time-dependent manner that Src was proved to be an upstream signaling molecule to FAK. The inhibitor to Src decreased FAK phosphorylation level in correlation with the reduction of cell proliferation and invasion. CONCLUSION: FAK plays a significant role in signaling pathway of HGF-responsive cell line derived from cholangiocarcinoma. Autophosphorylated Src, induced by HGF, mediates Src kinase activation, which subsequently phosphorylates its substrate, FAK, and signals to cell proliferation and invasion.