Protective effect of microorganism biotransformation-produced resveratrol on the high fat diet-induced hyperlipidemia, hepatic steatosis and synaptic impairment in hamsters.

Background: Resveratrol, a natural antioxidant polyphenol, has the functions of anti-inflammation, anti-cancer, liver protection and cardioprotection. Microorganism biotransformation-produced resveratrol (MBR) product shows higher purity than the natural source of resveratrol and costs less than the chemically synthesized resveratrol. The aim of the present study was to investigate the protective effects of MBR in hamsters treated with a high-fat diet (HFD). Methods: MBR was obtained by the fermentative process of piceid. Hamsters were randomly divided into four groups: HFD plus oral administration of MBR 0 (C), 5 (L), 20 (M) or 50 mg/kg (H), respectively. After six-week of treatment, hamsters were sacrificed, and tissues were collected for further analysis. Results: MBR at these three dosages did not influence the appetite or growth of the hamsters. Liver enzymes, blood glucose, total cholesterol, triglyceride, and liver weight were significantly reduced in the MBR groups than in the control group. Additionally, high-density lipoprotein-cholesterol (HDL-C) was also elevated in all MBR groups. On the other hand, serum low-density lipoprotein-cholesterol (LDL-C) was decreased in the MBR groups. Triglyceride (TG) in liver tissue and fatty liver level were lower in group H. Memory-associated proteins, phosphorylation of calmodulin-dependent protein kinase II (p-CaMK II) and synaptophysin (SYP), were increased in the brains of MBR groups. Conclusion: The high yield- and short procedure-produced MBR has the potential to protect animals fed with HFD from hyperlipidemia, hepatic steatosis, hyperglycemia, and synaptic impairment, which might be beneficial for patients with these types of diseases.

Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies.

In a previous study, treatment at higher concentrations of arsenic trioxide or co-exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis-related protein (MMP-2, MMP-9, and VEGF-A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co-exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound-healing activities, migration abilities, and MMP-2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug-treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP-2, MMP-9, and VEGF-A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121-1132, 2016.

The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae).

The in vivo antioxidant and antifibrotic properties of green tea (Camellia sinensis, Theaceae) were investigated with a study of carbon tetrachloride (CCl(4))-induced oxidative stress and hepatic fibrosis in male ICR mice. Oral administration of green tea extract at doses of 125, 625 and 1250 mg/kg for 8 weeks significantly reduced (p<0.05) the levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyls in the liver by at least 28% compared with that was induced by CCl(4) (1 mL/kg) in mice. Moreover, green tea extract administration significantly increased (p<0.05) the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver. Our study found that oral administration of green tea extract prevented CCl(4)-induced hepatic fibrosis, as evidenced by a decreased hydroxyproline level in the liver and a reduced incidence of hepatic fibrosis by histological observations. These results indicate that green tea exhibits potent protective effects against CCl(4)-induced oxidative stress and hepatic fibrosis in mice by inhibiting oxidative damage and increasing antioxidant enzyme activities.

Humic acid enhances the cytotoxic effects of arsenic trioxide on human cervical cancer cells.

Cervical cancer is the second leading cancer affecting women, and recent studies have demonstrated arsenic trioxide (As(2)O(3)) has therapeutic effects on cervical cancer by promoting apoptosis and inhibiting metastasis in vitro and in vivo. Humic acid (HA) possesses various pharmacologic properties, including anti-inflammatory, anti-neoplastic, and anti-proliferative effects by inducing apoptosis. We examined the growth inhibition properties and the combined effects of HA and As(2)O(3) in human cervical adenocarcinoma cell lines. Our results shown both As(2)O(3) and HA-induced inhibition of cell growth, most likely by ROS-mediated cell damage and activation of the apoptosis pathway, and HA enhanced the anti-proliferative action of As(2)O(3) in HeLa and SiHa cells, which reduced the LC(50) about 57.62 or 73.52% (300µg HA/mL) to 83.67 or 79.03% (500µg HA/mL), respectively. This study is relevant to the development of chemotherapeutic approaches using As(2)O(3) in treating human cervical cancer.

45,X/46,XX mosaicism in a mother and one of her discordant monozygotic twin daughters: report of one case.

Decreased fertility is one of the characteristics of Turner syndrome. Ovarian function in women with Turner syndrome is believed to be impaired because of an abnormal and very rapid maturation of oocytes and follicles. About 30% of mosaic Turner patients have partial ovarian function during puberty, but only 2-5% of them will ever become pregnant. We describe a woman with a mosaic form of Turner syndrome (45,X [6]/146,XX [94] karyotype from blood lymphocytes), who had a spontaneous puberty and normal fertility. After her second pregnancy, she gave birth to a set of monozygotic female twins; Twin B presented with a mild Turner syndrome phenotype and Twin A with a normal female phenotype. Karyotypic analysis performed on amniotic fluid and fetal blood samples demonstrated a normal 46,XX chromosome constitution in Twin A and a 45,X/46,XX mosaicism (27%:73% for amniotic fluid and 6%:94% for fetal blood) in Twin B. Postnatal cytogenetic investigation of blood lymphocytes showed the 45,X [7]/46,XX [93] mosaicism in Twin B. Further investigations of blood lymphocytes in both girls at the age of 4 years showed Twin A with a 46,XX karyotype and Twin B with a 45,X [4]/46,XX [96] mosaicism. The phenotype of twin A had a normal appearance, but webbing of the neck, low posterior hair line, shield chest, and mild psychomotor retardation were evident in Twin B.