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In recent years, herbal tea consumption becomes popular because of the potential health benefits and attractive flavors. However, there is also a growing concern that herbal supplements contribute to the drug-drug/drug-herb interactions and hepatotoxicity. In this study, FL83B mouse hepatocytes were used as an in vitro mode of hepatotoxicity induced by free fatty acids, including palmitic acid (PA) and oleic acid (OA), ethanol, and acetaminophen. Herbal tea extracts were obtained from eight common herbal plants, including Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., Citrus maxima (Burm.) Merr., Citrus limon (L.) Osbeck, and Ficus formosana Maxim. MTT assay was used to evaluate the impact of these herbal tea extracts on hepatoxocitity. We found that these herbal tea extracts per se did not exhibit hepatotoxicity, and had no effect on OA-induced hepatotoxicity. However, extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., and Hemerocallis fulva (L.) L. exhibited protective effect against PA-induced hepatotoxicity. In addition, herbal tea extracts from Verbena officinalis L., Hyssopus officinalis L., Salvia officinalis L., Urtica dioica L., Hemerocallis fulva (L.) L., and Ficus formosana Maxim. exhibited protective effect against acetaminophen-induced hepatotoxicity. Interestingly, all these herbal tea extracts enhanced ethanol-induced hepatotoxicity. Our results suggest that herbal tea extracts have differential effects on different modes of hepatotoxicity. [ABSTRACT FROM AUTHOR]

The use of additives in different food products is growing up. It has attracted the attention towards the relation between the mutagenic potential of human diseases and food additives. Sunset yellow (SY) and sodium benzoate (NaB) are used as colorant and food additives worldwide. In the present study, genotoxic effects of different combinations of SY and NaB were assessed in vivo in female rats. Different combinations of SY and NaB were dissolved in water and administered daily to six animals groups for 12 weeks. Group 1 (control) received water, Group 2 received 5 mg/kg body weight (bw) SY plus 10 mg/kg bw NaB, group 3 received 5 mg/kg SY plus 100 mg/kg NaB, group 4 received 50 mg SY plus 100 mg/kg NaB, group 5 received 50 mg/kg SY plus 10 mg/kg NaB, group 6 received 200 mg/kg SY plus 750 mg/kg NaB, and group 7 received 20 mg/kg SY plus 75 mg/kg NaB. Genotoxicity investigations (Chromosomal aberration of bone marrow cells, Comet assay and DNA profile of liver cells) were carried out at the end of the experiment. Administration of 200 mg/kg SY plus 750 mg/kg NaB (group 6) induced the highest abnormalities percentage (1.5%) and showed structural abnormalities including end-to-end association, fragmentation, chromatid break, ring chromosome, and centric fusion break of chromosomes. Different combinations of SY and NaB induced an increase in the frequency of tailed nuclei (DNA damage) in liver cells. A concentration-dependent distinct DNA smear pattern was observed in the DNA isolated from liver cells of animals administered SY and NaB. In addition, administration of SY plus NaB resulted in an abnormal distribution of serum proteins. The results showed that the SY plus NaB could have genotoxic potential. With the increase applications of food additives, this study reported important data about screening the potential impacts. [ABSTRACT FROM AUTHOR]

Citral, 3,7-dimethyl-2,6-octadien-1-al, one of the main components of the essential oils obtained from several plants, is used as a food additive and as a fragrance for detergents, cosmetics and other toiletries. The literature shows disparity regarding citral genotoxicity. Thus, the main objective of our work was to evaluate the genotoxic effects of citral in human cell cultures, HepG2 and leukocytes. Cytotoxicity assays (trypan blue and MTT) showed citral toxic effects in HepG2 cells (with metabolizing liver enzymes), which contrasted with the absence of toxicity in leukocytes. After citral exposure, both cell types did not demonstrate clastogenic/aneugenic effects in the micronucleus test. However, for the comet assay, citral exposure lead to significant genotoxic effects in both HepG2 (even to citral low concentrations) and leukocytes. The use of citral must be viewed with caution due to its ability to induce DNA damages, especially after being metabolized by cells with active liver enzymes. [ABSTRACT FROM AUTHOR]

Apart from using traditionally in culinary preparations, chili peppers are also important constituents of herbal medicines. Although the bioactive components are studied mostly in the fruits of Capsicum annuum, no such study reports till date is available for Ghost chili (C. chinense) from North East India. Therefore, the aim of this study was to carry out an analysis of the bioactive constituents in the naturally occurring hottest chili Ghost chili (C. chinense), and evaluate its antioxidant, pro/anti-genotoxic, and apoptotic effects in in vitro and in vivo models. Three different antioxidant assays showed that lower doses of Ghost chili extract showed higher DNA protective and antioxidant activities. Furthermore, the administration for 7 alternate days into 6 week old Swiss albino mice showed that the lower doses (50 and 100 mg/kg bw) reduced DMBA induced genotoxicity beside significantly enhancing the activities of hepatic antioxidant enzymes, while higher dose (200 mg/kg bw) induced genotoxic effect in bone marrow cells. The administration of higher dose (200 mg/kg bw) also induced apoptosis and upregulation of Bax (pro) and downregulation of Bcl-2 (anti) apoptotic genes. Dose dependent increase of apoptosis was also observed in Hep G2 and Hep 3B liver cancer cell lines. Our findings in the present study suggest that low doses of C. chinense can exert cancer chemopreventive effects. The induction of apoptosis in both cancer cell lines and mouse bone marrow cells, and up-regulation of proapoptotic genes suggests that the higher dose of C. chinense can be used for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Due to their beneficial health effects, strawberry tree (Arbutus unedo L.) leaves have for decades been used as herbal remedy in countries of the Mediterranean region. This pilot study is the first to investigate the liver function and DNA integrity in rat hepatocytes evaluated after 14 and 28 day treatments with strawberry tree water leaf extract and arbutin, administered per os to Lewis rats of both genders at a daily dose 200 mg/kg b.w. We focused on two types of biomarkers: enzyme serum markers of liver function (AST, ALT, and LDH), and primary DNA damage in the liver cells, which was estimated using the alkaline comet assay. At the tested dose, strawberry tree water leaf extract showed acceptable biocompatibility with liver tissue both in male and female rats, especially after shorter exposure. Our results also suggest that oral administration of single arbutin to rats was not associated with significant impairments either in the liver function or DNA integrity in hepatocytes. Considering that prolonged exposure to the tested compounds revealed minor changes in the studied biomarkers, future in vivo studies have to further clarify the biological and physiological relevance of these findings. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants in aquatic ecosystems, which may have potentially toxic effects on organisms. In this study occurrence of DNA strand breaks, oxidative stress, and cytotoxicity were investigated in rainbow trout hepatocytes following in vitro exposure for 24 h to four PAHs (0.01–10 µM): naphthalene, fluoranthene, pyrene, and benzo[a]pyrene (B[a]P). The exposed hepatocytes were analyzed for DNA strand breaks using the comet assay and for antioxidant status by measuring intracellular glutathione (GSH) content using the fluorescent probe mBCl. The cytotoxicity of PAHs was assessed using the fluorescent probe CFDA-AM. The results showed that fluoranthene, pyrene, and B[a]P were genotoxic at all exposure concentrations, whereas naphthalene was genotoxic at concentrations ≥0.1 µM. All treatments reduced the intracellular concentrations of GSH for all four PAHs, except 10 µM of B[a]P, suggesting that some level of oxidative stress was present. The cytotoxic effect was observed for naphthalene at concentrations ≥0.1 µM and pyrene at all exposure concentrations, whereas fluoranthene and B[a]P were not cytotoxic at the tested concentrations. The study shows that low-molecular-weight PAHs may cause DNA strand breaks as high-molecular-weight PAHs do in fish tissue. In addition, two- to five-ring PAHs can induce oxidative stress and cytotoxicity. [ABSTRACT FROM AUTHOR]

Bisphenol F (BPF) is present in the environment and as a contaminant of food. Humans may, therefore, be exposed to BPF, and an assessment of this risk is required. BPF has been shown to have genotoxic and endocrine-disruptor properties in a human hepatoma cell line (HepG2), which is a model system for studies of xenobiotic toxicity. In this study, we investigated the ability of HepG2 cells to biotransform BPF, because metabolism may affect the observed effects of BPF, and we compared this metabolic capacity with that of human hepatocytes. Cells were incubated for 24 hours with [3H]-BPF. The culture medium was then concentrated and its metabolites were isolated by high-performance liquid chromatography and identified by mass spectrometry. BPF was largely metabolized into the corresponding sulfate by the HepG2 cell line. BPF was metabolized into both sulfate and glucuronide by human hepatocytes, but with differences between individuals. The metabolism of BPF in both HepG2 cells and human hepatocytes suggests the existence of a detoxification pathway. Thus, these two cell models differ in metabolic capacity. It is, therefore, very important, when assessing the toxic effects of substances in vitro, to determine, in parallel, the biotransformation capacities of the model used to extrapolate in vivo. [ABSTRACT FROM AUTHOR]

Penitrem A is a potent neurotoxin produced by several species in the genus Penicillium, which primarily affects the central nervous system. The toxin has several effects on neurotransmitter release, both at the central and peripheral level, as well as on ion channels. We have evaluated the hepatic metabolism of penitrem A by rat hepatocytes and rat-liver microsomes in vitro. In addition, we have conducted an in vivo study in mice and determined metabolites in several organs. According to our results, penitrem A is extensively metabolized in the liver to at least five metabolites more hydrophilic than the parent compound. [ABSTRACT FROM AUTHOR]

Fumonisin B1 (FB1), the most prevalent member of toxins produced by several species of Fusarium molds, which occur mainly in maize, causes several fatal hepatopathies and nephropathies of animals. The current study was scrutinized to ascertain different cytotoxic and morphological transformations in rat hepatocytes induced by the treatments of diverse concentrations (300, 500, or 1000 μM) of fumonisin B1 in vitro, using both monolayer and spheroid cultures. In each hepatocyte culture, the cytotoxicity of FB1 was augmented in dose- and time-response manners. Morphological transformations among FB1-treated groups integrated accumulation of lipid droplets, cytoplasmic vacuolation in hepatocyte monolayers, and bleb formation in the hepatocyte spheroids. Additionally, electron microscopy revealed the loss of microvilli, mitochondrial swelling, and formation of lamellar membranous whorl in the vacuoles and bile canaliculi-like structures. Appearance of electron dense bodies in the monolayers, and loss of cell-to-cell contact in spheroids were depicted in 1000 μM FB1-treated hepatocytes. These outcomes insinuate different vital events in explaining morphological transformations in the cell membrane and organelles, induced by fumonisins in rat hepatocytes. [ABSTRACT FROM AUTHOR]

Our aim was to study the distribution of dolichol, dolichol isoprenoids, and retinol in hepatocytes, Kupffer, sinusoidal endothelial and two subfractions of hepatic stellate cells, —Ito-1 and Ito-2—, after chronic treatment of rats for 2 and 4 months with a low dosage of thioacetamide associated with ethanol. Each type of cell responded differently to the two hepatotoxins. Overall, ethanol rarely affected the action of thioacetamide. Some new information emerges with regard to these hepatotoxins in comparison with the effects exerted by each of the drugs separately: treatment with thioacetamide plus ethanol determined an early decrease in dolichol in Kupffer cells (about 13% and 50% after 2 and 4 months, respectively). Moreover, after liver damage, a load of vitamin A evidenced altered percentages of the form of dolichol with eighteen isoprene units; these percentages were modified by all treatments in all cell types. The results confirm that dolichol is the preferred target of oxidative stress and suggest a relationship between dolichol and retinol metabolisms, and a possible new role of dolichol precursors, of prenyltransferases and of retinol metabolites in liver pathology. [ABSTRACT FROM AUTHOR]