Scutellaria Root extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Scuellaria Root (SR, root of Scutellaria baicalensis), which has potent anti-inflammatory effects, is a component of useful Kampo formulae. Albeit a low frequency, SR induces serious interstitial pneumonia and liver dysfunction. In this study, to control the adverse effects of SR, we investigated the causal constituent responsible for its hepatocytotoxicity and aimed to develop a method to control it. As a result, we revealed that the hepatocytotoxicity of SR was correlated with its baicalin content, a major constituent in SR. It was confirmed by preparing a baicalin-free SR extract, which exhibited reduced hepatocytotoxicity. The addition of baicalin to the baicalin-free SR extract restored the hepatocytotoxicity, indicating that the hepatocytotoxicity of SR is dependent on its baicalin content. Thus, SR extract-induced hepatocytotoxicity can be controlled by regulating its baicalin content.

Structural Characterization of Polysaccharides from Coriandrum sativum Seeds: Hepatoprotective Effect against Cadmium Toxicity In Vivo.

Coriandrum sativum is one of the most widespread curative plants in the world, being vastly cultivated in arid and semi-arid regions as one of the oldest spice plants. The present study explored the extraction of polysaccharides from Coriandrum sativum seeds and the evaluation of their antioxidant potential and hepatoprotective effects in vivo. The polysaccharide from coriander seeds was extracted, and the structural characterization was performed by FT-IR, UV-vis, DSC, NMR (1D and 2D), GC-MS, and SEC analysis. The polysaccharide extracted from Coriandrum sativum (CPS) seeds was characterized to evaluate its antioxidant and hepatoprotective capacities in rats. Results showed that CPS was composed of arabinose, rhamnose, xylose, mannose, fructose, galactose, and glucose in molar percentages of 6.2%, 3.6%, 8.8%, 17.7%, 5.2%, 32.9%, and 25.6%, respectively. Further, CPS significantly hindered cadmium-induced oxidation damage and exercised a protective effect against Cd hepatocytotoxicity, with a considerable reduction in MDA production and interesting CAT and SOD enzyme levels. Results suggest that CPS might be employed as a natural antioxidant source.

Is it really safe to replace decabromodiphenyl ether (BDE209) with decabromodiphenyl ethane (DBDPE)?: A perspective from hepatotoxicity.

In this paper, the hepatocytotoxicity and aryl hydrocarbon receptor (AHR) activity of decabromodiphenyl ethane (DBDPE), decabromodiphenyl ether (BDE209) and other 18 analogues were evaluated in vitro using human normal liver cell L02. These dioxin-like compounds showed differential hepatocytotoxicity (EC50  = 0.38-17.87 mg/L) and AHR activity (EROD activity = 4.53-46.35 U/µg). In silico study indicated the distance of π-π bonds between the benzene ring of compounds and residue Phe234 of AHR played a key role in the binding of AHR, and the substituents on the benzene ring also influenced the activity. Combining molecular biology and bioomics, the comprehensive investigations on the hepatotoxic mechanisms have demonstrated the AHR signaling pathway was the key mediation mechanism for the hepatotoxicity of DBDPE/BDE209. The cytochrome P450s (CYP2 family) mediated formation of reactive oxygenated intermediates might be the dominant toxic mechanism, which could produce oxidative stress or cause genotoxicity. Although the experimental toxicity of DBDPE was smaller relative to BDE209, the health risk of DBDPE may be much greater than we expected, due to the high potential to form a variety of dioxin-like intermediates by microbial oxidation of ethyl group. Therefore, whether it is really safe to replace BDE209 with DBDPE is a debatable question, and more ecotoxicological and health data are needed to clarify this issue.

Alcoholic-Hepatitis, Links to Brain and Microbiome: Mechanisms, Clinical and Experimental Research.

The following review article presents clinical and experimental features of alcohol-induced liver disease (ALD). Basic aspects of alcohol metabolism leading to the development of liver hepatotoxicity are discussed. ALD includes fatty liver, acute alcoholic hepatitis with or without liver failure, alcoholic steatohepatitis (ASH) leading to fibrosis and cirrhosis, and hepatocellular cancer (HCC). ALD is fully attributable to alcohol consumption. However, only 10-20% of heavy drinkers (persons consuming more than 40 g of ethanol/day) develop clinical ALD. Moreover, there is a link between behaviour and environmental factors that determine the amount of alcohol misuse and their liver disease. The range of clinical presentation varies from reversible alcoholic hepatic steatosis to cirrhosis, hepatic failure, and hepatocellular carcinoma. We aimed to (1) describe the clinico-pathology of ALD, (2) examine the role of immune responses in the development of alcoholic hepatitis (ASH), (3) propose diagnostic markers of ASH, (4) analyze the experimental models of ALD, (5) study the role of alcohol in changing the microbiota, and (6) articulate how findings in the liver and/or intestine influence the brain (and/or vice versa) on ASH; (7) identify pathways in alcohol-induced organ damage and (8) to target new innovative experimental concepts modeling the experimental approaches. The present review includes evidence recognizing the key toxic role of alcohol in ALD severity. Cytochrome p450 CYP2E1 activation may change the severity of ASH. The microbiota is a key element in immune responses, being an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. Alcohol consumption changes the intestinal microbiota and influences liver steatosis and liver inflammation. Knowing how to exploit the microbiome to modulate the immune system might lead to a new form of personalized medicine in ALF and ASH.

Bioactive luteoloside produced by Myroides odoratimimus, solvent-tolerant bacterium form the rhizosphere of Lonicera japonica.

Luteoloside (luteolin-7-O-glucoside), the biomarker of Lonicera japonica, was efficiently bio-synthetized from its cheaper precursor luteolin. The structure of luteoloside was characterized by LC-MS and NMR analyses. Compared to the significant inhibitory effect of luteolin on human hepatocyte cell line LO2 at high doses, luteoloside did not show obvious cytotoxic effects at any test dose. Moreover, luteoloside exhibited obvious promotive effects on human hepatocyte cells, suggesting a potential application in hepatoprotective therapies.

Adverse drug reactions induced by valproic acid.

Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity.