Objective To study the chronic toxicity and its severity of a Chinese medicine, Anshen Bunao Liquid ( ABL) , in rats, provide the target organs and extent of reversibility of their adverse effects, determine its non-toxic dose, and to evaluate the safety of medication and provide reference for clinical trial dose and observation indexes.Methods Two hundred and forty healthy 6-week old Wistar rats ( male:female=1:1) were divided into low,middle, and high dose Anshen Bunao liquid groups (2.5, 5, 10 mL/kg),and solvent control group (distilled water 2 mL/100 g), with 60 rats in each group.The drug was orally administered to rats once a day and 6 days per week for 26 weeks.The general state, body mass and food intake were measured.By the end of 13 weeks, 26 weeks of experiment and 4-week recovery period after drug withdrawal, hematological and biochemical indexes were assayed, organ coefficients were determined, and histopathological observation was performed.Results Long-term continuous oral administration of Anshen Bunao liquid, the general state, behavior and gross appearance showed no significant abnormal changes.Compared with the control group, no significant differences in all checked items were found in the treatment groups.During 3 and 6 months, the size and location of organs,organ weight and organ coefficient had no obvious changes, with only non-significant increase of weight of some organs.All the organ coefficients of the animals in different groups were within normal range.Histopathology showed no obvious patho-logical and toxicological changes even in the high-dose drug treatment group, and no delayed toxicity occurred after with-drawal of drug administration.Conclusions The Chinese drug, Anshen Bunao liquid has no obvious toxicity and no de-layed toxicity after withdrawal of the drug in rats.It is expected that the planned dose in clinical use is a safe dose.

OBJECTIVEThrough the paired comparison on the toxicity effect of Aconiti Lateralis Radix Praeparata of different compatibility proportion of Aconiti Lateralis Radix Praeparata and Glycyrrhizae Radix et Rhizoma, to observe the detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata.

METHODPaired comparison on the mouse acute toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the LD50. Paired comparison on the rat heart toxicity of Aconiti Lateralis Radix Praeparata and Aconiti Lateralis Radix Praeparata with different compatibility proportion of Glycyrrhizae Radix et Rhizoma, to assay the TD50. We dilute medicated serum of Aconiti Lateralis Radix Praeparata, Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (3:1), Aconiti Lateralis Radix Praeparata plus Glycyrrhizae Radix et Rhizoma (1: 1) into 5%, 10%, 20% solution with serum free DMEM, to survey the effect of different concentration of medicated serum to the pulsing rhythm of myocardial cell of original generation newborn rat, cell surviva rate and content of LDH in myocardial cells.

RESULTLD50 and TD50 of Aconiti Lateralis Radix Praeparata can be increased after adding Glycyrrhizae Radix et Rhizoma Compared to the blank serum, medicated serum with Aconiti Lateralis Radix Praeparata can obviously increased the pulse rhythm of myocardial cell and the content of LDH (P < 0.05). The medicated serum with Aconiti Lateralis Radix Praeparata added different proportion of Glycyrrhizae Radix et Rhizoma can reduce the acceleration of myocardial cell's rhythm, which is induced by Aconiti Lateralis Radix Praeparata, and can reduce the content of LDH. With the increased ratio of Glycyrrhizae Radix et Rhizoma, the effect is stronger. But for the serum with different concerntration of Aconiti Lateralis Radix Praeparata or Aconiti Lateralis Radix Praeparata added Glycyrrhizae Radix et Rhizoma, there is no obvious effect to the cell survival.

CONCLUSIONGlycyrrhizae Radix et Rhizoma has the detoxication effect through increasing the ultimatetotaldosage of Aconiti Lateralis Radix Praeparata. The detoxication effect of Glycyrrhizae Radix et Rhizoma to Aconiti Lateralis Radix Praeparata is through restraining the increased rhythm of myocardial cell and protecting the myocardial cell.

Aconitum ; chemistry ; Animals ; Cells, Cultured ; Chemistry, Pharmaceutical ; methods ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; toxicity ; Female ; Glycyrrhiza ; chemistry ; Inactivation, Metabolic ; Male ; Mice ; Mice, Inbred ICR ; Myocytes, Cardiac ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhizome ; chemistry

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.