Zuotai (gTso thal) is a typical representative of Tibetan medicines containing heavy metals, but there is still lack of modem safety evaluation data so far. In this study, acute toxicity test, sub-acute toxicity test, one-time administration mercury distribution experiment, long-term mercury accumulative toxicity experiment and preliminary study on clinical safety of Compound Dangzuo were conducted in the hope of obtain the medicinal safety data of Zuotai. In the acute toxicity test, half of KM mice given the lethal dose of Zuotai were not died or poisoned, and LD50 was not found. The maximum tolerated dose of Zuotai was 80 g x kg(-1). In the subacute toxicity test, Zuotai could reduce ALT, AST, Crea levels in serums under low dose (13.34 mg x kg(-1) x d(-1)) and medium dose (53.36 mg x kg(-1) x d(-1)), with significant difference under low dose, and increase the levels of ALT, AST, MDA, Crea in serums under high dose (2 000 mg x kg(-1) x d(-1)); besides, the levels of BUN and GSH in serums reduced with the increase in dose of Zuotai, indicating a significant dose-effect relationship. In the one-time administration distribution experiment, the content of mercury in rat kidney, liver and lung increased after the one-time administration with Zuotai, with a significant dose-dependent relationship in kidney. In the long-term mercury accumulative toxicity experiment, KM mice were administered with equivalent doses of Zuotai for 4.5 months and then stopped drug administration for 1.5 months. Since the 2.5th month, they showed significant mercury accumulation in kidney, which gradually reduced after drug withdrawal, without significant change in mercury content in liver, spleen and brain and ALT, AST, TBIL, BUN and Crea in serum. At the 4.5th month after drug administration, KM mice showed slight structural changes in kidney, liver and spleen tissues, and gradually recovered to normal after drug withdrawal. Besides, no significant difference in weight gain was found between the Zuotai group and the control group. According to the findings of the clinical safety study of Dangzuo, after subjects administered Dangzuo under clinical dose for one month, their serum biochemical indicators, blood routine indicators and urine routine indicators showed no significant adverse change. This study proved that traditional Tibetan medicine Zuotai was slightly toxic, with a better safety in clinical combined administration and no adverse effects on bodies under the clinical dose and clinical medication cycle. However, long-term high-dose administration of Zuotai may have a certain effect on kidney.
Adult ; Animals ; Clinical Trials as Topic ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; toxicity ; Female ; Humans ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Medicine, Tibetan Traditional ; Mice ; Middle Aged ; Rats ; Rats, Wistar ; Young Adult

Sensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca

Aim To study the effect of different hepa- ry.Methods First, heparin derivatives with different rin sulfation patterns on bleomycin induced lung inju- sulfation patterns,6-desulfated heparin (6-DeH) and N-acetvlated heparin ( N-AcH ) , were synthesized.Secondly, the effect of these compounds on BLM-in¬duced bronchial epithelial cell ( BEARS-2B) injury was evaluated via lactate dehydrogenase activity, MTT experiment, Annexin V/ PI staining and Hoechst 33258 staining.Then , immunofluorescence staining and West¬ern blotting were used to investigate the shedding of Svndecan-1 and the activation of c-Met by 6-DeH/Akt j j signaling pathway.Finally, a BLM-induced lung injury mouse model was used to further verify the protective effect of 6-DeH by HE staining, Svndecan-1 immunos- taining,bodv weight change,and survival rate.Results In the BLM-induced BEARS-2B injury model, 6- DeH was selected as the best candidate, which exerted their effect by competitively binding to BLM, thereby reducing the damage of heparan sulfate barrier (Svnde- can-1 ) on cell surface, and improving cell survival by activating the downstream c-Met/Akt pathway.In the BLM-induced lung injury mouse model, it was further confirmed that 6-DeH reduced the shedding of Svnde- can-1 in the early stage, and delayed the lung injury and fibrosis process.Conclusions 6-DeH protects the bronchial epithelial cells against BLM-induced lung in¬jur)' through inhibiting the shedding of Svndecan-1 and activating the c-Met/Akt signaling pathway.