Advances in mechanism of methotrexate on toxicity in various organs / 中国药理学通报

As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.

Study on effects of dioscin against depression and its mechanisms / 中国药理学通报

Aim To investigate the effects and possible molecular mechanisms of dioscin(DIO)against depression in mice.Methods Eighty mice were randomly divided into control group, DIO control group, model group, DIO groups(20, 40 and 80 mg·kg-1 DIO)and FLU group(20 mg·kg-1 fluoxetine).After establishing the depression model with chronic unpredictable moderate stress(CUMS)in mice, the corresponding drugs were administered by gavage continuously for four weeks in each group.The behavior of mice was tested, and the contents of corticosterone(CORT), brain-derived neurotrophic factor(BDNF), 5-hydroxytryptamine(5-HT), malondialdehyde(MDA), superoxide dismutase(SOD)and catalase(CAT)were evaluated by ELISA or enzyme labeling method.In addition, HE staining, Nissl staining and PET scanning were operated for the brain tissues.Western blot was used to detect the protein expressions.Results Compared with model group, DIO significantly improved the behaviors of depressed mice.And it reduced the contents of CORT in serum, increased BDNF and 5-HT in hippocampus.Meanwhile, DIO obviously reduced MDA in serum, increased SOD in serum and CAT in brain tissues.DIO improved the steatosis of brain tissues, disorder and looseness of neurons, and increased glucose metabolism in brain tissues of depressed mice.The molecular mechanism suggested that compared with model group, DIO significantly increased the protein level of UCP2 to adjust the levels of Nrf2, SOD2, GLUT1 and G6Pase.Conclusions DIO improves the depression symptoms of depressed mice, which should be through adjusting UCP2-mediated oxidative stress and glucose metabolism.

Molecular mechanism of cisplatin-induced nephrotoxicity and intervention of traditional Chinese medicine / 中国药理学通报

Cisplatin (DDP) is one of the most commonly used medicines in combination chemotherapy; however, its clinical upplicaiion is greatly limited by nephrotoxicity. In the present paper, the molccular mechanisms including cytotoxicity, oxidative stress, inflammation and apoptosis signaling pathways on DDP-induccd nephrotoxicity were discussed, and the relationship between DDP-induced nephrotoxicity and transporters and raiRNAs was also analyzed. In addilion, recent advances on tra-ditional Chinese medicines (TCMs) for the preventicn and treatment of DDP-induced nephrotoxicity were reviewed, aiming to provide useful information for the research and development of innovative drugs in the treatment of DDP-induced nephrotoxicity. Key words: Cisplatin; nephrotoxicity; cytotoxicity; oxidative stress; inflammation; apoplosis; traditional Chinese medicine.