The protective effect of L-glutamine against acute Cantharidin-induced Cardiotoxicity in the mice.

BACKGROUND: Cantharidin (CTD) is a compound which have the potential to be exploited as an antitumor drug, and it has been demonstrated antitumor effects in a variety of cancers. However, the use is limited due to its severe toxicity. It has reported that it can induce fatal cardiac arrhythmias. Fortunately, we found that L-glutamine can alleviate cardiac toxicity caused by cantharidin in mice. METHODS: To investigate the protective effect of L-glutamine, we used a high dose of cantharidin in mice to create a model of cardiotoxicity. In the experimental mice, glutamine was given orally half an hour before they were administrated with cantharidin. The mice of control group were intraperitoneally injected with DMSO solution. The general state of all mice, cardiac mass index, electrocardiogram change and biological markers were determined. Hematoxylin-eosin staining (HE staining) of heart tissue was carried out in each group to reflect the protective effect of glutamine. To investigate the mechanisms underlying the injury and cardio-protection, multiple oxidative stress indexes were determined and succinate dehydrogenase activity was evaluated. RESULT: The results showed that L-glutamine (Gln) pretreatment reduced weight loss and mortality. It also decreased the biological markers (p < 0.05), improved electrocardiogram and histological changes that CTD induced cardiotoxicity in mice. Subsequently, the group pretreated with L-glutamine before CTD treatment increases in MDA but decreases in SOD and GSH, in comparison to the group treated with CTD alone. Besides, succinate dehydrogenase activity also was improved when L-glutamine was administrated before cantharidin compared to cantharidin. CONCLUSIONS: This study provided evidence that L-glutamine could protect cardiac cells against the acute cantharidin-induced cardiotoxicity and the protective mechanism of glutamine may be related to the myocardial cell membrane or the tricarboxylic acid cycle in the mitochondria.

Unique Responses of Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines toward Cantharidin and Norcantharidin.

The present study aimed to investigate whether cell lines from human gastric and liver cancers respond differently toward cantharidin (CTD) and norcantharidin (NCTD) than other types of cancer cells. We first established the half maximal inhibitory concentrations (IC50s) of CTD for a large panel of cancer cell lines representing the 12 major types of human cancers and the mode of cell death induced by the two compounds. We next compared the growth inhibitory effects as well as the corresponding modes of action of CTD and NCTD. The IncuCyte ZOOM system was used as a semi-high throughput means to define IC50s and 90% inhibitory doses (IC90s) as a reference for the maximal tolerable doses (MTDs) for the two compounds in 72 cancer cell lines. Classical clonogenic survival assay was used to assess the anti-proliferative effect of CTD on selected cell lines of interest. In addition, DNA content-based flow was used to interrogate the modes of cell death following CTD or NCTD exposure. The results of these experiments led to several findings. 1). Cell lines representing hepatocellular carcinomas (HCCs) and cholangiocarcinomas (CCs) were among the most sensitive toward CTD, consistent with the previous clinical study of this compound and its source of origin, Mylabris. 2). Among the individual cell lines of a given cancer types, the sensitivity trends for CTD and NCTD did not exhibit a good correlation. 3) CTD and NCTD caused distinctive cytotoxic effects on HepG2 cells. Specifically, while a cytostatic effect is the primary cause of growth inhibition of CTD, cytotoxic effect is the main contributing factor for the growth inhibition of NTCD. These results indicate that liver cancer cell lines are among the most sensitive to CTD and that CTD and NCTD exhibit their effects through distinct mechanisms.

A new bioluminescent imaging technology for studying oxidative stress in the testis and its impacts on fertility.

PURPOSE: Excessive oxidative stress (OS) leads to cellular dysfunctions and cell death and constitutes a major cause of male infertility. However, the etiologies of increased reactive oxygen species (ROS) in male infertility is not fully understood. One major limitation is the lack of an in vivo imaging system that can be used to effectively study the impact of excessive ROS in the testis. Recently, we discovered that the hepatocellular carcinoma reporter (HCR) mice previously generated in our laboratory also expressed luciferase in the spermatids of the testis. The goal of the current study is to use the HCR mice to detect OS in the testis and to investigate the potential use of this new system in studying OS-induced male infertility. EXPERIMENTAL DESIGN: Bioluminescence imaging (BLI) was performed in HCR mice that were treated with peroxy caged luciferin-1 (PCL-1), an OS reporter, to establish a new mouse model for in vivo monitoring of the OS status inside the male reproductive tract. Subsequently, the effect of acetaminophen (APAP) overdose on the OS inside the testis and male fertility were determined. Lastly, APAP was co-administered with glutathione, an antioxidant reagent, to test if the HCR mice can serve as a model for the effective and rapid assessment of the potency of individual agents in modifying the OS inside the mouse testis. RESULTS: The OS level in the testis in the HCR mice was readily detected by BLI. The use of this new model led to the discovery that APAP caused a sudden rise of OS in the testis and was a potent toxicant for the male reproductive system. Moreover, administration of glutathione was effective in preventing the APAP-induced elevation of OS and in ameliorating all of the OS-induced anomalies in the testis. CONCLUSIONS: The HCR mice represent an excellent model for monitoring OS change in the mouse testis by real time BLI. APAP is a potent male reproductive toxicant and APAP-treated mice represent a valid model for OS-induced male infertility. This model can be used to study OS-induced damage in male reproductive tract and in assessing the effects of therapeutic agents on the relative levels of OS and male fertility.

Does the Fragrance of Essential Oils Alleviate the Fatigue Induced by Exercise? A Biochemical Indicator Test in Rats.

OBJECTIVE: To study the effect of the essential oils of Citrus sinensis L., Mentha piperita L., Syzygium aromaticum L., and Rosmarinus officinalis L. on physical exhaustion in rats. METHODS: Forty-eight male Wistar rats were randomly divided into a control group, a fatigue group, an essential oil mixture (EOM) group, and a peppermint essential oil (PEO) group. Loaded swimming to exhaustion was used as the rat fatigue model. Two groups were nebulized with EOM and PEO after swimming, and the others were nebulized with distilled water. After continuous inhalation for 3 days, the swimming time, blood glucose, blood lactic acid (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in blood were determined. RESULTS: While an increased time to exhaustion and SOD activity were apparent in both the EOM and PEO groups, the BLA and MDA were lower in both groups, in comparison with the fatigue group, and the changes in the EOM group were more dramatic. Additionally, the EOM group also showed marked changes of the rise of blood glucose and the decrease of BUN and GSH-PX. CONCLUSION: The results suggested that the inhalation of an essential oil mixture could powerfully relieve exercise-induced fatigue.