Glycine nano-selenium prevents brain oxidative stress and neurobehavioral abnormalities caused by MPTP in rats.

BACKGROUND: Parkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly. In recent years, the results of clinical and experimental studies have shown that oxidative stress is one of the important pathogenesis of PD. Selenium is one of the minor elements reported to possess antioxidant properties. Thus, the purpose of this study was to investigate the recovery effect of glycine nano-selenium on neurobehavioral abnormalities and oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rat. MATERIALS AND METHODS: SD male rats weighing 280-310 g were purchased from the Chengdu Dossy Experimental Animals Company, China. All rats were housed in a temperature-controlled room, with a 12 h light-dark cycles and had free access to food and water ad libitum. Rats were randomly divided into 4 groups with 8 animals in each group: the control group (normal saline), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine group (MPTP), MPTP + 0.05 mg/kg glycine nano-selenium (MPTP + 0.05 Se), MPTP + 0.1 mg/kg glycine nano-selenium (MPTP + 0.1 Se). Behavioral assessment, clinical symptoms, Immunohistochemistry analysis of tyrosine hydroxylase (TH) and antioxidant activity were accessed to determine the protective effects glycine nano-selenium have on PD rats. RESULTS: From the results, Rats showed a decrease in spontaneous motor behavior and an increase in pole test score. Also, the number of TH+ neurons were also significantly decreased (P < 0.05) after treated with MPTP for 7 days indicating that MPTP could successfully induce neurobehavioral abnormalities in rats. Furthermore, the lipid peroxide (MDA) levels of the PD model group were significantly increased and the antioxidant activities (SOD and GSH-PX) were significantly inhibited (P < 0.05) compared to the control group indicating the important role oxidative stress played in dopaminergic neuron death and neurobehavioral abnormalities in PD rats. Compared with the PD model group, glycine nano-selenium administration could significantly improve behavior and increase the number of TH+ neurons (P < 0.05) to protect against the loss of dopaminergic neurons. At the same time, glycine nano-selenium could decrease the MDA levels and increase the activities of SOD and GSH-PX significantly (P < 0.05). CONCLUSION: In conclusion, PD rat model was successfully developed by intraperitoneal injection of MPTP and the intragastric administration of glycine nano-selenium reduced neurobehavioral abnormalities by decreasing oxidative stress in rat brain.

Ageratina adenophora causes spleen toxicity by inducing oxidative stress and pyroptosis in mice.

Ageratina adenophora is an invasive weed with potent toxicological effects on livestock. Oxidative stress and pyroptosis play a pivotal role in regulating animal or human health and disease. The object of this study was to determine the mechanism underlying splenic toxicity induced by A. adenophora in a mouse model. Ageratina adenophora significantly increased the levels of reactive oxygen species and malondialdehyde, but decreased the antioxidants like catalase, superoxide dismutase, glutathione and glutathione peroxidase. In addition, the activity of the antioxidant enzymes was also decreased upon A. adenophora treatment. The induction of the pyroptosis pathway was evaluated in terms of the expression levels of Nod-like receptor protein 3, nuclear factor-κB, caspase-1, gasdermin-D and interleukin-1ß, all of which were significantly elevated by A. adenophora. These findings suggest that A. adenophora impairs spleen function in mice through oxidative stress damage and pyroptosis.

Involvement of mitochondrial dysfunction in hepatotoxicity induced by Ageratina adenophora in mice.

Ageratina adenophora is a noxious plant and it is known to cause acute asthma, diarrhea, depilation, and even death in livestock (Zhu et al., 2007; Wang et al., 2017). A. adenophora grows near roadsides and degraded land worldwide (He et al., 2015b). In the areas where it grows, A. adenophora is an invasive species that inhibits the growth of local plants and causes poisoning in animals that come in contact with it (Nie et al., 2012). In China, these plants can be found in Yunnan, Sichuan, Guizhou, Chongqing, and other southwestern areas (He et al., 2015a) and they have become a dominant species in these local regions. It threatens the native biodiversity and ecosystem in the invaded areas and causes serious economic losses (Wang et al., 2017). It has been reported that A. adenophora can grow in the northeast direction at a speed of 20 km per year in China (Guo et al., 2009). Because of the damage caused by A. adenophora, it ranks among the earliest alien invasive plant species in China (Wang et al., 2017).

Ageratina adenophora induces mice hepatotoxicity via ROS-NLRP3-mediated pyroptosis.

Increasing evidences have demonstrated that Ageratina adenophora (A. adenophora) can cause hepatotoxicity of animals. Liver is an important site in immune regulation and inflammatory responses. However, the information about hepatotoxicity induced by A. adenophora in relation to inflammation is still finite. To investigate the underlying mechanism, we conducted animal experiments with different dosage of A. adenophora. Mice were randomly divided into 4 groups and administrated with 0%, 10%, 20% and 30% levels of A. adenophora pallet diet in control, group A, B and C, respectively. The results showed that A. adenophora caused hepatotoxicity as revealed by increasing alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase. Then, the reactive oxygen species (ROS) levels were shown to be elicited by A. adenophora through flow cytometry assay in a dose-dependent manner. Furthermore, pyroptosis was activated by A. adenophora, which was characterized by increasing protein and mRNA levels of caspase-1, gasdermin D and interleukin-1ß. Notably, ROS down-stream factors, including nod-like receptor inflammasome protein 3 and nuclear factor-κB, were also activated by A. adenophora. These data demonstrated that A. adenophora caused liver inflammatory injury and induced hepatocyte pyroptosis by activating NLRP3 inflammasome, which was triggered by elevating ROS production levels. This research might provide new insights into the mechanism of hepatotoxicity induced by A. adenophora.