Antidepressant Like Effect of Sodium Orthovanadate in A Mouse Model of Chronic Unpredictable Mild Stress.

Depression is a psychiatric disorder characterized by low esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling be associated with depression. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Various behavioral tests like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured every week. Depressive-like behavior was associated with increased oxidative stress in the brain and subsequent reduction of BDNF. Further, sodium orthovanadate (SOV), a protein tyrosine phosphatase inhibitor was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) was given to mice orally for 21 days before 30 minutes of stress induction. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by both SOV and fluoxetine. SOV at 10 mg/kg has demonstrated significant results in our study by decreasing malondialdehyde levels (MDA/LPO), NO levels, and increasing GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups (SOV-5 mg/kg, 10 mg/kg, and FLX-10 mg/kg) as compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Decreased serum corticosterone levels (SOV-5 mg/kg, 10 mg/kg); FLX (10 mg/kg) + SOV (5 mg/kg); FLX-10 mg/kg and per-se) and elevated BDNF level (SOV-5 mg/kg, 10 mg/kg and FLX-10 mg/kg) were associated with attenuation of depressive-like behavior. The findings of this preliminary study indicate that SOV has the potential to restore antidepressant-like effect or prevention of stress-induced anhedonia and so further molecular mechanisms will be warranted for clinical translation.

Neuroprotective Potential of Sodium Orthovanadate in a Mouse Model of Chronic Unpredictable Mild Stress.

Depression is a psychiatric disorder characterized by low-esteem, anhedonia, social deficit, and lack of interest. Decreased BDNF and impaired TrKB signaling have been found to be associated in depression. Moreover, oxidative stress in the brain and subsequent reduction of BDNF have a prominent role in psychiatric disorders. In our study, depressive-like behavior was induced in mice by chronic unpredictable mild stress (CUMS) model. Further, sodium orthovanadate (SOV), a protein tyrosine phospahatase was used as a test drug as it is reported to stimulate BDNF levels. Sodium orthovanadate (SOV-5 mg/kg, 10 mg/kg) and fluoxetine (10 mg/kg) were given to mice orally for 21 days prior 30 minutes of stress induction. Various behavioral studies like tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT); biochemical analyses for corticosterone, reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), nitric oxide (NO) and ELISA for BDNF were performed. Body weight was measured on a weekly basis. The behavioral tests reflected depressive-like behavior in CUMS, which was attenuated by SOV and fluoxetine. SOV (10 mg/kg) significantly decreased malondialdehyde levels, NO, whereas increased GSH and SOD in both the cortex and hippocampus. Besides, ELISA revealed the elevation of BDNF levels in the treatment groups compared with the disease group (CUMS). Therefore, the treatment with SOV appeared to reverse both oxidative and nitrosative stress. Elevated BDNF level was associated with attenuation of depressive-like behaviors and serum corticosterone levels. The findings of this preliminary study indicates that SOV has potential to restore mood and social interaction in depression and so further molecular mechanisms will be warranted for clinical translation.

Effect of sodium orthovanadate on ovulation isolated ovarian follicles in Siberian Sturgeon (Acipenser baerii) In Vitro

Effects of sodium orthovanadate on oocyte ovulation were examined during in vitro culture of Siberian sturgeon ovarian follicles from hibernating fish. It was shown that sodium orthovanadate stimulates ovulation of Siberian sturgeon oocytes in a dose-dependent manner. The stimulating or inhibitory effect of vanadate depends on the time of addition to the incubation medium. It was also shown that the stimulating effects of orthovanadate depend on the physiological status of hibernating females whose oocytes were isolated

17-Allylamino-demethoxygeldanamycin Used Alone or in Combination with Sodium Orthovanadate Promotes Apoptosis and Inhibits Invasion of SH-SY5Y Cells by Modulating PIWIL2

Neuroblastoma (NB) is one of the most common extracranial solid tumors of childhood and accounts for 15% of cancer deaths. Even with the multimodality treatment protocols, the advanced-stage tumor overall 5-year survival rate is less than 50%. Therefore, novel drug therapy targeting cellular signal transduction pathways regulating the apoptotic cascade may be important for the treatment of drug-resistant NB. In our previous studies, we have demonstrated that 5 μM sodium orthovanadate (SOV) induced the apoptosis of SH-SY5Y cells. 17-Allylamino-demethoxygeldanamycin (17-AAG) is a geldanamycin- (GA-) derived heat shock protein 90 (Hsp90) inhibitor, and it has been shown to have potent antitumor activity in head and neck cancers. However, the effect of 17-AAG on the apoptosis of NB cells has not been reported. Therefore, the purpose of this study was to determine the effects of 17-AAG and SOV on the growth and invasion of SH-SY5Y cells in vitro and explore the related mechanism. In this study, we first investigated the antiviability effect of 17-AAG on SH-SY5Y cells, then studied the cell apoptosis and invasion influenced by 17-AAG and SOV, and assessed the role of PIWI-Like2 (PIWIL2) and piRNA-PIWI signaling in it. The results showed that 5 μM 17-AAG inhibited cell growth and viability and induced apoptosis in SH-SY5Y cells. Both 17-AAG and SOV reduced the level of PIWIL2 and Bcl-xl proteins and inhibited the invasion of SH-SY5Y cells. In addition, the combined use of the two drugs had greater effect than the single use of any drug.

Inactivation of H+-ATPase Participates in the Influence of Variation Potential on Photosynthesis and Respiration in Peas

Local damage (e.g., burning, heating, or crushing) causes the generation and propagation of a variation potential (VP), which is a unique electrical signal in higher plants. A VP influences numerous physiological processes, with photosynthesis and respiration being important targets. VP generation is based on transient inactivation of H+-ATPase in plasma membrane. In this work, we investigated the participation of this inactivation in the development of VP-induced photosynthetic and respiratory responses. Two- to three-week-old pea seedlings (Pisum sativum L.) and their protoplasts were investigated. Photosynthesis and respiration in intact seedlings were measured using a GFS-3000 gas analyzer, Dual-PAM-100 Pulse-Amplitude-Modulation (PAM)-fluorometer, and a Dual-PAM gas-exchange Cuvette 3010-Dual. Electrical activity was measured using extracellular electrodes. The parameters of photosynthetic light reactions in protoplasts were measured using the Dual-PAM-100; photosynthesis- and respiration-related changes in O2 exchange rate were measured using an Oxygraph Plus System. We found that preliminary changes in the activity of H+-ATPase in the plasma membrane (its inactivation by sodium orthovanadate or activation by fusicoccin) influenced the amplitudes and magnitudes of VP-induced photosynthetic and respiratory responses in intact seedlings. Decreases in H+-ATPase activity (sodium orthovanadate treatment) induced fast decreases in photosynthetic activity and increases in respiration in protoplasts. Thus, our results support the effect of H+-ATPase inactivation on VP-induced photosynthetic and respiratory responses.

Sodium orthovanadate inhibits growth of acute leukemia HL60 cells and HL60/A cells in vitro

Vanadium is an ultratrace element. The transition metal vanadium, widely exists in the environment and exhibits various biological and physiological effects in the human body, yet with no presently known specific physiological function in mammals. Sodium orthovanadate (SOV) is a kind of vanadium compound. SOV has shown promising antineoplastic activity in several human cancers. But the effects of SOV on acute promyelocytic leukemia (APL) are still unknown. In the present study, for the first time, we found that SOV could inhibit proliferation, induce G2/M cell cycle arrest and apoptosis, and could inhibit autophagy of acute leukemia cell lines in vitro. Thus, our findings suggest that SOV could effectively suppress the growth of acute leukemia HL60 cells and HL60/A cells through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in APL treatment.