Omega-3 fatty acids supplementation with lithium and aripiprazole for improving the balance of circulating hormones and brain neurotransmitters in manic mice model.

The present study was designed to evaluate the combined effect of lithium and aripiprazole supplemented with omega-3 fatty acids in methylphenidate (MPD)-induced manic mice. Swiss albino mice were administered with MPD or saline for 14 days, and based on changes in behavioral activities animals were treated with lithium, aripiprazole, and omega-3 fatty acids from the 8th day. Behavioral patterns were analyzed by video tracking. Thyroxine, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were assayed in serum using ELISA kits. The levels of neurotransmitters in the whole brain were analyzed spectrofluorometrically. Glycogen synthase kinase 3ß (GSK3ß) mice brain mRNA expression levels and phosphorylated Akt (pAkt) protein levels were measured using RT-PCR and western blot, respectively. Results indicated that the administration of MPD alters the behavioral activity, thyroid hormones, FSH, LH, and testosterone levels. Lithium, aripiprazole, and omega-3 fatty acids alone significantly reduced MPD-induced behavior, hormonal, and neurotransmitter abnormalities. However, GSK3ß and pAkt in the brain showed no significant differences in the level of expression. These results reveal that the combination of lithium and aripiprazole supplemented with omega-3 fatty acids provide protective effects against MPD-induced neuroendocrine system and multiple neurochemical abnormalities.

Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania.

Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice.

Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic transdifferentiation of aortic VSMC in CRF rats.

Cardiovascular dysfunction and vascular calcification is the leading cause of death in chronic renal failure (CRF) patients. This study was designed to evaluate the effect of diosgenin on coronary flow resistance and to address the question whether the previously proven antivascular calcification potential of diosgenin is associated or not with the osteochondrogenic transdifferentiation of vascular smooth muscle cells (VSMC). In this study, CRF in Wistar rats was induced by fed with 0.75% adenine and diosgenin was treated everyday at the dose of 40 mg/kg. Langendorff based isolated heart protocol was employed to analyze the coronary flow resistance. Western blot method was used to explore the phosphorylation dynamics of endothelial nitric oxide synthase (eNOS) at the serine 1177 residue. In addition, cardiac nitric oxide metabolites level also assessed. Quantitative expression of VSMC and osteochondrogenic markers was also evaluated. Antioxidant potential of diosgenin was studied in vitro. The outcome of the present study explores that diosgenin treatment significantly improves the coronary resistance and increased the nitric oxide metabolites level compared with CRF. Further, diosgenin increases the phosphorylation of eNOS (peNOS ser1177). Moreover, diosgenin reduced the aortic expression of osteochondrogenic markers and improved the VSMC phenotype components. Further, diosgenin shows concentration dependent antioxidant potential. In conclusion, this study have proven that diosgenin have enough potential to improve the coronary function and interfere the osteochondrogenic transdifferentiation program of aortic VSMC which supports its antivascular calcification potential.