Adenosine 5'-triphosphate disodium salt - CAS 987-65-5

Mitochondrial complex I appears to be dysfunctional in progressive supranuclear palsy (PSP). Coenzyme Q(10) (CoQ(10)) is a physiological cofactor of complex I. Therefore, we evaluated the short-term effects of CoQ(10) in PSP. We performed a double-blind, randomized, placebo-controlled, phase II trial, including 21 clinically probable PSP patients (stage < or = III) to receive a liquid nanodispersion of CoQ(10) (5 mg/kg/day) or matching placebo. Over a 6-week period, we determined the change in CoQ(10) serum concentration, cerebral energy metabolites (by (31)P- and (1)H-magnetic resonance spectroscopy), motor and neuropsychological dysfunction (PSP rating scale, UPDRS III, Hoehn and Yahr stage, Frontal Assessment Battery, Mini Mental Status Examination, Montgomery Asberg Depression Scale). CoQ(10) was safe and well tolerated. In patients receiving CoQ(10) compared to placebo, the concentration of low-energy phosphates (adenosine-diphosphate, unphosphorylated creatine) decreased. Consequently, the ratio of high-energy phosphates to low-energy phosphates (adenosine-triphosphate to adenosine-diphosphate, phospho-creatine to unphosphorylated creatine) increased. These changes were significant in the occipital lobe and showed a consistent trend in the basal ganglia.

Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was established using middle cerebral artery occlusion in mice. Both 62.5, 125, and 250 mg/kg oxysophoridine, via intraperitoneal injection, and 6 mg/kg nimodipine, via intragastric administration, were administered daily for 7 days before modeling. After 24 hours of reperfusion, mice were tested for neurological deficit, cerebral infarct size was assessed and brain tissue was collected. Results showed that oxysophoridine at 125, 250 mg/kg and 6 mg/kg nimodipine could reduce neurological deficit scores, cerebral infarct size and brain water content in mice. These results provided evidence that oxysophoridine plays a protective role in cerebral ischemia/reperfusion injury. In addition, oxysophoridine at 62.5, 125, and 250 mg/kg and 6 mg/kg nimodipine increased adenosine-triphosphate content, and decreased malondialdehyde and nitric oxide content. These compounds enhanced the activities of glutathione-peroxidase, superoxide dismutase, catalase, and lactate dehydrogenase, and decreased the activity of nitric oxide synthase.

Tissue levels of creatine phosphate (CP), creatine, adenosine-triphosphate(ATP), inorganic phosphate (Pi), glycogen, glucose and lactate were determined in heterotopically transplanted and recipient hearts as well as in the myocardium of sham-operated rabbitsmthe ATPase activity in these tissues was also estimatedmthe results revealed no biochemical indication of ischemic conditions in the transplanted organs relative to the other investigated tissue. The tissue levels of CP in the donor heart were even higher then in both the recipient and sham-operated organs. The concentrations of the other above listed compounds in all the studied tissue were similar throughout the first 5 post-operative days. The effect of surgery was manifested in decreased levels of CP, still prevailing 3 days post-operative in all of the investigated tissue. However, on the fifth day after surgery, the tissue concentration of CP showed a trend toward recovery. The activity of Na,K-ATPase in both donor and recipient hearts was similar. One day after surgery, the activity of the Mg-ATPase was 27% lower relative to its value on days 3 and 5 post-operatively. However no correlation was obtained between the change in Mg-ATPase and tissue concentrations of ATP.