Doses Of Methionine Sulfoximine Research Articles

In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice

We investigated the relationship between brain glycogen anabolism and methionine sulfoximine (MSO)-induced seizures in two inbred mouse strains that presented differential susceptibility to the convulsant. CBA/J was considered a MSO-high-reactive strain and C57BL/6J a MSO-low-reactive strain. Accordingly, the dose of MSO needed to induce seizures in CBA/J mice is lower than that in C57BL/6J mice, and CBA/J mice which had seizures, died during the first convulsion. In addition, the time–course of the MSO effect is faster in CBA/J mice than that in C57BL/6J mice. Analyses were performed in C57BL/6J and CBA/J mice after administration of 75 (subconvulsive dose) and 40 mg/kg of MSO (subconvulsive dose, not lethal dose), respectively. In the preconvulsive period, MSO induced an increase in the brain glycogen content of C57BL/6J mice only. Twenty-four hours after MSO administration, the brain glycogen content increased in both strains. The activity and expression of fructose-1,6-bisphosphatase, the last key enzyme of the gluconeogenic pathway, were increased in MSO-treated C57BL/6J mice as compared to control mice, at all experimental time points, whereas they were increased in CBA/J mice only 24 h after MSO administration. These latter results correspond to CBA/J mice that did not have seizures. Interestingly, the differences observed in vivo were consistent with results in primary cultured astrocytes from the two strains. This data suggests that the metabolism impairment, which was not a consequence of seizures, could be related to the difference in seizure susceptibility between the two strains, depending on their genetic background.

Liver glutamine synthetase activity and time courses of blood and urinary nitrogenous compounds after injection of methionine sulfoximine at various dosages in chickens fed a low protein diet.

Methionine sulfoximine (MSM) was injected into chickens fed 5% protein diet at dosages of 20, 50, 75 and 100mg/kg body wt. The remaining activity of liver glutamine synthetase 7hr after dosing decreased with an increase of its dose, ranging from 12% to 6% of the control activity. The decreased plasma glutamine concentration 1.5hr after MSM treatment or later became low as a dose of MSM was increased. Blood ammonia concentration sharply increased up to 2.5hr after a transient unchange or fall and reached the steady state level at 4.5hr which was in proportion to MSM-dose. At 4.5hr the blood ammonia concentration was inversely correlated with plasma glutamine concentration (r=0.679). The rate of urinary excretion of ammonia rapidly increased for the first 3-4hr in similar manners and magnitudes in all chickens treated with MSM except 20mg MSM-dose. Almost the same time course patterns of plasma uric acid or urinary uric acid excretion in the doses of 50, 75 and 100mg tended to be low between 1 and 4hr after dosing as compared with 20mg MSM-dosed and control chickens. Any doses of MSM gave no effect on excretion of total urinary nitrogen. It is concluded that each of the time courses of blood glutamine, ammonia and uric acid and of urinary ammonia, uric acid and total nitrogen responds to a dose of MSM in similar manners at low and high protein intakes.