The Methionine Sulfoximine Syndrome in the Cat

Abstract

SUMMARY Methionine sulfoximine, the toxic principle of the agenized protein diet, produces in the cat a complex syndrome characterized by behavioral and convulsive changes. In a series of 50 cats, the following features were most consistently observed: Sniffing movements, involving the upper lip, nose and lower eyelid, and accompanied by profuse salivation and impairment of consciousness. Episodic behavioral changes consisting of head‐turning, sniffing, and crouching movements strongly suggesting apprehension, orientation and fear. Running fits at the onset of which the animal may appear fearful or hysterical. Generalized tonic‐clonic convulsions. A detailed description of the syndrome is given and the influence of external stimuli and such factors as dosage of toxic agent, age, nutritional status of experimental animal, upon the character, frequency, rapidity of onset, and duration of the various behavioral and convulsive phenomena are discussed. The significance of the sulfoximine syndrome, as regards its biochemical and behavioral similarities to certain types of human epilepsy and its value as an experimental tool i n the investigation of the patho‐physiology of seizures are discussed. RÉUMÉ La méthionine sulfoximine, principe toxique du régime de protéine agénisée, produit chez le chat un syndfrome complexe charactérisé par des changements du comportement et des convulsions. Les caractéristiques suivants ont été constamment observées sur une série de 50 chats: Mouvements de reniflument comprenant la lèvre supérieure, le nez et la paupière inférieure, accompagnés de salivation profuse et d'abaissement de la conscience. Des changements épisodiques du comportement consistant en tournement de la těte, reniflement et mouvements de rampement donnant fortement l'impression de crainte, d'orientation et d'appréhension. Accès de course folle au début desquels l'animal peut sembler très craintif ou hystérique. Convulsions toniques‐cloniques généralisées. L'auteur donne une description détaillée du syndrome et décrit l'influence de stimuli externes et celle de facteurs tels que le dosage d'un agent toxique, de l'ǎge et de l'état de nutrition de l'animal d'expérience, sur le caractère, la fréquence et la rapidité du début de la crise, la durée du changement du comportment et des phénomènes convgulsifs. La significatin du syndrome de la sulfoximine fait l'objet d'une discussion en ce qui concerne les similitudes biochimiques et celles du comportement à l'endroit de certains types d'épilepsie humaine ainsi que sa valeur en tant qu'instrument d'expérience dans des recherches sur la pathophysiologie des crises.

Inhibition of Mycobacterium tuberculosis Glutamine Synthetase as a Novel Antibiotic Strategy against Tuberculosis: Demonstration of Efficacy In Vivo

“…In contrast to dogs, humans fed large amounts of agenized food exhibited no significant clinical, electroencephalographic, or biochemical abnormalities (13,15). If humans can tolerate higher doses of MSO than guinea pigs, greater efficacy against tuberculosis may be achievable in humans than in guinea pigs with this agent.…”

“…In one study, an injection of 3 mg of racemic D,L-methionine-SR-sulfoximine kg Ϫ1 , about one-half the potency of the MSO isomer used here, was lethal to dogs, whereas an injection of 100 to 150 mg kg Ϫ1 produced no ill effects in monkeys and rats (4). Previous studies of the susceptibility of animals to agenized (nitrogen trichloridetreated) food suggested that guinea pigs were less sensitive to MSO than dogs (15). However, in our study, guinea pigs appeared highly sensitive to repeatedly administered MSO, as the maximum tolerated daily doses were only 3 mg kg Ϫ1 in uninfected animals and 1.5 mg kg Ϫ1 in infected animals.…”

“…MSO is a known epileptogenic agent, a property first observed in dogs fed biscuits contaminated with MSO (15). The biscuits were contaminated because they were made from flour bleached with nitrogen trichloride or agene, a common practice in the first half of the 20th century.…”

Functional Analysis of GlnE, an Essential Adenylyl Transferase in Mycobacterium tuberculosis

“…MetSox has wide activity against GS enzymes and demonstrates strong inhibition of all four M. tuberculosis GSs. However, MetSox itself cannot be used as an antitubercular agent due to its epileptogenic properties (28).…”

Retrospective evaluation of methionine intoxication associated with urinary acidifying products in dogs: 1,525 cases (2001–2012)

“…Single toxic doses of methionine have been used in feline experimental studies because methionine toxicosis can cause recurrent grand mal seizures in cats consistent with those seen in epileptic people . Doses of 0.5–1.0 g/kg of methionine per day for multiple days were found to induce Heinz body anemia and methemoglobinemia in cats .…”