THE EFFECTS OF ORAL ARGININE ON ITS METABOLIC PATHWAYS IN SPRAGUE-DAWLEY RATS
Kim, Raina Dain
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Oral arginine supplements are commonly used by the public for their presumed nitric oxide potentiating and vasodilatory role. However, there is a lack of clarity on the physiological impact of oral arginine on its metabolic pathways in the human body. As a versatile molecule, arginine is metabolized by multiple enzymes including arginase, nitric oxide synthase, arginine decarboxylase, and arginine:glycine amidinotransferase. Our lab has recently published a study on the physiological impact of oral arginine at a dose of 500 mg/kg/day administered for 4 weeks in male Sprague-Dawley rats. The present study examined the effects of oral L-arginine and D-arginine in 9-week-old male Sprague-Dawley rats, administered at a higher dose of 1000 mg/kg/day in drinking water for a longer duration of 16 weeks. We measured enzyme expression and activity for different enzymes, and levels of metabolites of the arginine enzymatic pathways in the urine, plasma and various organs of Sprague-Dawley rats. We also measured the expression of the primary arginine transporter, cationic amino acid transporter 1. Oral L-arginine did not alter the expression of cationic amino acid transporter 1 or the levels of arginine and lysine, which use the same transporter, in the plasma and various organs. Oral L-arginine decreased arginase expression in the ileum, and arginase activity in the plasma. It also decreased arginine:glycine amidinotransferase expression in the liver, and creatinine levels in the urine. Similarly, L-arginine supplementation decreased arginine decarboxylase expression in the ileum but increased the expression in the liver with increased plasma total polyamine levels. Interestingly, endothelial nitric oxide synthase expression was significantly increased with oral D-arginine, whereas L-arginine did not cause any significant effects in this pathway, in comparison to control. D-arginine is known to be inactive in the metabolic pathways, but surprisingly, D-arginine supplementation altered the expression of several enzymes and metabolite levels in the treated rats. In conclusion, long term oral supplementation of both L- and D-arginine significantly affected various enzymes and metabolites in the arginine metabolic pathways, as observed with a dose of 500 mg/kg/day for 4 weeks in the previous study from our lab, even though the changes differed in both studies. Determining the physiological impact of oral arginine supplements on the various metabolic pathways of arginine would allow for a better understanding of oral arginine uses, optimum dose and duration, and its safety and efficacy.
DegreeMaster of Science (M.Sc.)
CommitteeKatselis, George; Bardal, Stan; Unniappan, Suraj
Copyright DateJuly 2021