Transport of cycasin by the intestinal Na+/glucose cotransporter

Damage and Repair of Nerve Cell Dna in Toxic Stress*

“…Unlike BMAA [41,42], cycasin and MAM readily cross the blood-brain barrier with ϳ5% of either administered agent detected in brain tissue (GK, unpublished data; [43]) ( Table 1). Depending on the route (i.e., oral or topical) of cycad exposure, cycasin gains access to brain tissue via a high-capacity brain endothelial [44,45] or intestinal [46] Na ϩ -dependent glucose transporter (SGLT). Cycasin shows a 100 times greater affinity for the brain endothelial SGLT, suggesting that the genotoxin is rapidly transported by the brain SGLT before it liberates MAM, presumably by enzymatic action of cytosolic (neutral) β-glucosidase.…”

Environmental Neurotoxins Linked to a Prototypical Neurodegenerative Disease

“…Because the neurotoxic properties of cycasin and its active metabolite MAM are poorly understood, initial studies by our group examined the distribution, uptake, and metabolism of cycasin and its active metabolite MAM in rodents. Depending on the route of exposure (topical or oral), cycasin gains entry into the brain by a high-affinity brain endothelial [137] or intestinal [138] Na + -dependent glucose transporter (SGLT). Depending on the route of exposure (topical or oral), cycasin gains entry into the brain by a high-affinity brain endothelial [137] or intestinal [138] Na + -dependent glucose transporter (SGLT).…”

Cycadaceae L.

“…However, in these studies the effect occurred only with oral or parenteral administration in the fi rst 24 hours after birth. There is an active transport mechanism for cycasin across the intestinal mucosa via the Na + /glucose transporter (Hirayama et al 1994), but whether there are factors or conditions that promote access to the central nervous system in adults is not clear. Similar effects have been produced in several animal species, although susceptibility and manifestations vary (Haddad et al 1972).…”