Effects of long-term oral administration of polymeric microcapsules containing tyrosinase on maintaining decreased systemic tyrosine levels in rats.
There is no effective treatment for melanoma, a fatal skin cancer occurring with increasing frequency. Dietary tyrosine restriction lowers systemic tyrosine and suppresses the growth of melanoma in mice, but this is not tolerated by human resulting in nausea, vomiting, and weight loss. We report here the successful use of oral polymeric microcapsules containing tyrosinase to lower the systemic tyrosine level in the rats. We found that microencapsulated tyrosinase incubated with intestinal content of rats selectively lowered the tyrosine level. We then studied the daily oral administration of microencapsulated tyrosinase in rats of one dose a day, two doses a day, and three doses a day over a period of up to 22 days. With three doses a day, the tyrosine levels in the test group decreased to 68.8% of the control group by day 4 and then decreased to 52.6% after this and remained at this level throughout the 22 days test period. This is the level shown earlier by other workers using dietary restriction of tyrosine to result in suppression of growth of melanoma. However, unlike dietary tyrosine restriction, oral tyrosinase microcapsules did not result in adverse effects nor significant differences in growth (weight gain) when compared to the control group. This approach can also be used for the lowering of systemic tyrosine in hypertyrosinemia, an inborn error of metabolism.
Yu
Binglan
B
Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, 3655 Drummond Street, Rm 1006, Montreal, Quebec, Canada H3G 1Y6.
Chang
Thomas Ming Swi
TM
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002214:Capsules; D004339:Drug Compounding; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008297:Male; D014442:Monophenol Monooxygenase / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000097:blood*
D002214:Capsules; D014443:Tyrosine; D014442:Monophenol Monooxygenase