Efeito da administração aguda e crônica de metionina e/ou metionina sulfóxido na atividade de enzimas dos sistemas purinérgico e colinérgico e sobre parâmetros inflamatórios em linfócitos e soro de ratos jovens

Abstract

Elevation of plasma methionine (Met) and its metabolites may occur in several genetic abnormalities, such as methionine adenosyltransferase deficiency, causing a broad spectrum of physiological disorders. ATP is involved in proinflammatory functions while adenosine and acetylcholine have anti-inflammatory effects. The action of these molecules at the site of inflammation is controlled mainly by enzymes such as NTPDase, Adenosine Deaminase (ADA), Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuchE). In the present study we investigated the effect of acute and chronic treatment with Met and/or methionine sulfoxide (MetO) on ectonucleotidase and cholinesterase activity and on the levels of C - reactive protein (CRP) and interleukin 10 (IL-10) in lymphocytes and serum of young rats. The animals were divided into four groups: I (control); II (Met); III (MetO) and IV (Met plus MetO). In the acute protocol, Met and MetO were administrated as a single subcutaneous injection and the animals were submitted to euthanasia 1 h or 3 h after treatment. In the chronic protocol Met and/or MetO were administered to animals twice a day with an interval of 8h between injections, during 21 days. The results showed that ATP hydrolysis was decreased in lymphocytes 1 h after the treatment of the animals of groups III and IV (P<0.05). Conversely, an increase in ATP and ADP hydrolysis in lymphocytes was observed in groups III and VI, and an increase in ADA activity in group III 3 h after the amino acids administration (P<0.05). No alterations in the NTPDase and ADA activities were observed in lymphocytes and serum in chronic treatment. AChE activity also was increased in lymphocytes 3 h and 21 days after treatment in the animals of groups III e IV (P<0.05) while BUChE activity was decreased 1 h and 21 days after treatment in the same groups (P<0.05). In chronic treatment, an increase in the levels of CRP was observed in the serum of rats treated with MetO or an association of Met plus MetO and a decrease in the IL-10 levels in animals treated with Met, MetO and Met plus MetO when compared to the control group (P<0.05).Our results demonstrated that inflammatory parameters are altered mainly in MetO treatment. The changes caused in the purinergic and cholinergic system and in, anti-inflammatory cytokines may contribute to understanding the inflammatory alterations observed in hypermethioninemic patients.