Methionine and/or Methionine Sulfoxide Alter Ectoenzymes Activities in Lymphocytes and Inflammatory Parameters in Serum from Young Rats: Acute and Chronic Effects

Abstract

In this study we investigated the effect of acute and chronic treatment with Met and/or methionine sulfoxide (MetO) on ectonucleotidases and cholinesterases activities from lymphocytes and purine derivatives compounds, C-protein reactive, interleukin-10, interleukin-6, and tumor necrosis factor-α levels in serum of young rats. Adenosine triphosphate hydrolysis was decreased in lymphocytes 1 h after treatment by MetO and Met + MetO. However, adenosine triphosphate and adenosine diphosphate hydrolysis in lymphocytes was increased in the groups MetO and Met + MetO and adenosine deaminase activity was increased in MetO 3 h after the treatment. Acetylcholinesterase activity was increased in lymphocytes after 3 h and 21 days of treatment by MetO and Met + MetO, while serum butyrycholinesterase activity was decreased after 1 h and 21 days of treatment in the same groups. In chronic treatment, interleukin-6 and tumor necrosis factor-α level were increased, while that interleukin-10 level was decreased by Met, MetO, and Met + MetO when compared to control group. C-protein reactive level was increased by MetO and Met + MetO. Adenosine triphosphate and adenosine monophosphate levels were reduced in all amino acids treated groups, while adenosine diphosphate and hypoxanthine were enhanced by MetO and Met + MetO. Adenosine and xanthine were reduced in the MetO group, whereas inosine levels were decreased in the MetO and Met + MetO groups. These findings help to understand the inflammatory alterations observed in hypermethioninemia.

High levels of methionine and methionine sulfoxide: Impact on adenine nucleotide hydrolysis and redox status in platelets and serum of young rats

“…However, our research group has shown that MetO administration decreases Ado levels in serum with chronic treatment. 10 Taken together, these findings suggest that both acute and chronic treatment with Met and its metabolite MetO could alter platelet function by interfering with Ado levels. Previous studies have demonstrated that Met and MetO increase the levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α and alter cholinergic and purinergic enzyme activity in lymphocytes of young rats.…”

“…A single subcutaneous injection of Met and/or MetO was administered, and the control rats received an equivalent volume of saline. Five animals from each group were anesthetized with isoflurane and euthanized by cardiac puncture 1 hour after injection, and the remaining five animals were euthanized 3 hours after the amino acid treatment . Blood was collected by cardiac puncture (Figure A).…”

“…Forty 6‐day‐old rats weighing 10 to 15 g were divided into four groups (n = 10): group I (control), group II (treated with Met), group III (treated with MetO), and group IV (treated with Met + MetO). Met and MetO doses administered were chosen to induce high plasma levels similar to those found in patients affected by hypermethioninemia as described by previous studies . Met and MetO were administered to rats subcutaneously twice a day with an interval of 8 hours between injections from day 6 to 28, as described previously by Stefanello et al Animals of groups II and III received 0.2 g/kg of Met or 0.05 g/kg of MetO during the first 8 days of treatment, 0.3 g/kg of Met or 0.075 g/kg of MetO from day 15 to 21, and 0.4 g/kg of Met or 0.1 g/kg of MetO from days 22 to 28.…”

“…Five animals from each group were anesthetized with isoflurane and euthanized by cardiac puncture 1 hour after injection, and the remaining five animals were euthanized 3 hours after the amino acid treatment. 6,10,17 Blood was collected by cardiac puncture ( Figure 1A).…”

“…Met and MetO doses administered were chosen to induce high plasma levels similar to those found in patients affected by hypermethioninemia as described by previous studies. 6,10,17 Met and MetO were administered to rats subcutaneously twice a day with an interval of 8 hours between injections from day 6 to 28, as described previously by Stefanello et al 17 Animals of groups II and III received 0.2 g/kg of Met or 0.05 g/kg of MetO during the first 8 days of treatment, 0.3 g/kg of Met or 0.075 g/kg of MetO from day 15 to 21, and 0.4 g/kg of Met or 0.1 g/kg of MetO from days 22 to 28. The animals of group IV received a combination of Met and MetO, whereas control rats (group I) received saline solution in the same volumes.…”