Methionine and methionine sulfoxide alter parameters of oxidative stress in the liver of young rats: in vitro and in vivo studies

Abstract

It has been shown that elevation of plasma methionine (Met) and its metabolites may occur in several genetic abnormalities. In this study we investigated the in vitro and in vivo effects of the Met and methionine sulfoxide (MetO) on oxidative stress parameters in the liver of rats. For in vitro studies, liver homogenates were incubated with Met, MetO, and Mix (Met + MetO). For in vivo studies, the animals were divided into groups: saline, Met 0.4 g/kg, MetO 0.1 g/kg, and Met 0.4 g/kg + MetO 0.1 g/kg. The animals were euthanized 1 and 3 h after injection. In vitro results showed that Met 1 and 2 mM and Mix increased catalase (CAT) activity. Superoxide dismutase (SOD) was enhanced by Met 1 and 2 mM, MetO 0.5 mM, and Mix. Dichlorofluorescein oxidation was increased by Met 1 mM and Mix. In vivo results showed that Met, MetO, and Mix decreased TBARS levels at 1 h. Total thiol content decreased 1 h after and increased 3 h after MetO and Met plus MetO administrations. Carbonyl content was enhanced by Met and was reduced by MetO 1 h after administration. Met, MetO and Met plus MetO decreased CAT activity 1 and 3 h after administration. Furthermore, only MetO increased SOD activity. In addition, Met, MetO, and Mix decreased dichlorofluorescein oxidation at 1 and 3 h. Our data indicate that Met/MetO in vivo and in vitro modify liver homeostasis by altering the redox cellular state. However, the hepatic changes caused by these compounds suggest a short-time adaptation of this tissue.

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

“…When ROS production is high, homeostasis is disturbed, leading to oxidative stress, which has a key role in the development of liver and other chronic diseases (5,6). Oxidative stress generates liver damage by causing changes in lipids, proteins and DNK molecules and even more importantly, by modifying pathways that control normal biological functions.…”

“…limiting the production of reactive oxygen species (6,7). Methionine removes metabolic waste products from the liver and can thus decrease the risk of hepatic and arterial steatosis.…”

“…The hyperhomocysteinemia induced by methionine administration leads to increased production of free radicals and inflammation markers in macrophages of the mouse peritoneum (5). An in vitro and in vivo study on rats showed the alteration of oxidative stress parameters after the methionine administration (6), and hemosiderin accumulated in rat hepatocytes after a four-week methionine treatment (7). The occurrence of hyperhomocysteinemia was also reported in a population of patients with inflammatory bowel disease after an oral overload with methionine (8).…”

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

“…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.…”

Protective impact of N-acetyl-L-cysteine on methionine stimulatory effects in rat colon

“…In vitro i in vivo studija na pacovima pokazala je alteraciju parametara oksidativnog stresa nakon primene metionina (17). Oksidativni stres ima važan uticaj na zapaljenje preko aktiviranja redoks osetljive transkripcije faktora poput nuklearnog faktora kB (NF -kB) i aktivatora proteina 1, koji regulišu ekspresiju ključnih gena tako što kodiraju proinflamatorne medijatore i zaštitne antioksidativne proteine (18).…”