Different pathways involved in the stimulatory effects of homocysteine on rat duodenal smooth muscle

Abstract

Recent studies have confi rmed that hyperhomocysteinemia is associated with gastrointestinal diseases; however, the direct effect of homocysteine on gastrointestinal reactivity still remains unknown. The aim of this study was to demonstrate how homocysteine may affect nitric oxide mediated duodenal relaxation and whether cholinergic receptors and K + channels take part in stimulating motility, as well as to explore whether oxidative stress is associated with homocysteine-mediated effects. Experiments were carried out on male rats, body mass 250-300 g. Two groups of animals were treated by i.p. application of saline and D,L-Hcy (0.6 μmol/g bm). After 2h of incubation, the duodenal segments were prepared for biochemical analysis and contractile response measurements in an organ bath with Tyrode's solution. Effects of TEA (10 mmol/L) and L-NAME (30 μmol/L) on duodenal contractility in the presence of D,L-Hcy (0.6 μmol/g bm) were investigated. Elevated homocysteine levels seem to be of crucial importance for the deterioration of contractility through nitric oxide mediated relaxation, and, in part, by activation of K + channels. Hcy showed direct promuscarinic effects, since 30 min pretreatment of rat duodenum signifi cantly enhanced the contractile effect of increasing concentrations of ACh (10 -9 -10 -2 mol/L). Catalase activity, superoxide dismutase, glutathione peroxidase and the total antioxidant system were reduced while the thiobarbituric acid-reactive substances level was elevated. Our data showed a consistent profi le of gastrointestinal injury elicited by sulfur-containing amino acid-homocysteine. This could contribute to explain, at least in part, the mechanisms involved in human gastrointestinal diseases associated to hyperhomocysteinemia.

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems

“…Quite similar effects were achieved in liver tissue, where Cys and NAC improved antioxidative defense by increasing the activity of antioxidant enzymes and decreased tissue damage induced by subchronic methionine exposure (Stojanović et al 2018b). On the other hand, HHcy induced by methionine as well as DL-Hcy TLHC in acute administration had opposite effect in mentioned tissues(Stojanović et al 2016b, Stojanović et al 2017. component of several disorders including cardiovascular and cerebrovascular diseases, neurodegeneration, liver steatosis, hyperhomocysteinemia can result from deficiencies of vitamin cofactors (B 6 , B 12 , folic acid) required for Hcy metabolism and/or from genetic disorders of its metabolism.…”