Effects of DL-Homocysteine Thiolactone on Cardiac Contractility, Coronary Flow, and Oxidative Stress Markers in the Isolated Rat Heart: The Role of Different Gasotransmitters

Abstract

Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured: dp/dt max, dp/dt min, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2, O2 −, and H2O2 concentrations. The administration of DL-Hcy TLHC alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF, O2 −, H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increased dp/dt max but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease in dp/dt max, SLVP, HR, CF, and TBARS.

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

“…In study that examined the effects of various Hcy-related compounds (DL-Hcy, DL-Hcy thiolactone-hydrochloride (TLHC) and L-Hcy TLHC) the authors emphasized their harmful effects on cardiac function during acute administration in isolated rat heart (Zivkovic et al 2012). During acute application of DL-Hcy TLHC simultaneous inhibition of production of the gasotransmitters (NO, H 2 S and CO) additionally exacerbated the effects of DL-Hcy TLHC (Zivkovic et al 2013). The inhibition of CO production expressed most deleterious effects in comparison to deprivation of NO and H 2 S production.…”

Melatonin Regulates Oxidative Stress Initiated by Freund’s Complete Adjuvant

“…TBARS level serves as a direct proof of lipid peroxidation resulting in creation of malondialdehyde (27,28). The TBARS value becomes typically increased once an oxidative insult is uncovered by antioxidants (29,30). Owing to the experimental data, we can infer that Freund's complete adjuvant caused stressogenic effect; however, the effect was not extensive enough to causes uncovered oxidative insult (regarding to TBARS value) or depletion of antioxidants.…”

The effects of homocysteine and nitric oxide inhibitor, applied separately and simultaneously, on acetylcholinesterase activity in the rat heart tissue

“…Živković i autori navode da je dejstvo homocisteina na aktivnost AChE jedan od mogućih patofizioloških mehanizama za nastanak bradikardije i aritmije (22). Ova grupa autora takođe navodi da homocistein tiolakton dovodi do smanjenja srčane kontraktilnosti (23). Dobijeni rezultati govore u prilog činjenici da smanjena aktivnost AChE može da izazove smanjenje srčane kontraktilnosti i nastanak aritmija, verovatno smanjenom razgradnjom i povećanjem koncentracije parasimpatič-kog neurotransmitera acetilholina, koji ostvaruje poznate efekte na srce (negativno inotropno, hronotropno dromotropno i batmotropno dejstvo).…”

“…Živković i autori navode da kombinacija homocistein tiolaktona i Zn PPR IX dovodi do negativnog inotropnog i hronotropnog dejstva na izolovanom srcu pacova (23). U našim eksperimentima, kombinacija homocisteina i Zn PPR IX dovela je do povećane aktivnosti AChE u odnosu na kontrolnu grupu (povećanje je iznosilo 23%).…”