Effects of homocysteine and its related compounds on oxygen consumption of the rat heart tissue homogenate: the role of different gasotransmitters

Abstract

The objective of this study was to investigate in vitro effects of 10 A mu M dl-homocysteine (dl-Hcy), dl-homocysteine thiolactone-hydrochloride (dl-Hcy TLHC), and l-homocysteine thiolactone-hydrochloride (l-Hcy TLHC) on the oxygen consumption of rat heart tissue homogenate, as well as the involvement of the gasotransmitters NO, H2S and CO in the effects of the most toxic homocysteine compound, dl-Hcy TLHC. The possible contribution of the gasotransmitters in these effects was estimated by using the appropriate inhibitors of their synthesis (N (omega)-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (dl-PAG), and zinc protoporphyrin IX (ZnPPR IX), respectively). The oxygen consumption of rat heart tissue homogenate was measured by Clark/type oxygen electrode in the absence and presence of the investigated compounds. All three homocysteine-based compounds caused a similar decrease in the oxygen consumption rate compared to control: 15.19 +/- 4.01%, 12.42 +/- 1.01%, and 16.43 +/- 4.52% for dl-Hcy, dl-Hcy TLHC, or l-Hcy TLHC, respectively. All applied inhibitors of gasotransmitter synthesis also decreased the oxygen consumption rate of tissue homogenate related to control: 13.53 +/- 1.35% for l-NAME (30 A mu M), 5.32 +/- 1.23% for dl-PAG (10 A mu M), and 5.56 +/- 1.39% for ZnPPR IX (10 A mu M). Simultaneous effect of l-NAME (30 A mu M) or ZnPPR IX (10 A mu M) with dl-Hcy TLHC (10 A mu M) caused a larger decrease of oxygen consumption compared to each of the substances individually. However, when dl-PAG (10 A mu M) was applied together with dl-Hcy TLHC (10 A mu M), it attenuated the effect of dl-Hcy TLHC from 12.42 +/- 1.01 to 9.22 +/- 1.58%. In conclusion, cardiotoxicity induced by Hcy-related compounds, which was shown in our previous research, could result from the inhibition of the oxygen consumption, and might be mediated by the certain gasotransmitters.