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

• Published in: Molecular and cellular biochemistry 2018-07, Vol.444 (1-2), p.143-148
• Main Authors: Uzelac, Jovana Jakovljević, Stanić, Marina, Krstić, Danijela, Čolović, Mirjana, Djurić, Dragan
• Format: Article
• Language: English
• Subjects: Animal tissues; Animals; Arginine; Biochemistry; Biomedical and Life Sciences; Cardiology; Cardiotoxicity; Gasotransmitters - pharmacology; Heart; Homocysteine; Homocysteine - analogs & derivatives; Homocysteine - pharmacology; Hydrogen sulfide; Inhibitors; L-Homocysteine; Life Sciences; Male; Medical Biochemistry; Myocardium - metabolism; Neurotransmitters; NG-Nitroarginine methyl ester; Oncology; Oxygen; Oxygen consumption; Oxygen Consumption - drug effects; Protoporphyrin; Protoporphyrin IX; Rats; Rats, Wistar; Rodents; Studies; Synthesis; Thiolactone; Tissues; Zinc protoporphyrin IX
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-017-3238-z

The objective of this study was to investigate in vitro effects of 10 µM 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, H 2 S 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 ω -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 µM), 5.32 ± 1.23% for dl -PAG (10 µM), and 5.56 ± 1.39% for ZnPPR IX (10 µM). Simultaneous effect of l -NAME (30 µM) or ZnPPR IX (10 µM) with dl -Hcy TLHC (10 µM) caused a larger decrease of oxygen consumption compared to each of the substances individually. However, when dl -PAG (10 µM) was applied together with dl -Hcy TLHC (10 µM), 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.