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Uzelac, Jovana Jakovljević; Stanić, Marina; Krstić, Danijela; Čolović, Mirjana; Djurić, Dragan
Molecular and cellular biochemistry, 07/2018, Letnik: 444, Številka: 1-2Journal Article
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.
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