EFFECTS OF [(DIMETHYLPHOSPHINYLMETHYL)AMINO](CHLOROPHENYL)-METHYLPHOSPHONIC ACID AND N-(PHOSPHONOMETHYL) GLYCINE ON ATPase ACTIVITY OF RAT LIVER MITOCHONDRIA
MILENA SHKODROVA1*, MARIELA CHICHOVA1,VESELIN DOBRINOV1, DILYANA DONCHEVA-STOIMENOVA1, DIMITAR GANCHEV1, YULIAN ZAGRANIARSKY2, TSVETANKA CHOLAKOVA2, SABI VARBANOV3
1 Department of Animal and Human Physiology, Faculty of Biology, University of Sofia, Dragan Tzankov Blvd. 8, 1164 Sofia, Bulgaria
2 Department of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia, James Bourchier Blvd. 1, 1164 Sofia, Bulgaria
3 Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Akad. Georgi Bonchev Str. 9, 1113 Sofia, Bulgaria
*Corresponding author: e-mail: milshk@abv.bg
Keywords: aminophosphonic acids, dimethylphosphinyl-substituted phosphonates, glyphosate, mitochondria, mitochondrial ATPase
Abstract: During the last decades, aminophosphonic acids and theirs derivatives are widely used as antimicrobial, antiviral, antitumor agents, herbicides, plant growth regulators. However, data were presented that the aminophosphonates applied as herbicides in agriculture exhibit toxic effects on animal and human organisms. A detailed study of the commercial aminophosphonates effects on cells and cell organelles would provide a better insight into the mechanisms of their biological action.
The purpose of the current work was to study the effects of two aminophosphonates –a newly synthesized [(Dimethylphosphinylmethyl)amino](chlorophenyl)-methylphosphonic acid (DMCPPA) and a commercially used N-(phosphonomethyl) glycine (glyphosate), on ATPase activity of rat liver mitochondria. Two different mitochondrial preparations were used: intact mitochondria and mitochondria uncoupled by freezing/thawing.
DMCPPA did not influence ATPase activity of intact mitochondria and insignificantly increased the activity of 2,4-dinitrophenol (DNP)-uncoupled mitochondria. This suggests that DMCPPA does not possess an uncoupling effect on intact liver mitochondria and is not able to pass the inner mitochondrial membrane. DMCPPA insignificantly reduced ATPase activities of freeze/thawed mitochondria. The herbicide Cosmic® with an active ingredient glyphosate stimulated ATP hydrolysis in intact mitochondria and ATPase activity of DNP-uncoupled mitochondria, which suggests that the compound possesses uncoupling effect on intact mitochondria and is able to pass the inner mitochondrial membrane. Cosmic® increased ATPase activity of freeze/thawed mitochondria.
The differences in the effects of the newly synthesized DMCPPA and herbicide Cosmic® may be due to supplements in the composition of Cosmic® (anionic surfactant) and/or to different chemical structures of the glyphosate and DMCPPA, which determine different biological activity.
Our results provide an insight into the mechanisms of the biological action of the aminophosphonates on the living systems, in particular on mitochondria.