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Modulation of Diverse Procoagulant Venom Activities by Combinations of Platinoid Compounds.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Apr 28; Vol. 22 (9). Date of Electronic Publication: 2021 Apr 28. - Publication Year :
- 2021
-
Abstract
- Procoagulant snake venoms have been inhibited by the ruthenium containing compounds CORM-2 and RuCl <subscript>3</subscript> separately, presumably by interacting with critical histidine or other sulfur-containing amino acids on key venom enzymes. However, combinations of these and other platinoid containing compounds could potentially increase, decrease or not affect the procoagulant enzyme function of venom. Thus, the purpose of this investigation was to determine if formulations of platinoid compounds could inhibit venom procoagulant activity and if the formulated compounds interacted to enhance inhibition. Using a human plasma coagulation kinetic model to assess venom activity, six diverse venoms were exposed to various combinations and concentrations of CORM-2, CORM-3, RuCl <subscript>3</subscript> and carboplatin (a platinum containing compound), with changes in venom activity determined with thrombelastography. The combinations of CORM-2 or CORM-3 with RuCl <subscript>3</subscript> were found to enhance inhibition significantly, but not in all venoms nor to the same extent. In sharp contrast, carboplatin-antagonized CORM-2 mediated the inhibition of venom activity. These preliminary results support the concept that platinoid compounds may inhibit venom enzymatic activity at the same or different molecular sites and may antagonize inhibition at the same or different sites. Further investigation is warranted to determine if platinoid formulations may serve as potential antivenoms.
- Subjects :
- Carboplatin pharmacology
Carboplatin therapeutic use
Drug Evaluation, Preclinical
Drug Therapy, Combination
Humans
Organometallic Compounds pharmacology
Ruthenium Compounds pharmacology
Snake Venoms pharmacology
Thrombelastography
Blood Coagulation drug effects
Organometallic Compounds therapeutic use
Ruthenium Compounds therapeutic use
Snake Bites drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33924780
- Full Text :
- https://doi.org/10.3390/ijms22094612