Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
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Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 3, May-June, p. 377–380

Publication type: original article

Language: English

Effect of Ketoprofen on Lactic Dehydrogenase from Human Platelets

Muhammad Tahir Razi1,A,E, Ibrahim Javed1,C,D, Muhammad Zabta Choudry2,F, Muhammad Tariq Khan1,B, Noreen Mukhtar1,B

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan

2 Multan Medical & dental college, Multan, Pakistan

Abstract

Background. In different clinical investigations of thrombocytopenia, ketoprofen was found to be the associated cause. Ketoprofen alone or in combination with other therapeutic regimens leads to a decrease in platelet count. Thrombocytopenia due to ketoprofen use can be a threatening condition to the patients who require uncompromised platelet function.
Objectives. In order to establish a mechanism for thrombocytopenia associated with ketoprofen use, the enzyme inhibition effects of ketoprofen on lactic dehydrogenase (LdH) were investigated in this study. LdH is essentially involved in platelet energy production.
Material and Methods. LdH isolated from human platelets was subjected to different concentrations of ketoprofen (250, 500, 750, 1000 and 1500 µg/mL) and pyruvate as a substrate (45, 60 and 90 µM/mL) to gain insight into the enzyme inhibition effects for forward reaction. Oxidation of nicotinamide adenine dinucleotide (NadH) was measured at 340 nm to evaluate enzyme activity. enzyme inhibition kinetics were studied via Lineweaver burk plot.
Results. Ketoprofen was found to be a competitive inhibitor of LdH in human platelets. 89% of enzyme activity was inhibited by a 1500 µg/mL concentration of the drug and the enzyme inhibition constant was 882 µg/mL.
Conclusion. The possible main cause of thrombocytopenia due to ketoprofen use is LdH inhibition in platelets, which are essential for platelet energy metabolism. So patients who require uncompromised platelet function and are receiving ketoprofen in their prescription should be monitored for platelet count and blood clotting.

Key words

ketoprofen, thrombocytopenia, lactic dehydrogenase, enzyme inhibition, pyruvate, kinetics.

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