J Thromb Thrombolysis DOI 10.1007/s11239-015-1211-9
LETTER TO THE EDITOR
Does 10-dehydrogingerdione affect serum albumin and free fatty acid levels as it does on serum ischemia-modified albumin? Varikasuvu Seshadri Reddy1 • Kalla Chandra Mouli2 • Y Mohan Reddy3
Ó Springer Science+Business Media New York 2015
We read with great interest the recent report by El-Seweidy et al. [1]. This interesting study has shown that 10-dehydrogingerdione (DHGD) improved coagulation-fibrinolysis homeostasis during dyslipidemia by improving endothelial function and serum ischemia-modified albumin (IMA) levels. However, we have a few interesting points unearthed during the reading and reviewing of literature. Firstly, IMA determination by colorimetric assays is susceptible to interference from a low or high HSA level, serum proteins and lipidemia [2]. Therefore, there is a stressing need for interference-free determination of IMA as a biomarker. Of great importance, there have been very recent methodological advancements in IMA assays for more accuracy [3, 4]. Although most of the studies associating low albumin to thromboembolism (TE) were performed in renal disease where renal loss of albumin and anti-thrombotic proteins occur, low serum albumin, being an acute phase reactant, may reflect inflammation, leading to TE [5, 6]. Recent evidence also shows that inflammation assessed by higher hsCRP and diminished albumin is associated with elevated TE risk [7]. Considering this previous evidence and authors own previous research [8] showing beneficial effects of DHGD in normalizing hsCRP and inflammation, it would
& Varikasuvu Seshadri Reddy [email protected] 1
Faculty of Medicine, Department of Biochemistry, BPS Govt. Medical College, Khanpur kalan, Sonepat, Haryana 131305, India
2
Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh 524001, India
3
Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502, India
have been importantly interesting to study the effect of DHGD on serum albumin levels. The need for this is furthermore supported by experimental evidence showing significant improvements of total protein and albumin levels upon ginger treatment. This increase in serum albumin may substantially contribute to increased antioxidant property of albumin in consistent with alleviated oxidative stress [9, 10]. Though the exact mechanisms are completely not clear, albumin plays a part in maintaining microvascular integrity. Albumin seems to affect blood coagulation and its anticoagulant effect is probably antithrombotic in nature by inhibiting platelet aggregation. Interestingly, it has been reported a decrease in the plasma concentrations of albumin while the plasma free-fatty acid (FFA) level increase in thrombosis. An increase in the plasma FFA/albumin ratio has been shown to increase fibrinogen synthesis, which is normalized upon restoring FFA/albumin ratio to normal [11]. Furthermore, albumin and FFAs respectively inhibit and activate platelet aggregation affecting thrombosis [11, 12]. Moreover, albumin serves as an obligatory co-factor that accepts FFAs released during the corrective clearing of alimentary lipemia. It is therefore to speculate that any condition leading to increased FFAs and/or decreased albumin concentrations would contribute to thrombosis. The link between low albumin and hyperfibrinogenemia has been reported in an animal model, triggering thrombotic tendency and atherosclerotic risk [13]. Hence, in our opinion, the authors could have considered studying of FFA/albumin ratio or it may warrant a strong consideration in further studying whether DHGD affects serum albumin and FFA level. Our views can be further strengthened when put in the context of IMA values. The authors have shown a significant increase in plasma levels of IMA and fibrinogen
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with a strong positive correlation between them. Based on these observations, and the known fact that plasma FFAs are bound to and transported by albumin, we hypothesize that albumin modifications (evidenced through the increased IMA formation) would have resulted in an impaired binding to FFAs, their subsequent elevation and thus high fibrinogen levels and thrombosis. On the other hand, dyslipidemic group could have exhibited a decrease in serum albumin level, thereby decreasing FFA-albumin binding resulting increased FFAs preceding increased thrombosis risk. Interestingly, FFAs allosterically inhibit cobalt binding to albumin [14] and may result in high IMA values. Finally, In addition to its known interference to IMA estimation, correction of IMA results for serum albumin concentrations is more important in view of a better performance of IMA: albumin ratio than IMA alone in studying TE risk [15].
References 1. El-Seweidy MM, Mel-S Asker, Eldahmy SI et al (2015) Haemostatic risk factors in dyslipidemic rabbits: role of 10-dehydrogingerdione as a new hypolipemic agent. J Thromb Thrombolysis 39:196–202 2. Kotani K, Caccavello R, Sakane N et al (2011) Influence of ezetimibe monotherapy on ischemia-modified albumin levels in hypercholesterolemic patients. Pharmacol Rep 63:1248–1251 3. Luo Y, Wang C, Jiang T et al (2014) Interference-free determination of ischemia-modified albumin using quantum dot coupled X-ray fluorescence spectroscopy. Biosens Bioelectron 51:136–142
123
4. Lee E, Eom JE, Jeon KH et al (2014) Evaluation of albumin structural modifications through cobalt-albumin binding (CAB) assay. J Pharm Biomed Anal 91:17–23 5. Fox EA, Kahn SR (2005) The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 94:362–365 6. Folsom AR, Lutsey PL, Heckbert SR et al (2010) Serum albumin and risk of venous thromboembolism. Thromb Haemost 104:100–104 7. Olson NC, Cushman M, Lutsey PL et al (2014) Inflammation markers and incident venous thromboembolism: the REasons for geographic and racial differences in stroke (REGARDS) cohort. J Thromb Haemost 12:1993–2001 8. Elseweidy MM, Abdallah FR, Younis NN et al (2013) 10-Dehydrogingerdione raises HDLcholesterol through a CETP inhibition and wards off oxidation and inflammation in dyslipidemic rabbits. Atherosclerosis 231:334–340 9. Abdel-Azeem AS, Hegazy AM, Ibrahim KS et al (2013) Hepatoprotective, antioxidant, and ameliorative effects of ginger (Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats. J Diet Suppl 10:195–209 10. Al-Katib SM, Al-Khashab EM, Kalo MS et al (2009) The antioxidant effects of flavonoids and non flavonoid part extracted from ginger (Zingiber officinale) oots. Jou Raf Sci 20:18–31 11. Pilgeram L (2010) Control of fibrinogen biosynthesis: role of the FFA/Albumin Ratio. Cardiovasc Eng 10:78–83 12. Dhindsa S, Ghanim H, Dandona P et al (2015) Nonesterified Fatty acids, albumin, and platelet aggregation. Diabetes 64:703–705 13. Pickart LR, Thaler MM (1976) Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Am J Physiol 230:996–1002 14. Lu J, Stewart AJ, Sadler PJ et al (2012) Allosteric inhibition of cobalt binding to albumin by fatty acids: implications for the detection of myocardial ischemia. J Med Chem 55:4425–4430 15. Hogg K, Hinchliffe E, Halsam S et al (2012) Is ischaemiamodified albumin a test for venous thromboembolism? Emerg Med J 29:455–459
LETTER TO THE EDITOR
Does 10-dehydrogingerdione affect serum albumin and free fatty acid levels as it does on serum ischemia-modified albumin? Varikasuvu Seshadri Reddy1 • Kalla Chandra Mouli2 • Y Mohan Reddy3
Ó Springer Science+Business Media New York 2015
We read with great interest the recent report by El-Seweidy et al. [1]. This interesting study has shown that 10-dehydrogingerdione (DHGD) improved coagulation-fibrinolysis homeostasis during dyslipidemia by improving endothelial function and serum ischemia-modified albumin (IMA) levels. However, we have a few interesting points unearthed during the reading and reviewing of literature. Firstly, IMA determination by colorimetric assays is susceptible to interference from a low or high HSA level, serum proteins and lipidemia [2]. Therefore, there is a stressing need for interference-free determination of IMA as a biomarker. Of great importance, there have been very recent methodological advancements in IMA assays for more accuracy [3, 4]. Although most of the studies associating low albumin to thromboembolism (TE) were performed in renal disease where renal loss of albumin and anti-thrombotic proteins occur, low serum albumin, being an acute phase reactant, may reflect inflammation, leading to TE [5, 6]. Recent evidence also shows that inflammation assessed by higher hsCRP and diminished albumin is associated with elevated TE risk [7]. Considering this previous evidence and authors own previous research [8] showing beneficial effects of DHGD in normalizing hsCRP and inflammation, it would
& Varikasuvu Seshadri Reddy [email protected] 1
Faculty of Medicine, Department of Biochemistry, BPS Govt. Medical College, Khanpur kalan, Sonepat, Haryana 131305, India
2
Department of Biotechnology, Vikrama Simhapuri University, Nellore, Andhra Pradesh 524001, India
3
Department of Biotechnology, Sri Venkateswara University, Tirupati, Andhra Pradesh 517502, India
have been importantly interesting to study the effect of DHGD on serum albumin levels. The need for this is furthermore supported by experimental evidence showing significant improvements of total protein and albumin levels upon ginger treatment. This increase in serum albumin may substantially contribute to increased antioxidant property of albumin in consistent with alleviated oxidative stress [9, 10]. Though the exact mechanisms are completely not clear, albumin plays a part in maintaining microvascular integrity. Albumin seems to affect blood coagulation and its anticoagulant effect is probably antithrombotic in nature by inhibiting platelet aggregation. Interestingly, it has been reported a decrease in the plasma concentrations of albumin while the plasma free-fatty acid (FFA) level increase in thrombosis. An increase in the plasma FFA/albumin ratio has been shown to increase fibrinogen synthesis, which is normalized upon restoring FFA/albumin ratio to normal [11]. Furthermore, albumin and FFAs respectively inhibit and activate platelet aggregation affecting thrombosis [11, 12]. Moreover, albumin serves as an obligatory co-factor that accepts FFAs released during the corrective clearing of alimentary lipemia. It is therefore to speculate that any condition leading to increased FFAs and/or decreased albumin concentrations would contribute to thrombosis. The link between low albumin and hyperfibrinogenemia has been reported in an animal model, triggering thrombotic tendency and atherosclerotic risk [13]. Hence, in our opinion, the authors could have considered studying of FFA/albumin ratio or it may warrant a strong consideration in further studying whether DHGD affects serum albumin and FFA level. Our views can be further strengthened when put in the context of IMA values. The authors have shown a significant increase in plasma levels of IMA and fibrinogen
123
V. S. Reddy et al.
with a strong positive correlation between them. Based on these observations, and the known fact that plasma FFAs are bound to and transported by albumin, we hypothesize that albumin modifications (evidenced through the increased IMA formation) would have resulted in an impaired binding to FFAs, their subsequent elevation and thus high fibrinogen levels and thrombosis. On the other hand, dyslipidemic group could have exhibited a decrease in serum albumin level, thereby decreasing FFA-albumin binding resulting increased FFAs preceding increased thrombosis risk. Interestingly, FFAs allosterically inhibit cobalt binding to albumin [14] and may result in high IMA values. Finally, In addition to its known interference to IMA estimation, correction of IMA results for serum albumin concentrations is more important in view of a better performance of IMA: albumin ratio than IMA alone in studying TE risk [15].
References 1. El-Seweidy MM, Mel-S Asker, Eldahmy SI et al (2015) Haemostatic risk factors in dyslipidemic rabbits: role of 10-dehydrogingerdione as a new hypolipemic agent. J Thromb Thrombolysis 39:196–202 2. Kotani K, Caccavello R, Sakane N et al (2011) Influence of ezetimibe monotherapy on ischemia-modified albumin levels in hypercholesterolemic patients. Pharmacol Rep 63:1248–1251 3. Luo Y, Wang C, Jiang T et al (2014) Interference-free determination of ischemia-modified albumin using quantum dot coupled X-ray fluorescence spectroscopy. Biosens Bioelectron 51:136–142
123
4. Lee E, Eom JE, Jeon KH et al (2014) Evaluation of albumin structural modifications through cobalt-albumin binding (CAB) assay. J Pharm Biomed Anal 91:17–23 5. Fox EA, Kahn SR (2005) The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 94:362–365 6. Folsom AR, Lutsey PL, Heckbert SR et al (2010) Serum albumin and risk of venous thromboembolism. Thromb Haemost 104:100–104 7. Olson NC, Cushman M, Lutsey PL et al (2014) Inflammation markers and incident venous thromboembolism: the REasons for geographic and racial differences in stroke (REGARDS) cohort. J Thromb Haemost 12:1993–2001 8. Elseweidy MM, Abdallah FR, Younis NN et al (2013) 10-Dehydrogingerdione raises HDLcholesterol through a CETP inhibition and wards off oxidation and inflammation in dyslipidemic rabbits. Atherosclerosis 231:334–340 9. Abdel-Azeem AS, Hegazy AM, Ibrahim KS et al (2013) Hepatoprotective, antioxidant, and ameliorative effects of ginger (Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats. J Diet Suppl 10:195–209 10. Al-Katib SM, Al-Khashab EM, Kalo MS et al (2009) The antioxidant effects of flavonoids and non flavonoid part extracted from ginger (Zingiber officinale) oots. Jou Raf Sci 20:18–31 11. Pilgeram L (2010) Control of fibrinogen biosynthesis: role of the FFA/Albumin Ratio. Cardiovasc Eng 10:78–83 12. Dhindsa S, Ghanim H, Dandona P et al (2015) Nonesterified Fatty acids, albumin, and platelet aggregation. Diabetes 64:703–705 13. Pickart LR, Thaler MM (1976) Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Am J Physiol 230:996–1002 14. Lu J, Stewart AJ, Sadler PJ et al (2012) Allosteric inhibition of cobalt binding to albumin by fatty acids: implications for the detection of myocardial ischemia. J Med Chem 55:4425–4430 15. Hogg K, Hinchliffe E, Halsam S et al (2012) Is ischaemiamodified albumin a test for venous thromboembolism? Emerg Med J 29:455–459
