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A Calorimetric Investigation of the Effects of Acipimox on DPPC Model Membranes

Yıl 2023, Cilt: 10 Sayı: 3, 563 - 570, 23.07.2023
https://doi.org/10.30910/turkjans.1247158

Öz

Liposomes or model membranes are widely used basic systems which mimic biological membranes. In this study, the physical interaction between dipalmitoyl phosphatidylcholine (DPPC) and the lipid-lowering drug acipimox was investigated using Differential Scanning Calorimetry (DSC) technique depending on different acipimox concentrations and temperature. The changes in the phase transition temperature, phase transition enthalpy and phase transition curve half-height width of the model membranes were taken into account. According to the DSC results, with the addition of acipimox into pure DPPC model membranes, the main phase transition temperature curve, which is around 41 °C, shifted to slightly higher temperatures, while the pre-transition temperature curve, which is around 35 °C, did not disappear. Moreover, increasing acipimox concentrations caused a slight broadening of the DSC thermograms of the model membrane DPPC. Since it is very important to understand the pharmacological activity of drugs in biomembranes, the investigation of the interaction between lipid-lowering drug acipimox and lipids may contribute to the biological effects of acipimox at the molecular level.

Kaynakça

  • Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M., Nejati-Koshki, K. 2013. Liposome: classification, preparation, and applications. Nanoscale Research Letters, 22, 8 (1): 102.
  • Alakoskela, J-M. 2005. Interactions in Lipid-Water Interface Assessed by Fluorescence Spectroscopy, Ph.D. thesis, University of Helsinki, Finland.
  • Barayan, D., Vinaik, R., Auger, C., Knuth, C.M., Abdullahi, A., Jeschke, M.G. 2020. Inhibition of Lipolysis with Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration. Shock, 53 (2): 137-145.
  • Brasseur, G., Pillot, T., Lins, L., Vandekerckhove, J., Rosseneu M. 1997. Peptides in membranes: tipping the balance of membrane stability. Trends in Biochemical Sciences, 22: 167-171.
  • Cakmak Arslan, G. and Severcan, F. 2019. The effects of radioprotectant and potential antioxidant agent amifostine on the structure and dynamics of DPPC and DPPG liposomes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1861: 1240-1251.
  • Ceckler, T.L. and Cunningham, B.A. 1997. Transition State Thermodynamics of Lipid Bilayers Characterized by Differential Scanning Calorimetry. The Chemical Educator, 2 (6): 1-17.
  • Chen, W., Duša, F., Witos, J., Ruokonen, S-K., Wiedmer, S.K. 2018. Determination of the Main Phase Transition Temperature of Phospholipids by Nanoplasmonic Sensing. Scientific Reports, 8 (1).
  • Christie, A.W., McCormick, D.K.T., Emmison, N., Kraemer, F.B., Alberti, K.G.M.M., Yeaman, S. 1996. Mechanism of anti-lipolytic action of acipimox in isolated rat adipocytes. Diabetologia, 39: 45-53.
  • Ergun, S., Demir, P., Uzbay, T., Severcan, F. 2014. Agomelatine strongly interacts with zwitterionic DPPC and charged DPPG membranes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1838 (11): 2798-2806.
  • Ezer, N., Sahin, I., Kazanci, N. 2017. Alliin interacts with DMPC model membranes to modify the membrane dynamics: FTIR and DSC Studies. Vibrational Spectroscopy, 89: 1-8.
  • Frallicciardi, J., Frallicciardi, J., Melcr, J., Siginou, P., Marrink, S.J., Poolman, B. 2022. Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes. Nature Communications, 13: 1605.
  • Kaur, S., Auger, C., Jeschke, M.G. 2020. Adipose Tissue Metabolic Function and Dysfunction: Impact of Burn Injury. Frontiers in Cell and Developmental Biology, 8.
  • Koynova, R. and Tenchov, B. 2013. “Taken: Phase Transitions and Phase Behavior of Lipids. (ed) Roberts, G.C.K., Encyclopedia of Biophysics, Springer, Berlin, Heidelberg.
  • Kranenburg, M. and Smit, B. 2005. Phase Behavior of Model Lipid Bilayers. The Journal of Physical Chemistry B, 109 (14): 6553-6563.
  • Li, H., Zhao, T., Sun, Z. 2018. Analytical techniques and methods for study of drug-lipid membrane interactions. Reviews in Analytical Chemistry, 37 (1): 20170012.
  • Lombardo, D. and Kiselev, M.A. 2022. Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application. Pharmaceutics, 14: 543.
  • Lupachyk, S., Watcho, P., Hasanova, N., Julius, U., Obrosova, I.G. 2012. Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress. Free Radical Biology and Medicine, 52 (8): 1255-1263.
  • Minigh, J. 2007. Acipimox. “Taken: xPharm: The Comprehensive Pharmacology Reference. (ed) Enna, S.J., Bylund, D.B., Elsevier, 1-5.
  • Sahin, I., Bilge, D., Kazanci, N., Severcan, F. 2013. Concentration-dependent effect of melatonin on DSPC membrane. Journal of Molecular Structure, 1052: 183-188.
  • Saloranta, C, Taskinen, M.R., Widen, Härkönen, E.M., Melander, A., Groop. L. 1993. Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM. Diabetes, 42: 1559-1566.
  • Salvador, C., Entenmann, A., Salvador, R., Niederwanger, A., Crazzolara, R., Kropshofer, G. 2018. Combination therapy of omega-3 fatty acids and acipimox for children with hypertriglyceridemia and acute lymphoblastic leukemia. Journal of Clinical Lipidology, 12 (5): 1260-1266.
  • Sanghvi, R. and Yalkowsky, S.H. 2006. Estimation of heat capacity of boiling of organic compounds. Industrial & Engineering Chemistry Research, 45 (1): 451-453.
  • Sariisik, E., Koçak, M., Kucuk Baloglu, F., Severcan, F. 2019. Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1861: 810-818.
  • Severcan, F. and Dorohoi, D-O. 2008. FTIR studies of temperature influence on the DPPG model membrane. Journal of Molecular Structure, 887 (1-3): 117-121.
  • Severcan, F., Kazanci, N., Zorlu, F. 2000. Tamoxifen increases membrane fluidity at high concentrations. Bioscience Reports, 20: 177-184.
  • Severcan, F., Sahin, I., Kazanci, N. 2005. Melatonin strongly interacts with zwitterionic model membranes--evidence from Fourier transform infrared spectroscopy and differential scanning calorimetry. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1668 (2): 215-222.
  • Sirtori, C.R., Gianfranceschi, G., Sirtori, M., Bernini, F., Descovich, G., Montaguti, U., Fuccella, L.M., Musatti, L. 1981. Reduced triglyceridemia and increased high density lipoprotein cholesterol levels after treatment with acipimox, a new inhibitor of lipolysis. Atherosclerosis, 38: 267-271.
  • Stuyt, P. 1998. Tolerability and effects of high doses acipimox as additional lipid-lowering therapy in familial hypercholesterolemia. The Netherlands Journal of Medicine, 53 (5): 228-233.
  • Szoka Jr., F. and Papahadjopoulos, D. 1980. Comparative Properties and Methods of Preparation of Lipid Vesicles (Liposomes). Annual Review of Biophysics and Bioengineering, 9:467-508.
  • Taskinen, M.R. and Nikkilä, E.A. 1988. Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia. Atherosclerosis, 69: 249-255.
  • Toyran, N. and Severcan, F. 2002. Infrared spectroscopic studies on the dipalmitoyl phosphotidylcholine bilayer interactions with calcium phosphate: effect of vitamin D2. Spectroscopy, 16: 399-408.
  • Toyran, N. and Severcan, F. 2003. Competitive effect of Vitamin D2 and Ca2+ on phospholipid model membranes: a FTIR study. Chemistry and Physics of Lipids, 123: 165-176.
  • Turker, S., Wassall, S., Stillwell, W., Severcan, F. 2011. Convulsant agent pentylenetetrazol does not alter the structural and dynamical properties of dipalmitoylphosphatidylcholine model membranes. Journal of Pharmaceutical and Biomedical Analysis, 54: 379-386.
  • Vardarli, E., Bhattarai, N., Abdelrahman, D., El-Ayadi, A., Murton, A. 2022. Use of the Lipolysis Inhibitor Acipimox Fails to Modulate Chronic Muscle Protein Synthesis Rates or Attenuate the Loss of Muscle Mass in a Rodent Model of Severe Burns. The FASEB Journal, 36 (S1).
  • Vestergaard, E.T., Cichosz, S.L., Møller, N., Jørgensen, J.O.L, Fleischer, J. 2017. Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation. British Journal of Clinical Pharmacology, 83 (12): 2671–2677.
  • Vickers, M.H., Hofman, P.L., Gluckman, P.D., Lobie, P.E., Cutfield, W.S. 2006. Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat. American Journal of Physiology-Endocrinology and Metabolism, 291 (6): 1212-1219.
  • Watson, H. 2015. Biological membranes. Essays in Biochemistry, 59: 43-69.
  • Worm, D., Henriksen, J.E., Vaag, A., Thye-Rønn, P., Melander, A., Beck-Nielsen, H. 1994. Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period. The Journal of Clinical Endocrinology & Metabolism, 78: 717-721.
  • Wu, M. and Yalkowsky, S. 2009. Estimation of the molar heat capacity change on melting of organic compounds. Industrial & Engineering Chemistry Research, 48 (6): 3260-3260.
  • Yagofarov, M.I., Balakhontsev, I.S., Miroshnichenko, E.A., Solomonov, B.N. 2022. Estimation of sublimation enthalpies of aromatic compounds as a function of temperature. The Journal of Chemical Thermodynamics, 174: 106861.
  • Yagofarov, M.I., Nagrimanov, R.N., Solomonov, B.N. 2018. New aspects in the thermochemistry of solid-liquid phase transitions of organic non-electrolytes. Journal of Molecular Liquids, 256: 58-66.
  • Zhao, H. and Lappalainen, P.A. 2012. Simple guide to biochemical approaches for analyzing protein-lipid interactions. Molecular Biology of the Cell, 23 (15): 2823-30.

Asipimoksun DPPC Model Membranlar Üzerindeki Etkilerinin Kalorimetrik İncelenmesi

Yıl 2023, Cilt: 10 Sayı: 3, 563 - 570, 23.07.2023
https://doi.org/10.30910/turkjans.1247158

Öz

Model membranlar, biyolojik membranları taklit eden temel sistemler olarak yaygın şekilde kullanılmaktadır. Bu çalışmada, dipalmitoil fosfatidilkolin (DPPC) ile lipit düşürücü ilaç asipimoks arasındaki fiziksel etkileşim, farklı asipimoks konsantrasyonları ve sıcaklığa bağlı olarak Diferansiyel Tarama Kalorimetri (DSC) tekniği kullanılarak araştırıldı. DPPC içeren model membranların faz geçiş sıcaklığı, faz geçiş entalpisi ve faz geçiş eğrisi yarı yükseklik genişliğindeki değişimler değerlendirildi. DSC sonuçlarına göre saf DPPC model membranlara asipimoks ilavesi ile 41 °C civarındaki ana faz geçiş sıcaklık eğrisi biraz daha yüksek sıcaklıklara kayarken, 35 °C civarındaki geçiş öncesi sıcaklık eğrisi kaybolmadı. Ayrıca, artan asipimoks konsantrasyonları, model membran DPPC'nin DSC termogramlarında hafif bir genişlemeye neden oldu. İlaçların biyomembranlardaki farmakolojik aktivitelerinin anlaşılması onların hücre içi aktivileri açısından çok önemli olduğu için, lipit düşürücü ilaç asipimoks ile lipitler arasındaki etkileşimin araştırılması, asipimoksun moleküler düzeydeki biyolojik etkilerine katkı sağlayabilir.

Kaynakça

  • Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M., Nejati-Koshki, K. 2013. Liposome: classification, preparation, and applications. Nanoscale Research Letters, 22, 8 (1): 102.
  • Alakoskela, J-M. 2005. Interactions in Lipid-Water Interface Assessed by Fluorescence Spectroscopy, Ph.D. thesis, University of Helsinki, Finland.
  • Barayan, D., Vinaik, R., Auger, C., Knuth, C.M., Abdullahi, A., Jeschke, M.G. 2020. Inhibition of Lipolysis with Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration. Shock, 53 (2): 137-145.
  • Brasseur, G., Pillot, T., Lins, L., Vandekerckhove, J., Rosseneu M. 1997. Peptides in membranes: tipping the balance of membrane stability. Trends in Biochemical Sciences, 22: 167-171.
  • Cakmak Arslan, G. and Severcan, F. 2019. The effects of radioprotectant and potential antioxidant agent amifostine on the structure and dynamics of DPPC and DPPG liposomes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1861: 1240-1251.
  • Ceckler, T.L. and Cunningham, B.A. 1997. Transition State Thermodynamics of Lipid Bilayers Characterized by Differential Scanning Calorimetry. The Chemical Educator, 2 (6): 1-17.
  • Chen, W., Duša, F., Witos, J., Ruokonen, S-K., Wiedmer, S.K. 2018. Determination of the Main Phase Transition Temperature of Phospholipids by Nanoplasmonic Sensing. Scientific Reports, 8 (1).
  • Christie, A.W., McCormick, D.K.T., Emmison, N., Kraemer, F.B., Alberti, K.G.M.M., Yeaman, S. 1996. Mechanism of anti-lipolytic action of acipimox in isolated rat adipocytes. Diabetologia, 39: 45-53.
  • Ergun, S., Demir, P., Uzbay, T., Severcan, F. 2014. Agomelatine strongly interacts with zwitterionic DPPC and charged DPPG membranes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1838 (11): 2798-2806.
  • Ezer, N., Sahin, I., Kazanci, N. 2017. Alliin interacts with DMPC model membranes to modify the membrane dynamics: FTIR and DSC Studies. Vibrational Spectroscopy, 89: 1-8.
  • Frallicciardi, J., Frallicciardi, J., Melcr, J., Siginou, P., Marrink, S.J., Poolman, B. 2022. Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes. Nature Communications, 13: 1605.
  • Kaur, S., Auger, C., Jeschke, M.G. 2020. Adipose Tissue Metabolic Function and Dysfunction: Impact of Burn Injury. Frontiers in Cell and Developmental Biology, 8.
  • Koynova, R. and Tenchov, B. 2013. “Taken: Phase Transitions and Phase Behavior of Lipids. (ed) Roberts, G.C.K., Encyclopedia of Biophysics, Springer, Berlin, Heidelberg.
  • Kranenburg, M. and Smit, B. 2005. Phase Behavior of Model Lipid Bilayers. The Journal of Physical Chemistry B, 109 (14): 6553-6563.
  • Li, H., Zhao, T., Sun, Z. 2018. Analytical techniques and methods for study of drug-lipid membrane interactions. Reviews in Analytical Chemistry, 37 (1): 20170012.
  • Lombardo, D. and Kiselev, M.A. 2022. Methods of Liposomes Preparation: Formation and Control Factors of Versatile Nanocarriers for Biomedical and Nanomedicine Application. Pharmaceutics, 14: 543.
  • Lupachyk, S., Watcho, P., Hasanova, N., Julius, U., Obrosova, I.G. 2012. Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: role for oxidative–nitrosative stress. Free Radical Biology and Medicine, 52 (8): 1255-1263.
  • Minigh, J. 2007. Acipimox. “Taken: xPharm: The Comprehensive Pharmacology Reference. (ed) Enna, S.J., Bylund, D.B., Elsevier, 1-5.
  • Sahin, I., Bilge, D., Kazanci, N., Severcan, F. 2013. Concentration-dependent effect of melatonin on DSPC membrane. Journal of Molecular Structure, 1052: 183-188.
  • Saloranta, C, Taskinen, M.R., Widen, Härkönen, E.M., Melander, A., Groop. L. 1993. Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM. Diabetes, 42: 1559-1566.
  • Salvador, C., Entenmann, A., Salvador, R., Niederwanger, A., Crazzolara, R., Kropshofer, G. 2018. Combination therapy of omega-3 fatty acids and acipimox for children with hypertriglyceridemia and acute lymphoblastic leukemia. Journal of Clinical Lipidology, 12 (5): 1260-1266.
  • Sanghvi, R. and Yalkowsky, S.H. 2006. Estimation of heat capacity of boiling of organic compounds. Industrial & Engineering Chemistry Research, 45 (1): 451-453.
  • Sariisik, E., Koçak, M., Kucuk Baloglu, F., Severcan, F. 2019. Interaction of the cholesterol reducing agent simvastatin with zwitterionic DPPC and charged DPPG phospholipid membranes. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1861: 810-818.
  • Severcan, F. and Dorohoi, D-O. 2008. FTIR studies of temperature influence on the DPPG model membrane. Journal of Molecular Structure, 887 (1-3): 117-121.
  • Severcan, F., Kazanci, N., Zorlu, F. 2000. Tamoxifen increases membrane fluidity at high concentrations. Bioscience Reports, 20: 177-184.
  • Severcan, F., Sahin, I., Kazanci, N. 2005. Melatonin strongly interacts with zwitterionic model membranes--evidence from Fourier transform infrared spectroscopy and differential scanning calorimetry. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1668 (2): 215-222.
  • Sirtori, C.R., Gianfranceschi, G., Sirtori, M., Bernini, F., Descovich, G., Montaguti, U., Fuccella, L.M., Musatti, L. 1981. Reduced triglyceridemia and increased high density lipoprotein cholesterol levels after treatment with acipimox, a new inhibitor of lipolysis. Atherosclerosis, 38: 267-271.
  • Stuyt, P. 1998. Tolerability and effects of high doses acipimox as additional lipid-lowering therapy in familial hypercholesterolemia. The Netherlands Journal of Medicine, 53 (5): 228-233.
  • Szoka Jr., F. and Papahadjopoulos, D. 1980. Comparative Properties and Methods of Preparation of Lipid Vesicles (Liposomes). Annual Review of Biophysics and Bioengineering, 9:467-508.
  • Taskinen, M.R. and Nikkilä, E.A. 1988. Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia. Atherosclerosis, 69: 249-255.
  • Toyran, N. and Severcan, F. 2002. Infrared spectroscopic studies on the dipalmitoyl phosphotidylcholine bilayer interactions with calcium phosphate: effect of vitamin D2. Spectroscopy, 16: 399-408.
  • Toyran, N. and Severcan, F. 2003. Competitive effect of Vitamin D2 and Ca2+ on phospholipid model membranes: a FTIR study. Chemistry and Physics of Lipids, 123: 165-176.
  • Turker, S., Wassall, S., Stillwell, W., Severcan, F. 2011. Convulsant agent pentylenetetrazol does not alter the structural and dynamical properties of dipalmitoylphosphatidylcholine model membranes. Journal of Pharmaceutical and Biomedical Analysis, 54: 379-386.
  • Vardarli, E., Bhattarai, N., Abdelrahman, D., El-Ayadi, A., Murton, A. 2022. Use of the Lipolysis Inhibitor Acipimox Fails to Modulate Chronic Muscle Protein Synthesis Rates or Attenuate the Loss of Muscle Mass in a Rodent Model of Severe Burns. The FASEB Journal, 36 (S1).
  • Vestergaard, E.T., Cichosz, S.L., Møller, N., Jørgensen, J.O.L, Fleischer, J. 2017. Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation. British Journal of Clinical Pharmacology, 83 (12): 2671–2677.
  • Vickers, M.H., Hofman, P.L., Gluckman, P.D., Lobie, P.E., Cutfield, W.S. 2006. Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat. American Journal of Physiology-Endocrinology and Metabolism, 291 (6): 1212-1219.
  • Watson, H. 2015. Biological membranes. Essays in Biochemistry, 59: 43-69.
  • Worm, D., Henriksen, J.E., Vaag, A., Thye-Rønn, P., Melander, A., Beck-Nielsen, H. 1994. Pronounced blood glucose-lowering effect of the antilipolytic drug acipimox in noninsulin-dependent diabetes mellitus patients during a 3-day intensified treatment period. The Journal of Clinical Endocrinology & Metabolism, 78: 717-721.
  • Wu, M. and Yalkowsky, S. 2009. Estimation of the molar heat capacity change on melting of organic compounds. Industrial & Engineering Chemistry Research, 48 (6): 3260-3260.
  • Yagofarov, M.I., Balakhontsev, I.S., Miroshnichenko, E.A., Solomonov, B.N. 2022. Estimation of sublimation enthalpies of aromatic compounds as a function of temperature. The Journal of Chemical Thermodynamics, 174: 106861.
  • Yagofarov, M.I., Nagrimanov, R.N., Solomonov, B.N. 2018. New aspects in the thermochemistry of solid-liquid phase transitions of organic non-electrolytes. Journal of Molecular Liquids, 256: 58-66.
  • Zhao, H. and Lappalainen, P.A. 2012. Simple guide to biochemical approaches for analyzing protein-lipid interactions. Molecular Biology of the Cell, 23 (15): 2823-30.
Toplam 42 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Bitki Hücresi ve Moleküler Biyoloji
Bölüm Araştırma Makalesi
Yazarlar

Nazlı Ezer Özer 0000-0002-2313-4218

İpek Şahin 0000-0002-2233-9852

Erken Görünüm Tarihi 24 Temmuz 2023
Yayımlanma Tarihi 23 Temmuz 2023
Gönderilme Tarihi 3 Şubat 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 10 Sayı: 3

Kaynak Göster

APA Ezer Özer, N., & Şahin, İ. (2023). A Calorimetric Investigation of the Effects of Acipimox on DPPC Model Membranes. Türk Tarım Ve Doğa Bilimleri Dergisi, 10(3), 563-570. https://doi.org/10.30910/turkjans.1247158