Pharmacodynamic and pharmacokinetic studies on novel vanadyl chrysin complex

January 14, 2013

Pharmacodynamic and pharmacokinetic studies on novel vanadyl chrysin complex

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Title:	Pharmacodynamic and pharmacokinetic studies on novel vanadyl chrysin complex
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Article_Title:	Pharmacodynamic and pharmacokinetic studies on novel vanadyl chrysin complex
Authors:	Bruno Stefan Velescu, Valentina Uivaroşi, Valentina Anuţa, Anca Buzescu, Simona Negreş
Affiliation:	Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Department of Inorganic Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Department of Physical chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Abstract:	A novel complex with general formula VO(chrysin) ·4H O was studied in order to evaluate its’ 2 2 pharmacodynamic action, and its’ pharmacokinetic properties. The hypoglycemic activity of the complex was evaluated in an alloxan diabetic rat model, and compared to chrysin and vanadyl sulphate. The pharmacokinetic properties were studied following a single dose administration, in compartmental and non-compartmental analyses. The complex has a low toxicity and a low hypoglycemic effect (p>0.05) correlated with the pharmacokinetic parameters (volume of distribution, half time and micro-constants).
Keywords:	vanadyl chrysin complex, pharmacodynamic action, pharmacokinetic properties, hypoglycemic activity
References:	Akaike H (1974) A new look at the statistical model identification. IEEE Trans Automat Control AC antioxidant status in diabetic rat lenses. J Biosci 30(2):221–230 Goldwaser I, Gefel D, Gershonov E, et al. Insulin-like effects of vanadium; basic and clinical implications. J Inorg Biochem. 2000;80:21–5. Joel SP, Clark PI, Heap L, Webster L, Robbins S, Craft H, Slevin ML Pharmacological attempts to improve the bioavailability of oral etoposide. Cancer Chemother Pharmacol 1995;37:125–133 K. Wo´zniak and J. B lasiak: “Vanadyl sulphate can differentially damage DNA in human lymphocytes and HeLa cells”, Arch. Toxicol., Vol. 78, (2004), pp. 7–15. M. Badea, R. Olar, V. Uivarosi, D. Marinescu, V. Aldea, S. F. Barbuceanu, G. M. Nitulescu; Thermal behavior of some vanadyl complexes with flavones derivatives as potential insulin-mimetic agents; J Therm Anal Calorim; 2011; 105:559–564 Margina, D.; Velescu, B.; Uivarosi, V.; Aldea, V.; Negres, S.; Mitrea, N., Evaluation of insulin-mimetic activity of new vanadyl-flavonoid complexes in alloxan-induced diabetes. FEBS JOURNAL, 277, p. 61, 2010. Negres S. Chirita C. New pharmacological model for inducing diabetes in rats. Farmacia 2012 (In press) Preet A, Gupta BL, Yadava PK, Baquer NZ (2005) Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses. J Biosci 30(2):221–230 Sakurai H, Katoh A, Kiss T, Jakusch T, Hattori M; Metallomics 2010; 2:670–682 Preet A, Gupta BL, Yadava PK, Baquer NZ (2005) Efficacy of lower doses of vanadium in restoring altered glucose metabolism and Subodh Verma, Margaret C. Cam and John H. McNeill; Nutritional Factors that Can Favorably Influence the Glucose/Insulin System: Vanadium; Journal of the American College of Nutrition, 1998 Vol. 17, No. 1, 11–18 U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry, Bioanalytical Method Validation. http://www.fda.gov/cder/guidance/4252fnl.pdf Viana GSB, Medeiros ACC, Lacerda AMR, Leal LKAM, Vale Tg, de Abreu Matos FJ, Hypoglycemic and antilipemic effect of aqueous extract from Cissus sicyoides. BMCPharmacology.2004;4-9 Watanabe S, Yamaguchi M, Sobue T, Takahashi T, Miura T, Arai Y, Mazur W, Wahala K, Adlercreutz H: Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soynean powder (kinako). J Nutr 1998, 128:1710-5 Wong E, Giandornenico CM. Current status of platinum-based antitumor drugs. Chemical Reviews. 1999;99(9):2451–2466. Xie M.J. Li L. Yang X.D. Liu W.P. Yan S.P. Niu Y.F. Meng Z.H. (2010) A new insulin-enhancing agent: [N,N′-bis(4-hydroxysalicylidene)-o-phenylene-diamine]oxovanadium(IV) and its permeability and cytotoxicity. 45:2327-2335 Y. Zhang, X.D. Yang, K. Wang and D.C. Crans: “The permeability and cytotoxicity of insulin-mimetic vanadium (III,IV,V)-dipicolinate complexes”, J. Inorg. Biochem., 2006, Vol. 100, pp. 80–87
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Article Title:	Pharmacodynamic and pharmacokinetic studies on novel vanadyl chrysin complex
Authors:	Bruno Stefan Velescu, Valentina Uivaroşi, Valentina Anuţa, Anca Buzescu, Simona Negreş
Affiliation:	Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Department of Inorganic Chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania Department of Physical chemistry, Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
Abstract:	A novel complex with general formula VO(chrysin) ·4H O was studied in order to evaluate its’ 2 2 pharmacodynamic action, and its’ pharmacokinetic properties. The hypoglycemic activity of the complex was evaluated in an alloxan diabetic rat model, and compared to chrysin and vanadyl sulphate. The pharmacokinetic properties were studied following a single dose administration, in compartmental and non-compartmental analyses. The complex has a low toxicity and a low hypoglycemic effect (p>0.05) correlated with the pharmacokinetic parameters (volume of distribution, half time and micro-constants).
Keywords:	vanadyl chrysin complex, pharmacodynamic action, pharmacokinetic properties, hypoglycemic activity
References:	Akaike H (1974) A new look at the statistical model identification. IEEE Trans Automat Control AC antioxidant status in diabetic rat lenses. J Biosci 30(2):221–230 Goldwaser I, Gefel D, Gershonov E, et al. Insulin-like effects of vanadium; basic and clinical implications. J Inorg Biochem. 2000;80:21–5. Joel SP, Clark PI, Heap L, Webster L, Robbins S, Craft H, Slevin ML Pharmacological attempts to improve the bioavailability of oral etoposide. Cancer Chemother Pharmacol 1995;37:125–133 K. Wo´zniak and J. B lasiak: “Vanadyl sulphate can differentially damage DNA in human lymphocytes and HeLa cells”, Arch. Toxicol., Vol. 78, (2004), pp. 7–15. M. Badea, R. Olar, V. Uivarosi, D. Marinescu, V. Aldea, S. F. Barbuceanu, G. M. Nitulescu; Thermal behavior of some vanadyl complexes with flavones derivatives as potential insulin-mimetic agents; J Therm Anal Calorim; 2011; 105:559–564 Margina, D.; Velescu, B.; Uivarosi, V.; Aldea, V.; Negres, S.; Mitrea, N., Evaluation of insulin-mimetic activity of new vanadyl-flavonoid complexes in alloxan-induced diabetes. FEBS JOURNAL, 277, p. 61, 2010. Negres S. Chirita C. New pharmacological model for inducing diabetes in rats. Farmacia 2012 (In press) Preet A, Gupta BL, Yadava PK, Baquer NZ (2005) Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses. J Biosci 30(2):221–230 Sakurai H, Katoh A, Kiss T, Jakusch T, Hattori M; Metallomics 2010; 2:670–682 Preet A, Gupta BL, Yadava PK, Baquer NZ (2005) Efficacy of lower doses of vanadium in restoring altered glucose metabolism and Subodh Verma, Margaret C. Cam and John H. McNeill; Nutritional Factors that Can Favorably Influence the Glucose/Insulin System: Vanadium; Journal of the American College of Nutrition, 1998 Vol. 17, No. 1, 11–18 U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry, Bioanalytical Method Validation. http://www.fda.gov/cder/guidance/4252fnl.pdf Viana GSB, Medeiros ACC, Lacerda AMR, Leal LKAM, Vale Tg, de Abreu Matos FJ, Hypoglycemic and antilipemic effect of aqueous extract from Cissus sicyoides. BMCPharmacology.2004;4-9 Watanabe S, Yamaguchi M, Sobue T, Takahashi T, Miura T, Arai Y, Mazur W, Wahala K, Adlercreutz H: Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soynean powder (kinako). J Nutr 1998, 128:1710-5 Wong E, Giandornenico CM. Current status of platinum-based antitumor drugs. Chemical Reviews. 1999;99(9):2451–2466. Xie M.J. Li L. Yang X.D. Liu W.P. Yan S.P. Niu Y.F. Meng Z.H. (2010) A new insulin-enhancing agent: [N,N′-bis(4-hydroxysalicylidene)-o-phenylene-diamine]oxovanadium(IV) and its permeability and cytotoxicity. 45:2327-2335 Y. Zhang, X.D. Yang, K. Wang and D.C. Crans: “The permeability and cytotoxicity of insulin-mimetic vanadium (III,IV,V)-dipicolinate complexes”, J. Inorg. Biochem., 2006, Vol. 100, pp. 80–87
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