• Sub-chronic Effect Of Co-administration Of Methformine And Amilodipine On Some Haematological Indices In Experimental Animal
    [A CASE STUDY OF WISTAR RATS]

  • CHAPTER FIVE -- [Total Page(s) 2]

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    • CHAPTER FIVE
      5.0 Discussion
      Metformin (1,1-dimethylbiguanide) is the most widely used drug to treat type 2 diabetes, and is one of only two oral anti-diabetic drugs on the World Health Organization (WHO) list of essential medicines (American Diabetes Association, 2009). Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP. Co-administration of Metformin and Amlodipine have been discovered to lead to vitamin B12 deficiency. Alterations in the blood parameters are considered to be one of the most reliable indicators of toxic effects of drugs, chemicals, heavy metals, etc. (Lodia and Kansala, 2012). In this study, the haematotoxicity of co-administration of metformin and amlodipine were assessed in relation to untreated (control) Wistar Rat.
       In the present study, Results of erythrogram showed decrease in haemoglobin (Hb), red blood cells (RBCs) count, packed cell volume (PCV) of Wistar rat treated with co-administration of metformin and Amlodipine (Figure 2 and Figure 3). The results obtained in this regards are consistent with the findings of (Takahashi- Iniguez et al., 2012). in exposed albino rat to 1mg/kg metformin-Amilodipine for 28 days. Expectedly there was a significant increase in mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) along with no effect on the mean corpuscular hemoglobin concentration (MCHC) (Figure 4). These observations have been reported by (Park et al., 2009). In these studies the red cell dependent parameters were negatively correlated to metformin-amlodipine dose. The differences observed in the various studies are attributed to difference in experimental model and design.
      In has been suggested that metformin-amlodipine intoxication induced oxidative stress in rat plasma with effect on red blood cells as evidenced by increased lipid peroxidation and alters the antioxidant system in several tissue, which may result in oxidative damage by inhibition of erythrocyte Na+-K+ ATPase. Also other mechanisms have been proposed such as Vitamin B12 deficiency. The decrease in hematocrit values and haemoglobin is confirmation of the synergistic link between the two blood parameters in all vertebrates.
      The current study indicates that oral exposure to metformin-Amlodipine significantly increase the total White Blood Cells count of Wistar Rat treated (Figure 5). Similar result was obtained by (Abdel-baky et al., 2013). The difference observed in previous study is attributed to difference in experimental model and design. Increase in white blood cell count might be due to intoxications and tissue necrosis due to the participation of Neutrophils and Monocytes in the process of phagocytosis as scavengers for wide variety of particulate material (El-Demerdash et al., 2004). Moreover, the increased Neutrophils to lymphocytes ratio are an indicator for a systemic inflammation. It was clearly demonstrated that oral exposure to metformin-Amlodipine increases the Neutrophils/Lymphocytes ratio which might be due to the oxidative stress outcomes of co-administration (Gosslau et al., 2014). Regarding to platelet count there was decrease in platelet count of metformin-amlodipine treated group compared to the control group (Figure 6). This was also recorded by Abdel-baky et al., 2013. For the explanation we will err on the evidences provided by earlier researchers that there is possibility of destruction of platelet during continuous administration of metformin-amlodipine by the fall in the number and increase in their cell size of individual platelets.
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    • ABSRACT - [ Total Page(s): 1 ]ABSTRACTMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009) whereas Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP (Blood pressure). the aim is to know the effect of co-administration of this two drugs in Wistar rats ... Continue reading---

         

      APPENDIX A - [ Total Page(s): 1 ]APPENDIXAPPENDIX 1:     MATERIAL USED1% Ammonium oxalate10% Formalin salineAbsorbent paperAutomatic pipetteBrilliant cresyl blueCounting chamber Cyanmethaemoglobin standardDrabkin’s ReagentEDTA sample containerHematoxylin and Eosin stainKhan tubes/rackLeisfhmann stainLight microscopeMicrohaematocrit centrifugeNormal salinePasteur pipettePipette tipsRotary microtomeSpectrophotometerTimer Turk’s solution Universal sample bottle ... Continue reading---

         

      APPENDIX B - [ Total Page(s): 1 ]APPENDIX IITable 1: haematological parameters in control, Metformine treated and Amilodipine treated Rats (Values are expressed as mean ± Standard error of means)                     Group A(1): control (untreated), Group B(2): co-administration of Metformin 0.00264/ml/132g and Amlodipine 0.000849/ml/132g at a single dose for 30 daysPARAMETERS     GROUP A     GROUP   BPacked cell volume (%)    44.16±2.83    38.47±3.53Red blood cell count (x1012/L)    7 ... Continue reading---

         

      LIST OF TABLES - [ Total Page(s): 1 ]LIST OF TABLESTable 1: Haematological parameters in control, Co-administration of Metformin and Amlodipine treated  ... Continue reading---

         

      LIST OF FIGURES - [ Total Page(s): 1 ]LIST OF FIGURESFigure 1: Shows mechanism of action of metformin Figure 2: Shows Pie chat representation of Packed cell volume of control, Co-administration of metformin and amlodipine treated Wistar Rats        Figure 3: Shows Histogram representation of Hemoglobin and red blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats   Figure 4: Shows Histogram representation of red cell indicies of control, Co-administration of metformin and amlodipine t ... Continue reading---

         

      TABLE OF CONTENTS - [ Total Page(s): 1 ]TABLE OF CONTENTTitle page   Declaration  Certification  Dedication     Acknowledgement      Table of content      List of table  List of figures     Abstract    CHAPTER ONE1.0 Introduction    1.1 Background of study   1.2 Statement of Problems           1.3 Justifications    1.4 Aims      1.5 Research Objectives       1.6 Research Hypothesis     1.7 Significance of research   CHAPTER TWO2.0 Literature review    2.1 Metformin    2.1.1 ... Continue reading---

         

      CHAPTER ONE - [ Total Page(s): 2 ]CHAPTER ONE1.0    INTRODUCTION1.1 Background of the studyMetformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009). Currently, many clinical practice guidelines for patients with type 2 diabetes, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes ... Continue reading---

         

      CHAPTER TWO - [ Total Page(s): 12 ]The current use of serum Vitamin B12 level relies on several different range points for Vitamin B12 status. Serum Vitamin B12 level under 148 pmol/L are said to be deficient, low/borderline levels are interpreted from levels between 148-220 pmol/L (Mazokopakis and Starakis, 2012). Normal ranges of Vitamin B12 serum range from 220- 800 pmol/L, levels that exceed this are rarely suspicious in cause, although excessive B12 serum may be a marker of myloproliferative disorders (Pernicova and Korbonit ... Continue reading---

         

      CHAPTER THREE - [ Total Page(s): 4 ]From the above table,Km of rats= 6    Km of human= 37For Amlodipine, Human dose= 10mg/70kg                                        1kg=10/70                     =0.14mg/kgAED of Amilodipine= 0.14×(6/37)                                  =0.02mg/kgAverage weight of experimental Animal is 132g(0.132kg)If 0.02mg of Amlodipine is administered per kg.bw,(0.02×0.132)mg of Amlodipine was administered to ... Continue reading---

         

      CHAPTER FOUR - [ Total Page(s): 6 ]CHAPTER FOUR4.0 Results4.1 Hematological parameter in control and test groups    As summarized in table 1, the mean RBC counts were 7.62 ± 2.83 x1012/L for the control and 6.53 ± 0.57 x1012/L for co-administration of metformin and amlodipine fed groups respectively. Although, decrease in RBC counts was observed in the treated (co-administration of metformin and amlodipine) dose group, these were statistically significant compared to control groups (student t test P0.05) higher in the tr ... Continue reading---

         

      REFRENCES - [ Total Page(s): 4 ]Senol, M.G., Sonmez, G., Ozdag, F. and Saracoglu, M. (2008). Reversible myelopathy with vitamin B12 deficiency. Singapore Medical Journal. 49(11): 330-332.Srinivasan, S., Ambler, G.R., Baur, L.A., Garnett, S.P. and Tepsa, M. (2006). Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Journal of Clinical Endocrinology and Metabolism. 91: 2074-2080. Sterne, J. (1957). Du nouveau dans les anti ... Continue reading---