THE EFFECT OF LONG TERM ADMINISTRATION OF ARTEMETHER/LUMENFANTRINE ON SEMEN QUALITY AND HISTOLOGY OF THE TESTIS IN ALBINO MICE  

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                                                           ABSTRACT

This study was designed to investigate the effects of long term administration of Artmether/Lumenfantrine  on semen quality and histology of the testis  in albino mice. This study lasted for twenty-three (23) days, within which the mice were acclimatized, inoculated with Plasmodium  berghei  parasite, administered with Artemeter/Lumenfantrine and sacrificed. A total of twenty five (25) mice were used for the study and were grouped into five groups (n=5) with five mice per group. All the mice were fed with rat chow and clean drinking water, under regulated environmental factors such as temperature. Group ‘A’ mice were used as the control mice. Group ‘B’ mice were infected with malaria.  Group ‘C’ mice were infected with malaria and treated once with 56mg/kg of Artemether/Lumenfantrine. Group ‘D’ mice were infected with malaria and treated  twice with 56mg/kg of Artemether/Lumenfantrine. Group ‘E’ mice were infected with malaria and treated thrice with 112mg/kg of Artemether/Lumenfantrine. The drug was administered to the animals as solution using orgastric tube. The dosage was 56mg/kg Artemether/Lumenfantrine administered twice daily between an 8-hour interval for two days. This treatment of malaria was done on three occasions, which connoted the short-term, middle-term, and long-term administration of Artemether/Lumenfantrine. Upon sacrificing the mice,  to show the effect of long term administration of artemether/ lumenfantrine on semen quality and histology of the testis  the results were rendered using ± SEM and statistically analyzed using ANOVA with significant level (p<0.05). Comparing  the  results,  of a normal albino mice and infected malaria albino mice showed significant decrease (p<0.05) when compared to control group. However, it is noteworthy that long term administration can decrease the quality of semen and the histology of the testis.

 

TABLE OF CONTENTS

TITLE PAGE      –       –       –       –       –       –       –       –       –    i

CERTIFICATION        –       –       –       –       –       –       –       –    ii

DEDICATION    –       –       –       –       –       –       –       –       –   iii

ACKNOWLEDGEMENT      –       –       –       –                –       –   iv

ABSTARCT        –       –       –       –       –       –       –       –       –    v

TABLE OF CONTENT –       –       –       –       –       –       –   vi

 

1.0    INTRODUCTION        –       –       –       –       –       –       –  1

1.1    Background of study –       –       –       –       –       –  1

1.2 Research problem        –       –       –       –       –       –       –  3

1.3 Scope of study     –       –       –       –       –       –       –       –  4

1.4 Aim and objectives of study –       –       –       –       –       –   5

1.5 Justification of study   –       –       –       –       –       –       –   5

1.6 Significance of study    –       –       –       –       –       –       –   6

CHAPTER TWO

2.0    LITERATURE REVIEW       –       –       –       –       –       –   7

2.1 Anatomy of the Male Reproductive System   –       –       –   7

2.1.0  Scrotum  –       –       –       –       –       –       –       –       –   7

2.1.1 Testes       –       –       –       –       –       –       –       –       –   7

2.1.2  Epididymis      –       –       –       –       –       –       –       –   8

2.1.3  Spermatic Cords and Ductus Deferens      –       –       –   8

2.1.4  The ductus deferens         –       –       –       –       –       –   9

2.1.5  Seminal Vesicles      –       –       –       –       –       –       –   9

2.1.6  Ejaculatory Duct      –       –       –       –       –       –       –   9

2.1.7 Urethra    –       –       –       –       –       –       –       –       –  10

2.1.8  Prostate   –       –       –       –       –       –       –       –       –  10

2.2 Cowper’s Glands  –       –       –       –       –       –       –       –  10

 

2.2.1 Penis        –       –       –       –       –       –       –       –       –  11

2.2.2 The human semen    –       –       –       –       –       –       –  11

2.2.3 Physiology of the Male Reproductive System       –       –  15

2.2.3.1 Spermatogenesis    –       –       –       –       –       –       –  15

2.2.3.2 Testosterone  –       –       –       –       –       –       –       –  16

2.2.4 Fertilization      –       –       –       –       –       –       –       –  16

2.2.5 Male Infertility –       –       –       –       –       –       –       –  17

2.2.6 Medical causes –       –       –       –       –       –       –       –  17

2.2.7 Environmental causes       –       –       –       –       –       –  20

2.2.8 Radiation or X-rays.  –       –       –       –       –       –       –  21

2.2.8 Malaria     –       –       –       –       –       –       –       –       –  23

2.2.8.1 Symptoms of malaria     –       –       –       –       –       –  25

2.2.8.2 Causes of  malaria –       –       –       –       –       –  26

2.2.8.3 Preventing malaria –       –       –       –       –       –  27

2.2.8.4 Treating malaria     –       –       –       –       –       –       –  28

2.2.8.5 Complications of malaria        –       –       –       –       –  28

2.2.9  Malaria and the human immune system   –       –       –  29

2.3 Effects of Malaria on the Cardiovascular System   –  30

2.3.1 Effect of malaria on the renal system –       –       –  31

2.3.2 Chemical Balance     –       –       –       –       –       –       –  31

CHAPTER THREE

3.0 Materials and Methods –       –       –       –       –       –  36
3.1.  Locations  –       –       –       –       –       –       –         –     –  36

3.2 Inoculation of Malaria Parasite     –       –       –       –       –  37

3.3 Determination of Parasitemia       –       –       –       –       –  37

3.4 Experimental Design    –       –       –       –       –       –       –  38

3.5 Animal Treatment        –       –       –       –       –       –       –  39  3.6 Drug Administration    –       –       –       –       –       –       –  39

3.6.1 Artemether/Lumefantrine –       –       –       –       –  39

3.7 Collection of Sample    –       –       –       –       –       –       –  40

3.8 Procedure for semen Analysis       –       –       –       –       –  40

3.9    Sperm Count   –       –       –       –       –       –       –       –  40

3.10  Sperm motility  –       –       –       –       –       –       –       –  41

3.11  Sperm morphology   –       –       –       –       –       –       –  41

3.12  Hormonal Assay        –       –       –       –       –       –       –  42

3.13  Preparation of Tissues for Histological Analysis           –  42

3.14      Photomicrography –    –      –     –      –      –      –     – 43

3.15      Analysis –      –   –    –    –     –     –       –      –      –    43

CHAPTER FOUR

4.0    RESULTS          –       –       –       –       –       –       –       –  44

4.1    The Effect of Artemether/Lumefantrine on

Sperm count of Malaria infected mice –       –       –  44

4.2    The effect of Artemether/Lumefantrine on percentage  47

of normal Sperm motility of Malaria infected mice

4.3    The Effect of Artemether/Lumefantrine on percentage 47

of normal Sperm morphology of Malaria infected mice.

 

 

CHAPTER FIVE

5.0    DISCUSSION, CONCLUSION AND RECOMMENDATION      –         –       –       –       –       –       –       –       –       –  49

5.1    Discussion        –       –       –       –       –       –       –       –  49

5.2    Conclusion        –       –       –       –       –       –       –       –  51

• Recommendation –       –       –       –       –       –       –  51

REFERENCES   –       –       –       –       –       –       –       –  52

 

 

CHAPTER ONE

1.0    INTRODUCTION

1.1    Background of study    

Malaria is a global disease that is predominant in the tropic and cause by the blood parasite, plasmodium oval, plasmodium falciparum, plasmodium malariae, and plasmodium vavix. Malaria has a great morbidity and mortality than any other infectious disease of the world (Hall 1998; WHO, 2000). Commonly, the disease is transmitted by a bite from an infected female Anopheles mosquito, which introduces the organisms from its saliva into a person’s circulatory system. In the blood, the parasites travel to the liver to mature and reproduce. Malaria causes symptoms that typically include fever and headache, which in severe cases can progress to coma or death. Survey show that 90℅ of the world cases of malaria occur in sub-Saharan Africa (WHO, 2005).Nine out of ten cases in this disease occur in this region and record over one million death (Smith, 1978). Malaria is typically diagnosed by the microscopic examination of blood using blood films, or with antigen-based rapid diagnostic tests. Modern techniques that use the polymerase chain reactionto detect the parasite’s DNAhave also been developed, but these are not widely used in malaria- endemicareas due to their cost and complexity.( Weinke et al., 1991)  Malaria in Nigeria is endemic and constitutes a major health problem. Despite the curable nature of the disease, malaria related death outcome account up to 11% 0f maternal mortality, 25% of infant mortality and 30% of under five year of mortality (WHO, 2012), resulting in about 300,000 childhood death annually. The vast majority of the death occur among children under five years of age and pregnant women (Philips, 2011), especially in remote rural area with poor access to health.  initial manifestations of the disease—common to all malaria species—are similar to flu-like symptoms, (Agbenyega and Zammarchi 2012) and can resemble other conditions such as septicemia, gastroenteritis, and viral diseases. The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions (Beareet al.,2006).

  The combination artemether/lumefantrine is a fixed-dose combination artemisinin-based combination therapy (ACT) indicated for the treatment of acute uncomplicated Plasmodium falciparum malaria (Abdullaet al.,2008). is safe and well tolerated; majority of its adverse events are of mild or moderate severity mostly affecting gastrointestinal and nervous systems; however, most are typical of the symptomatology of malaria or concomitant infections (Abdulla et al., 2008; Gemperli et al., 1999Nothdurft et al., 2008; Falade et al., 2005). Although Artemether/lumefantrine possesses similar chemical structure with halofantrine which is known to cause cardiac arrhythmia and sudden death, safety studies have not shown lumefantrine to be cardiotoxic or to prolong QTc interval at therapeutic doses (Norvatis, 2008; Manyando et al., 2009).

Artemether/lumefantrine can cause anaphylactic reactions. The drug frequently causes headache, dizziness and anorexia, although mild forms in most cases. Other fairly common side effects (more than 3% of patients) include sleep disorder, tinnitus, tremor, palpitation, as well as unspecific reactions like vertigo, gastrointestinal disorders, itch and nasopharyngitis (Abdulla, 2008).