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HISTOLOGY OF THE SPLEEN OF ADULT WISTAR RATS FOLLOWING ADMINISTRATION OF ARTESUNATE

This is a project report on the Histology of the Spleen of Adult Wistar Rats Following Administration of Artesunate.


CHAPTER ONE

1.0 INTRODUCTION

1.1 BACKGROUND OF STUDY

Artesunate the drug of study is a water soluble derivative of artemisinin which was extracted from the leaves of the Chinese herbal plant Artemisia sannua and sweet worm-wood. Archaeological finding indicates that this herb has been in use as a traditional remedy for the treatment of malaria fever in china as far back as 340A.D (Klayman, 2002). Artesunate is an effective, potent and rapidly acting blood schizonticide, a parasitidal of the asexual stage and has maintained activity even in patients with multi-drug resistance to malaria parasite (Kumar, 1999).

Humans have always co-existed with parasites. Even in medieval times it was believed that using large amount of herb, spices, perfumery material e.g. sandal wood incense etc afforded protection from mosquitoes and subsequently malaria, the infectious disease caused by these mosquitoes (Mann, 2000).

Malaria is caused by the protozoan parasite of the genus plasmodium, it is one of the widest disease affecting human populations especially in the tropics. Approximately 300-500million people are infected each day and 1.5-2.7 million lives are lost annually due to malaria.

These are 4 species of protozoa which include plasmodium vivax, plasmodium ovale and plasmodium falciparum which is the most dangerous with a very high morbidity rate. When not properly treated leads to fatal cerebral malaria especially in children (Rayness, 1999).

Plasmodium parasite has a complex lifestyle that is shared between an insect vector and a vertebrate host. The parasite enters the body through the bite of infected female anopheles mosquitoes as the males do not feed on blood but on plant juice. Like all mosquitoes, the anopheles breeds in water with their own peculiar feeding habit, breeding ground and resting places (Mann, 2000).

Plasmodium develops in the gut of the anopheles and is passed on each time it takes a blood meal. The parasite when passed during blood meal is carried in the blood to the liver where they invade cells and multiply. The parasite takes the form of sporozoites when freshly infected, but on reaching the liver cells where they undergo multiplication through asexual reproduction they change to merozoites which when released from the liver will re-infect and penetrate the red blood cells (Bloland, 2011). The merozoites then differentiate into trophozoites which devour 70% of the haemoglobin in RBC in order to replicate its nucleus. During this process, the parasite is known as a schizont. Cytoplasm and membranes develops on these schizonts producing 12-28 merozoites which cause the eventual lyses of the erythrocytes releasing more merozoites. This causes several cycles of chills and fever every 36 hours with substantial malaria (Rayness, 1999).

Headache, muscle aches, tiredness, nausea and vomiting symptoms of the disease which often occurs. Jaundice and anaemia may occur due to loss of red blood cells, thus leading to yellow coloration of the skin and eyes. It could also result in kidney failure, coma and finally death is very severe cases when not properly treated (Ollario, 2001).

Merozoites may also differentiate into macro and micro gametocytes which do not rupture erythrocytes but are ingested when another mosquito take a new blood meal from an infected person. It develops into male and female gametes which fuse to form a diploid ookinetic. This ookinete penetrate the mosquitoes gut wall where it develops into an oocyts. This oocyst when ruptured migrate to the salivary gland for onward infection into another host, hence the cycle begins again (Bloland, 2001).

Malaria has been known since time immemorial but it was centuries later that the causative agent was known. Drugs such as miasma drugs became less effective following malaria resistance to their usage, coupled with undesirable side effects. Thereafter chloroquines first line usage as a treatment became limited following evolution of plasmodium vivax resistance recorded in 1989 (Ridley, 2002) and some side effects which includes blurred vision, seizures and polyneuritis.

Also the use of antifolate drugs like pyrimethamine sulphadoxine combination under the brand names fasidar, malareich etc also became discouraging because of such effects like skin rashes, neuromyopathy etc. couple with plasmodium falciparum resistance to the drug recorded in places like the Amazon basins of South America and parts of Ethiopia in Africa (Ridley, 2002).

Due to the decline recorded in the existing drugs as well as steady negative statistics gathered by WHO, it became imperative to researcher on different fields to produce more effective drugs with less toxic side effects.

This result paid off during the Vietnamese war, where the scourge of malaria in the battle field led Ho Minh Chi the Vietnamese leader to seek the help of his Chinese counterpart Mao to seek for cure. This Chinese report and research brought to our knowledge the presented drug of study, ARTESUNATE.

Artesunate, our drug of study is a water soluble semi-synthetic hemisuccinate derivative of Artemisinin. It is also the most effective and rapidly acting of the family of anti-malaria drugs because of its bioavailability. It is synthesized by reaction dihydro artemisinin and succinic acid anhydride in an alkaline medium. Thus, this reaction gives an ester linkage on alpha configuration (Bharel, 1996).

It is highly and rapidly converted to dihydro-artemisinin in the gastro-intestinal tract and blood. It’s absorbed within minutes and distributed in tissues, where it’s metabolized. It is formulated for oral, parenteral and rectal administration. Though it is unstable in neutral solution, it is available as artesunic acid for injections. Artesunate is an effective, potent and rapidly acting blood schizonticide and has maintained activity when used in curing patients.

Since most drugs, including artesunate exhibit a variety of sub-lethal effect on some organs as have been deserved in mammals. Such organs as the spleen, kidney and liver as well as the central nervous system may be affected in their function and histology. Thus, this brings us tour organ of study “THE SPLEEN”.

The spleen is a lymphoid and highly vascularized organ. It is covered by an outer serous coat and the inner capsule which is fibromuscular. It functions for the production of blood cells (T and B lymphocytes) which plays important role in the immune system. Other functions include storage of blood, destruction of worn out red blood cells, production of blood cells in fetal life etc. so, artesunate will have a way of altering the histology of the spleen as it tries to perform the aforementioned function. E.g. in an earlier study of the effect of administration of lindane on the histology of the spleen of adult wistar rats, the results obtained shows that increased dose of lindane is detrimental to the spleen, and can cause malfunction of the immune system.

1.2 SIGNIFICANT OF THE STUDY

Most drugs are often taken without knowledge of their side effect, hence the need for this study.

A drug can be defined as any substance, product or compound used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient (Bernard, 2000). According to Goth 1995, a drug can be regarded as any chemical substance or compound used in the diagnosing, prevention and treatment of disease.

Drugs are accessed not only from a scientific point but also from health care delivery to the populace. Artesunate is being recommended as the best anti-malaria drug with little or no side effects that are not desirable apart from the usual dizziness, nausea and vomiting which are sympathetic of malaria. According to Boland (2001) “no major side effect of this drug artesunate has been reported, though high parental dose in rats led to selective brain stem pathology”.

In this vein, a non-toxic dose and side effects of this drug is of utmost important to the clinician. Hence, it is hoped that information obtained from this research work will go a long way in pointing out the problem and effects associated with the consumption of this drug in other to advice the populace as such.

1.3 AIM/OBJECTIVE OF STUDY

The present study is designed to invest the possible changes which may occur to the morphology, physiology and histology of the spleen following varied dosage and time duration of the drug through oral route.

The result obtained is aimed at determining the toxic effects if any kind that may be associated with the use of this drug and the consequent effect that is obtained over dosage or abuse of this drug.

1.4 SCOPE OF THE STUDY

The scope of this study is limited to the histology of the spleen of adult wistar rats under light microscope following administration of artesunate.

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Topic: Histology of the Spleen of Adult Wistar Rats Following Administration of Artesunate.

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