UREA AND CREATININE CONCENTRATIONS OF PLASMODIUM BERGHEI INFECTED MICE TREATED WITH COARTEM, HIPPROCRATEA AFRICANA ROOT BARK EXTRACT, CIPROFLOXACIN AND JATROPHA TANJORENSIS

UREA AND CREATININE CONCENTRATIONS OF PLASMODIUM BERGHEI INFECTED MICE TREATED WITH COARTEM, HIPPROCRATEA AFRICANA ROOT BARK EXTRACT, CIPROFLOXACIN AND JATROPHA TANJORENSIS

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ABSTRACT

The concomitant effect of Hippocratea africana root bark extract, Jatropha tanjorensis Ciprofloxacin and Coartem on markers (Urea and Creatinine) of Kidney function in Plasmodium berghei infected adult male mice was investigated. Thirty (30) adult male mice were used for the study. They were randomly divided into ten (10) groups of three (3) animals each. Group I animals served as the control group and were given 1ml distilled water. Group II animals served as the test control parasitized but not treated and were given 1ml of distilled water. Group III animals (non-parasitized) were administered Jatropha tanjorensis (1161.89mg/kgbw) for 5 days. Group IV animals were parasitized and treated with Hippocratea africana (200mg/kgbw) for 4 days. Group V animals were parasitized and treated with Hipprocratea africana (200mg/kgbw) for 4 days and Jatropha tanjorensis (1161.89mg/kgbw) for 5 days. Group VI aanimals were parasitized and treated with Hippocratea africana (200mg/kgbw) for 4 days, Ciprofloxacin for 5 days. Group VII animals were parasitized and treated with Hippocratea africana (200mg/kgbw) for 4 days, Ciprofloxacin for 5 days and Jatropha tanjorensis (1161.89mg/kgbw) for 5 days. Group 8 animals were parasitized and treated with Coartem (8mg/kgbw) for 3 days. Group IX animals were parasitized and treated with Coartem (8mg/kgbw) for 3 days and Jatropha tanjorensis (1161.89mg/kgbw) for 5 days. Group X animals were parasitized and administered Coartem (8mg/kgbw) for 3 days, Ciprofloxacin for 5 days. All the drugs were administered orally once daily by use of canular attached to a syringe. All the experimental animals were given normal mice chow and H2O ad libitum throughout the treatment period. The result showed a significant (p<0.05) decrease in serum creatinine levels in the experimental animals treated with concomitant administration of Coartem and Jatropha tanjorensis. Serum Urea levels also showed significant (p<0.05) reduction in the experimental groups treated with the herbs. Although, significant (p<0.05) increase is urea levels were obtained in experimental mice treated with co-administration of Ciprofloxacin and the herbs. The reduction in the marker of renal function implies that the herbs is nephroprotective and may be safe for its use as antiplasmodial agents. The increase in serum urea levels observed for the ciprofloxacin – treated groups infer a derangement in organ function by the antibiotic drug.

Key Word: Ciprofloxacin, Coartem, Creatinine, Hippocratea africana,

Kidney function, Jatropha tanjorensis, Urea.


CHAPTER ONE

1.0             INTRODUCTION

1.1     Background of Study

Malaria is one of the most common infectious diseases and a great public health problem worldwide, particularly in Africa and South Asia. Malaria is associated with enormous health problem with enormous health and economic consequences. It is one of the major parasitic diseases in the tropics, responsible for significant morbidity especially among children and pregnant women. It is estimated that 1 to 2 million people die yearly as a result of malaria (Sudhanshu et al., 2003). A WHO (2008) report stated that Nigeria accounts for a quarter of all malaria cases in Africa. In the Southern part of Nigeria, transmission occurs all year round while in the north it is mostly seasonal (Adebayo and Krettli, 2011).

Malaria is a mosquito-borne infectious disease of humans and other animals. It is caused by parasitic protozoans belonging to the genius Plasmodium (WHO 2014). In humans, malaria is caused by Plasmodium falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi (Mueller et al., 2007; and Collins, 2012).  P. falciparum is the most dangerous and commonest species and was identified in 75% of affected individuals, found in 20% of patients (Nadjm and Behrens, 2012).

Transmission

          The female anopheles mosquito transmits the parasite, Plasmodium falciparum, by first ingesting them when feeding on an infected person’s blood and then injecting them when biting another person (Agrawal et al., 2005). The parasite has a complex life cycle. On entering a human host, the parasite invades a liver cell, takes on a new form and makes copies of it. Eventually, the liver cell ruptures and releases the parasites to the bloodstream where they infect red blood cells. Within the blood cells, most parasites reproduce again, which kills the cells, and the parasites then invade more blood cells. Other parasites, while in the blood cells, develop into male and asexual forms. When these cells are ingested by a mosquito, the cells burst freeing the sexual forms of the parasite. Within the mosquito, the two forms merge to create an oocyst. After maturing, the oocyst ruptures to release thousands of parasites which migrate to the mosquito’s salivary gland awaiting her next bite (White, 1999).

Signs and Symptoms

          The signs and symptoms of malaria typically begin 8 - 25 days following infection (Fairhurst and Wellems, 2010). However, symptoms may occur later in those who have taken antimalarial medications as prevention (Nadjm and Behrens, 2012).  Initial manifestations of the disease – common to all malaria species – are similar to flu – like symptoms, and can resemble other conditions such as sepsis, gastroenteritis, and viral disease (Bartoloni and Zammarachi, 2012). The presentation may include headache, fever, shivering, joint pain, vomiting, hemolytic anaemia and jaundice, hemoglobin in the urine, retinal damage and convulsions (Beare et al., 2006).

Prevention

There is no vaccine for malaria. The presence of malaria in an area requires a combination of high human population density, high anopheles mosquito population density and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite will eventually disappear from that area, as happened in North America, Europe and parts of the Middle East. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favours the parasite’s reproduction. Furthermore, the cost per person of eliminating anopheles mosquitoes rises with decreasing population density, making it economically unfeasible in some areas (WHO, 1958). Prevention of malaria may be cost-effective than treatment of the disease in the long run, but the initial costs required are out of reach of many of the world’s poorest people.

Treatment

          The treatment of malaria has faced several challenges due to development of resistance by the parasite (Yeung et al., 2004), affordability and efficacy of antimalarial drugs (Ndem et al., 2013 and Ebong, 2014). Cytotoxicity and side effects of antimalarial drugs also contribute to these challenges in the treatment of malaria (Rates, 2011). African countries have recently begun to scale up their antimalarial efforts, and are deploying strategies to combat the new face of malaria. One of these strategies is the use of artemisinin-based combination therapies (ACTs) which have proven to be very effective against malaria in Africa, and some African countries with resistant forms of P.falciparum have started instituting the ACTs as first line malaria treatment. ACT decreases resistance to any single drug component (Kokwaro, 2009).

          Although ACT is the current WHO recommended modality of malaria chemotherapy (White, 1999), some factors have been reported to limit ACT’s use such as its high cost, limited production of artemisinin-derivative, Good  Manufacturing Practices (GMP) Standards, toxicity and others (Haynes, 2001; Boareto et al., 2008; and Adebayo and Malomo, 2002).

          Herbal usage seem necessary due to the resistance of the malaria parasite to conventional antimalarial drugs and persistence of malaria symptoms after treatment with these antimalarial drugs. Some of these herbs are the Hippocratea africana and Jatropha tanjorensis. The Hippocratea africana (Hippocrateaceae), is a green forest perennial climber without hair and reproducing from, seeds (Dalziel, 1956). The root of the Hipprocratea africanna plant is used traditionally in the treatment of various ailments such as fever, malaria, body pains, diabetes, and diarrhea (Okokon et al., 2006).

          The Jatropha tanjorensis belongs to the family Euphorbiaceae, it is a common weed of field crops, bush re-growth, road sides and disturbed places in the higher rainfall forest zones of west Africa. It is commonly called hospital too far, catholic vegetable, iyana-ipaja, lapalapa (Iwalewa et al., 2005). The leaf is commonly consumed as vegetable in many parts of Southern Nigeria. It is used traditionally in the treatment of malaria, fever, inflammation, etc. and it is also known to provide the body system with blood.

          Orthodox drugs are also use in treating malaria an example is the Ciprofloxacin. Ciprofloxacin affects Plasmodium falciparum by causing the formation of an abnormal apicoplast and a delayed death of treated parasites (Dahl EL et al., 2007). Many studies have shown that ciprofloxacin displayed the best in vitro anti-malarial activity.

1.2     Aim of the Study

          The aim of this study is to examine the Kidney function of Plasmodium berghei infected mice of treated with Hippocratea africanna root bark extract, Ciprofloxacin and Jatropha tanjorensis.

1.3     Objectives of the Study

The specific objectives of this study are:

·        Preparation of ethanolic extract of Hippocratea africanna.

·        Administration of the Hippocratea africanna plant extract to four (4) groups of mice.

·        Preparation of the ethanolic extract of Jatropha tanjorensis.

·        Administration of the Jatropha tanjorensis plant extract to five (5) groups of mice.

·        Preparation of the Ciprofloxacin

·        Administration of the Ciprofloxacin to three (3) groups of mice.

1.4     Justification of Study

Interest in medicinal plants as re-emerging health therapy have been fuelled by the rising costs of prescription drugs in the maintenance of personal health and well-being, and the bio prospecting of new plant-derived drugs (Hoareau and Dasila, 1999). One of such refocus interest in Africa, especially Nigeria (in both urban and rural areas) is herbal treatment for diseases. Despite the many orthodox drugs in the market, the upsurge in the number of people that rely on herbs for treating ailments has necessitated increased efforts to authenticate the efficacy and safety of some herbal claims. Some of those herbs are Hipprocratea africanna and Jatropha tanjorensis roots barks which are used traditional especially in the Southern part of Nigeria for the treatment of Malaria. Malaria is a worldwide public health problem with the enormous health and economic consequences. This is because of the unavailability and unaffordability of Artemisinin Combination Theraphy (ACT) that has been recommended by the World Health Organization (WHO) for the treatment of malaria, as well as resistance to malaria chemotherapeutic agents, resulting in re-occurrence of the disease few weeks after treatment.

          Despite the promising schizontocidal properties of Hipprocratea africanna and Jatropha tanjorensis as well as good reports on biochemical and toxicological indices, information on their effects on renal function is inadequate hence this study to ascertain its toxicity to the renal system.

1.5     Scope of Study

          The scope of this study includes:

§  Botanical identification of plants materials.

§  Preparation of plant extracts and drugs for administration.

§  Acute toxicity study of plant and determinant of LD50 for Jatropha tanjorensis.

§  Assessment of weight changes, parasite count and hematological indices of mice following drugs and herbal treatments. 


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