Hepatoproductive Effects Of Sena Tora Leave Extract On Carbon Tetrachloride Induced Toxicity

Hepatoproductive Effects Of Sena Tora Leave Extract On Carbon Tetrachloride Induced Toxicity

Abstract

The aim of this study is to find out hepatoproductive effects of senna tora leaf extract on carbon tetrachloride induced toxicity. Thirty albino rats were used for the study, they were housed in super rate cages and acclimatized for two days and them divided into six groups of five rats each. Group 3: was injected with high aloes 1000mg/kg body weight of the plant leaves extract after prior exposure (I.P) to the toxicant (CCL4) single dose of toxicant. Groups 4 and 5 were injected 1P with a single dosing vehicle in corn oil as a standard dose of vehicle in the ratio of 3:1 (Corongui and Manilra, 1983). Groups 2 and 3 were treated with extract alone and allowed to survive for 2 days before sacrifice. Group 5: was treated with mid dose 100mg of the methanolic extract of the plants leaves after exposing the animals to CCL4 single dose. The results of the total cholesterol levels reduced significantly (P0.05) in the group administered low dose of the extracts to the animals when compared with the negative control. The administration of low dose (500 mg/kg/day) of extract to the rats after exposing them to the toxicity was found to increase the levels of serum cholesterol, but at high dose of CCL4, the reverse was the case (reduced). The results disclosed in this work suggest that the methorolic extract of plant leaves has the potential efficacy in protecting tissues and organs from peroxidative damage.

Chapter One

1.0 Introduction

Many of the developing countries including African countries like Nigeria practice traditional medicine as its main source of health care. This traditional medicine is normally gotten from plant origin [Rehan Ahmad et al, 2008, Stephen bent, 2008].Today nearly 88 percent of the global populations switch to plant derived medicines as their first line of defence for maintaining health and combating diseases [Kintzois et al,2006]. Presently there are about 60 types of medicinal plants that have been recognised in primary health care and are classified according to their pharmacological actions such as peptic ulcers, anti flatulence, laxative, anti diarrhoea and anti hepatic[Viomolos et al,2003]. However in future the discovery of novel therapeutic agents will be only dependent on plant origin [Perulmalsamy et al, 1999]. Senna tora is an example of traditional medicine with pharmacological actions as anticholesterolemic,antispasmodic,carninitative, emolliants, ophthalmic and purgative [Polunin and Stanton,1984,Yeung,1985,Manandhar, 2002].

It can be cardiotonic, antiperiodic, anthelminitic and expectorant and can also be used in treating cogh,leprosy ,ring worm ,colic,flatulence,constipation and other disorders[Nature serve,2007]. Senna tora formally regarded as cassia tora is capable of suppressing the production of prostaglandins and other inflammatory agonists such as cytokines, histamine, kinin and free radical.manila,1998 buttressed his observations confirming its use in the treatment of constipation, edema and liver protection in Korea. Liver, the largest internal organ of the human body performs more than five hundred functions, all of which are very vital to life. The liver can regenerate or grow back cells that have been destroyed by short term injury or disease, but if the liver is damaged repeatedly over a long period of time, it may undergo irreversible changes which permanently interferes with its function. Carbon tetrachloride is a toxic substance that interrupts the liver and its functions.

This is to say that it damages the liver when ingested.CCL4 is stable in the presence of air and light, it is also inflammable. Despite its toxic effect on the liver, it is useful as grain fumigant ,pesticide etc. Equilibrium of the body fluids and secretions are altered as a result of carbon tetrachloride. For instance lipid metabolism, cholesterol metabolism and biotransformation functions of the liver are terminated or altered in the presence of CCL4.Thus carbon tetrachloride is lethal. The liver produces some enzyme such as aspartate amino transaminases, alkaline phosphatase, lactate dehydrogenase,gamma glutamyl transsferase etc which catalyses the biochemical activities of the body, and on the attack of CCL4 to the liver ,these enzymes will not be produced. Free radicals are highly reactive compounds with uneven number of electrons in their outermost orbit. This can react with cellular compounds like unsaturated fatty acids and can generate new free radicals which result in irreversible biochemical injury like membrane damage, apotosis and cell necrosis.

Antioxidants scavenge free radicals and stop the subsequent reactions hence protecting the macromolecules and cellular environment from toxicity and degeneration [Hong B.O. Shao et al, 2008].The oxygen consumption inherent in cell growth leads to the generation of series of reactive oxygen species [ROS].The ROS are molecules such as superoxide anion radicals and hydroxyl radicals[OH]. ROS may be very damaging attacking the lipids of cell membrane and DNA mutation which may further propagate the propagation of many diseases[Valontao et al 2002,Gulcin et al 2003]. Reactive oxygen species are continuously produced during normal Physiological events and are removed by antioxidants defence mechanism [Buyukokuroglu et al,2001]. Many results have shown that some of the cassia species have acquired antimicrobial substances and antioxidant activities.

1.1 Aims of the Research

The aim of this research is to find out hepatoproductive effects of sena tora leave extract on carbon tetrachloride induced toxicity.

Chapter Five

5.0 Discussion and Conclusion

5.1 Discussion

The liver is an organ of paramount importance which plays an essential role in the metabolism of foreign compound entering the body. Human beings are exposed to these compounds through environmental exposure, consumption of contaminated food or during exposure to chemical substances in the occupational environment in addition, human beings consume a lot of synthetic drugs during diseased conditions which are alien to body organs.
All these compounds produce a variety of toxic manifestations (Athor et al, 1997). Conventional drugs used in the treatment of liver diseases are often inadequate.

It is therefore necessary to search for alternative drugs for the treatment of liver diseases which has necessitated the radical shift to plant spacies (Rajesh et al, 2001).

The medical use of plants hepato protein like senna tora cannot be over emphasized. The choice of this plant for this research work is based on its various pharmacological activities properties.

The result of this study shows the potential susceptibility of exposed organisms including normal animals to hepatotoxic injury as a result of carbon tetrachloride intaxicatien through intraperitoneal injection.

The results however showed the role of methanolic extract of senna tora in protecting tissues and organs from peroxidative damage in CCL4 intoxicated rats.

The interest for oxidative stress in relation to the development of disease has gained large attention during the last decade. Lipid peroxidation is an example of oxidative injury that has been extensively studied. It is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. The reactive metabolites such as trilhloromethyl (CCL3) and tricholoromethy (peroxy) (CCL3O2) radicals emanate from CCL4 initiated peroxidation of membrane unsaturated fatty acids. The Lipid peroxidation of membrane seriously impairs its function and produces liver injury.

The control of Lipid peroxidation is of special significance in biology because of its particular importance in relation to membrane damage (Slater, 1984). The toxicity of CCL4 was first associated with the formation of the trichloromethyl radical (CCL3). Carbon tetra chloride was the first toxin from which it was shown that the injury it produces was largely or entirely mediated by free radicals.

Halliwell and Gucridge, 1999, Lipid peroxidation induced by CCL4 is a commonly used experimental animal model for studying oxidative injury in biological systems.

Cytochrorne P. 450 enzymes are believed to metabolise CCL4 to trichloromethyl radicals that can initiate peroxidation of unsaturated fatty acid and start chain reaction of Lipid peroxidation.

Studies have demonstrated that carbon tetrachloride – include hepatotoxicity like absorption can be influenced by dosing vehicles. The administration of CCL4 without using a corresponding standard dosing normally brings about experimental casualty to laboratory arrivals. The dosing vehicle used in this research work is corn oil. The mixing proportion of CCL4 to corn oil was in the ratio of 3:1. Corn oil has been found to decay markedly the absorption of CCl4 (Kim et al, 1990) as well as other halocarbons (Withey et al, 1983).

The results of the total cholesterol levels reduced significantly (P<0.05) in the group administered (I.P) the toxicant when compared with the negative control.

5.2 Conclusion

The results disclosed in this work suggest that carbon tetrachloride is a potential toxicant, which induced driver intoxication through lipid peroxidation process. The cytochrome P. 450 enzymes are believed to metabolize CCL4 to trichloromethyl radicals that can initiate peroxidation of unsaturated fatty acids.

My research work also suggest that the methorolic extract of the plant leaves of senna tora has the potential efficacy in protecting tissues and organs from peroxidative damage in carbon tetrachloride intoxicated rats. These results were achieved through the administration of the plant leaves extract appeared to confer healthy benefits on the test animals exposed to carbon tetrachloride intoxication. The administration (I.P) of low dose (500mg/kg body weight) of the extracts to the animals after exposing the animals to the toxicant for two days significantly increased the levels of serum cholesterol, but at high dose of the toxicant (2000mg/kg body weight) of the extract, the reverse was the case (reduced).

The finding support the reports that senna tora is used for the local treatment of liver ailments and is an important ingredient of pohyherbal formulations marketed for liver diseases. Senna tora extract can be both preventive and therapeutic. There are many other cofactors that may appear to modify the pharmacological vitamin E, A, C and glutathione.

5.3 Suggestion for Further Research

1. A study of doses lower than 500mg/kg body weight should be carried out to find out the appreciable hepatoprotectant effect of senna tora leaf extract.
2. The plant extract should be used in a more purified form.
3. The administration of the extract should follow either of the two stages.
   1. Before exposure to CCL4
   2. The simultaneous administration of both the toxicant and the extract.
4. Other antioxident’s research should be focused.

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