THE EFFECT OF ETHANOL EXTRACT OF DENNETTIA TRIPETALA ON LIVER AND KIDNEY ANTIOXIDANT ENZYME ACTIVITY AND MALONDIALDEHYDE CONCENTRATION OF ALBINO WISTAR RATS EXPOSED TO CCl4
The effect of ethanol extract of Dennettia Tripetala on rats exposed to carbon tetrachloride was investigated. Ethanol extract of the plant was prepared using standard procedure. Sets of 30 female wistar albino rats were divided into 6 groups containing five animals each and were treated orally with increasing doses of ethanol extract of Dennettia Tripetala for two weeks. CCl4 was diluted with olive oil in a 1:1 ratio and administered once by oral route at the end of the extract administration. Results from the study showed non- significant decreases in the levels of catalase and SOD activities (P>0.05) in the CCl4 group compared to the control. The extract treatment however produced a higher activity for the antioxidant enzymes compared to the CCl4 treated groups. The results also showed increased levels of MDA concentration (P<0.05) in the CCl4 group whereas extract treated rats showed lower concentrations of MDA. The overall results suggests that the ethanolic extract of Dennettia tripetala may have moderate hepatoprotective effect in the CCl4 induced rats.
Natural plant products and their derivatives represent more than 50% of all the drugs in clinical use in the world (Ben-Eric, 2002). Dennettia Tripetala also known as pepper fruit tree is a well-known Nigerian spicy medicinal plant. It is found in the tropical rainforest region of Nigeria and sometimes in Savanna areas (Okwu et al., 2005). It is locally called “Nkarika” by the Efiks of Calabar. The young leaves and fruits have distinctive spicy taste. The mature fruits constitute the main edible portions. Some communities in parts of Southern Nigeria also utilize the leaves and roots, in addition to the fruits for medicinal purpose. Dennettiatripetal Has been found to contain lots of minerals, vitamins, alkaloids and trace elements which are of medicinal importance. It was also indicated that the rich presence of essential oil (oleoresins) determines the aromatic flavoring, coloring and pungent properties of pepper fruits. (Nwaoguet al., 2007) investigated phytochemical content of Dennettia Tripetala and detected the presence of saponins, flavonoids, tannins and cyanogenic glycosides. The intake of flavonoids in any fruit and vegetable tends to decrease cancer risk (Neuhouser, 2004; Grafet al., 2005). Flavonoid contributes to the color of plants, their fruits and flowers. The use of medicinal plants in traditional medicine is not intended in any way to replace modern medical science but rather an aid in conventional therapy (Ben-Eric, 2002).
Carbon tetrachloride (CCl4) is an industrial chemical that does not occur naturally. Most of the carbon tetrachloride produced is used in the production of chlorofluorocarbons (CFCs) and other chlorinated hydrocarbons. It was once used widely as a solvent, cleaner and degreaser, both for industrial and home use. Today, the scientific database on the effects of haloalkanes is so vast that it is no longer employed for such purposes although it is used as a model of experimental liver injury (Weber et al., 2003).
CCl4 is a well-known hepato- and neurotoxicant (Thrall et al., 2000; Ogeturket al., 2005), and proves highly useful as an experimental model for the study of certain hepatotoxic effects (Muriel et al., 2003; Moreno and Muriel, 2006). CCl4-induced toxicity, depending on dose and duration of exposure, covers a variety of effects. At low doses, transient effects prevail, such as loss of Ca2+ homeostasis, lipid peroxidation, release of noxious or beneficial cytokines (Kyung-Hyun et al., 2006; Muriel, 2007) and apoptotic events followed by regeneration. Other effects, with higher doses or longer exposure, are more serious and develop over a long period of time, such as fatty degeneration, fibrosis, cirrhosis and even cancer (Weber et al., 2003). In addition, acute intoxication with CCl4 at high doses, when the hepatocellular necrosis exceeds the regenerative capacity of the liver, fatal liver failure will ensue. Extreme doses of CCl4 result in nonspecific solvent toxicity, including central nervous system depression and respiratory failure and death.
This study aims at investigating the effect of ethanol extract of Dennettia Tripetala On liver and kidney antioxidant enzyme activity and malondialdehyde concentration of rats exposed to CCl4.
1.1 LITERATURE REVIEW
1.1.0 THE LIVER
The liver is the largest organ of the human body weighing approximately 1500 g, and is located in the upper right corner of the abdomen on top of the stomach, right kidney and intestines and beneath the diaphragm. The liver performs more than 500 vital metabolic functions (Naruseet al., 2007). It is involved in the synthesis of products like glucose derived from glycogenesis, plasma proteins, clotting factors and urea that are released into the bloodstream. It regulates blood levels of amino acids.
Liver parenchyma serves as a storage organ for several products like glycogen, fat and fat soluble vitamins. It is also involved in the production of a substance called bile that is excreted to the intestinal tract. Bile aids in the removal of toxic substances and serves as a filter that separates out harmful substances from the bloodstream and excretes them (Saukonenet al., 2006). An excess of chemicals hinders the production of bile thus leading to the body’s inability to flush out the chemicals through waste.
Smooth endoplasmic reticulum of the liver is the principal ‘metabolic clearing house’ for both endogenous chemicals like cholesterol, steroid hormones, fatty acids and proteins, and exogenous substances like drugs and alcohol. The central role played by liver in the clearance and transformation of chemicals exposes it to toxic injury (Saukonenet al., 2006).
126.96.36.199 FUNCTIONS OF THE LIVER
The liver has three main functions: storage, metabolism, and biosynthesis. Glucose is converted to glycogen and stored; when needed for energy, it is converted back to glucose. Cholesterol uptake also occurs in the liver. Fat, fat-soluble vitamins and other nutrients are also stored in the liver. Fatty acids are metabolized and converted to lipids, which are then conjugated with proteins synthesized in the liver and released into blood stream as lipoproteins. Numerous functional proteins such as, enzymes and blood-coagulating factors are also synthesized by the liver. In addition, the liver, which contains numerous xenobiotic metabolizing enzymes, is the main site of xenobiotic metabolism (Hogson and Levi, 2004).
188.8.131.52 BIOTRANSFORMATION OF HEPATOTOXICANTS
Liver plays a central role in biotransformation and disposal of xenobiotics.
The close association of liver with the small intestine and the systemic circulation enables it to maximize the processing of absorbed nutrients and minimize exposure of the body to toxins and foreign chemicals. The liver may be exposed to large concentrations of exogenous substances and their metabolites. Metabolism of exogenous compounds can modulate the properties of hepatotoxicity by either increasing its toxicity (intoxication or metabolic activation) or decreasing its toxicity (detoxification).
Most of the foreign substances are lipophilic thus enabling them to cross the membranes of intestinal cells. They are rendered more hydrophilic by biochemical processes in the hepatocyte, yielding water-soluble products that are exported into plasma or bile by transport proteins located on the hepatocyte membrane and subsequently excreted by the kidney or gastrointestinal tract (Totsmannet al., 2008).
The hepatic biotransformation involves Phase I and Phase II reactions. Phase I involves oxidative, reductive, dehydroxylation and demethylation pathways, primarily by way of the cytochrome P-450 enzyme system located in the endoplasmic reticulum, which is the most important family of metabolizing enzymes in the liver. The endoplasmic reticulum also contains a NADPH-dependent mixed function oxidase system, the flavin-containing monooxygenases, which oxidizes amines and sulphur compounds.
Phase I reactions often produce toxic intermediates which are rendered non-toxic by phase II reactions. Phase II reactions involve the conjugation of chemicals with hydrophilic moieties such as glucuronide, sulfate or amino acids and lead to the formation of more water-soluble metabolite which can be excreted easily. Another Phase II reaction involves glutathione which can covalently bind to toxic intermediates by glutathione-S- transferase. As a result, these reactions are usually considered detoxification pathways. However, this phase can also lead to the formation of unstable precursors to reactive species that can cause hepatotoxicity.
The activities of enzymes are influenced by various endogenous factors and exogenous drugs or chemicals (Lee and Boyer, 2000). Many substances can influence the cytochrome P450 enzyme mechanism. Such substances can serve either as inhibitors or inducers. Enzyme inhibitors act immediately by blocking the metabolic activity of one or several cytochrome P450 enzymes. Enzyme inducers act slowly and increase cytochrome P450 activity by increasing its synthesis (Lynch and Price, 2007).
The kidneys are bean-shaped organs that serve several essential regulatory roles in vertebrates. They remove excess organic molecules from the blood and their best known function is the removal of waste products of metabolism. They serve homeostatic functions such as the regulation of electrolytes, maintenance of acid-base balance, and regulation of blood pressure (via maintaining the salt and water balance). In producing urine, the kidneys excrete wastes such as urea and ammonium. They are responsible for the reabsorption of water, glucose, and amino acids. They also produce hormones like calcitriol and erythropoietin.
1.2.1 FUNCTIONS OF THE KIDNEY
Many of the kidney’s functions are accomplished by relatively simple mechanisms of filtration, reabsorption, and secretion, which take place in the nephron. Filtration, which takes place at the renal corpuscle, is the process by which cells and large proteins are filtered from the blood to make an ultrafiltrate that eventually becomes urine. The kidney generates 180 litres of filtrate a day, while reabsorbing a large percentage allowing for the generation of only approximately 2 litres of urine. Reabsorption is the transport of molecules from this ultrafiltrate into the blood. Secretion is the reverse process, in which molecules are transported in the opposite direction, from blood to the urine.(Bard et al., 2003).
184.108.40.206 Excretion of wastes