ANTI-ULCERATIVE EFFECT OF AQUEOUS EXTRACT OF CUCUMIS MELO ON NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) INDUCED GASTRIC ULCERATION IN MALE WISTAR RATS
ABSTRACT
Ibuprofen, a strong analgesic and an anti-inflammatory drug used over a long period caused side effects such as peptic ulcer and constipation. Honeydew melon has been shown to possess antisecretory, antiulcer and angiogenic. Hence, this study investigated the anti-ulcer effect of aqueous extract of honeydew melon on ibuprofen induced gastric ulcer in male Wistar rats.
Wistar rats (n=35,150-200g) were randomly divided into seven groups. They were treated as follows; I (control- distilled water),II- ibuprofen induced ulcer untreated (400mg/kg ibuprofen, p.o),III(ibuprofen induced ulcer + misoprostol (200μg/kg),IV-VII induced with ibuprofen and treated with 25%, 50%, 75%, and 100%aqueous extract of honeydew melon (HDM) for 3 weeks prior to gastric ulcer induction, respectively. Gastric secretion was measured by titrimetric method, and the ulcer score was measured. Assessment of activities of Superoxide Dismutase (SOD), Catalase, and protein level, Malondialdehyde, H+/K+ ATPase were determined by spectrophotometry. Prostaglandins synthesis was measured using Enzyme linked immunosorbent assay kit. Data were expressed as Mean + SEM, analyzed using one-way ANOVA, with P<0.05
The total gastric acidity was significantly increased in group II (2.80±0.12) compared to group I (0.50± 0.00mEq/L),P<0.001, pretreatment with aqueous extract of HDM significantly decrease the total gastric acidity in IV, V, VII compared to group II, P<0.05. The ulcer score and index was significantly decrease in all the treatment compared to group II, P<0.05. The percentage inhibition increased significantly in all treatment groups compared to the group II. The Lipid peroxidation (MDA) increase significantly in the group II (untreated compared to the treated groups, p<0.05. The protein level and activities of the catalase, superoxide dismutase significantly increased in treatment groups compared with group II, P<0.05. Prostaglandin E2 expression increased significantly in the all treatment groups with much increase in VII, compared with other groups, p<0.05. Activities of H+/K+ ATPase was significantly decreased in the treatment groups compared to the group II(P<0.05).In conclusion, the findings from this study suggests that extract of HDM possess antiulcer properties due its ability to increase antioxidant activities, synthesis of prostaglandins and reduce the activities of H+/K+ATPase .
Keywords: honeydew melon, total gastric acidity, prostaglandin E2, antioxidants, H+/K+ATPase
Word count = 300.
CHAPTER ONE
1.0 INTRODUCTION
The gastrointestinal tract (GIT) primary function is to serve as a portal whereby nutrients and water can be absorbed into the body (Barret and Barman, 2016). The gastrointestinal tract starts from the mouth to the anus, its length is about 30 feet in adult (Zimmerman, 2016), and its organs includes the mouth, esophagus, stomach, small and large intestines, anus. It is a specialized system that provides the body with nutrients and water by performing the following functions, digestions, transportation, absorption , elimination of waste products(Cheng et al., 2014).
There are several diseased conditions affecting the GIT which affect the overall health of the body.
The common diseases of the GIT includes celiac diseases, Crohn’s disease or inflammatory bowel diseases , Zollinger Ellison disease, Constipation , Diarrhea, tropical sprue ,achalasia, gastroesophageal reflux diseases ( Falko, 2012).
Other digestive disorders include; Irritable bowel syndrome, lactose intolerance, malabsorption syndromes, peptic ulcer, ulcerative colitis, vomiting.
Peptic ulcer is a discontinuation or abrasion of the stomach/intestinal mucosa or upper part of the small intestine by digestive juice or intestinal secretion. It is a combination of diverse disorder which is evident as erosion or sore on the gastrointestinal mucosa lining. It usually occur in the fundic part of the stomach or lower esophageal sphincter or the upper part of duodenum (Hall and Guyton, 2013). It is common and the percentage distribution is global. Peptic ulcer arises as a result of imbalance between the offensive and protective factors (Malik et al., 2019). The offensive factors includes acid, pepsin, bile acids, depressed secretion of prostaglandins, reduced blood flow to gastric mucosa, impeded mucosal growth and cell proliferation, and alteration of gastric motility(Qureshi, 2015).
The gastric protective factors include prostaglandin secretion, bicarbonate secretion, expression of growth factors, etc (Silva and Sousa, 2011).Several factors are involved in pathogenesis of peptic ulcer such as helicobacter pylori, use of non-steroidal anti-inflammatory drugs, life style. Approximately 70–90% of ulcers are said to be related to Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach.
From studies, the importance of gastric H+/K+ -ATPase in the parietal cell of the gastric mucosa cannot be exempted, as it controls the movement transport of HCl through membrane by H for K exchange catalyzed by ATP driven phosphorylation/dephosphorylation (Shin et al., 2009). Its expression during gastric injury cannot be over emphasized. The inhibition of this enzyme has been a therapeutic index during healing of gastric ulceration or injury
From studies, it has also been found that disequilibrium between oxidant and antioxidants contributes to inflammation and this can lead to ulceration of the gastric mucosa (Kisaoglu et al., 2013). Increase in expression of Reactive Oxygen Species has been one of the major culprit that directly results in oxidative damage, including lipid peroxidation, protein oxidation, and DNA damage, which can lead to cell death. In the illness state, oxidative stress of the stomach may occur and result in an elevation of mucosal lipid peroxide that are generated from the reaction of oxyradicals and cellular poly unsaturated fatty acid, while GSH may act to prevent this aggressive action that can damage gastric mucosal cells. Malondialdehyde (MDA) is an end product resulting from peroxidation of polyunsaturated fatty acids and related esters within cell membranes, and the measurement of this substance represents a suitable index of oxidative tissue damage. Other antioxidants such as Superoxide dismutase, catalase function to prevent the buildup of free radicals or reactive species in cells. They act very quickly to deactivate chain reactions that might lead to production of free radicals (Ighadaro et al., 2018). The cytoprotective action of prostaglandins is as a result of its complex ability to stimulate mucosal mucus and bicarbonate secretion, to increase mucosal blood flow and sulfhydryl compounds and limit back diffusion of acid into the epithelium in the stomach (Tarnawski et al., 1985,Farhadi et al.,2003;Kato et al.,2005).
Numerous studies have demonstrated that herbal medicines can effectively treat gastric ulcer in humans and animals via divergent mechanisms (Bi et al., 2014). Studies have demonstrated that the efficacy of herbal medicines is comparable or even superior to that of drugs and that herbal medicines display less adverse effects (Bi et al., 2014). Researches have proved that flavonoids or bioflavonoids which are naturally occurring compounds in fruits and vegetables may be an effective additional treatment for stomach ulcers (Krans and Carey 2019). Other naturally occurring ulcer remedies include; probiotics, honey, garlic, cranberry etc.
Cucmis melo otherwise known as honeydew melon is a delicious oval shaped fruit with vast nutritional values. (Zhang et al., 2020). Honeydew melon like most melons is rich in fiber, vitamins, mineral sand plant phenols. Consumption of polyphenol rich plants may decrease inflammation and oxidative damages (Shoemaker, 2019).
1.1. STATEMENT OF PROBLEM
Ibuprofen is a strong analgesic and an anti-inflammatory drug. Due to its availability in the market, ibuprofen has become very common painkiller. It is often consumed by different individuals to alleviate pains, fever, inflammations, cramps etc. (Ngo and Bajaj 2019).The main side effects of ibuprofen especially when used over a long period of time include gastric ulcer, duodenal ulcer and indigestion etc. (Liu et al., 2016). Over the years, the rate at which ibuprofen is being administered increased steadily due to its important as strong analgesics.
Cucumis melo or honeydew melon has been found to be effective in treatment of experimentally induced ulceration by indomethacin (Adebayo-Gege et al., 2019). It was reported Cucumis melo possess antisecretory properties and possesses angiogenic properties by increasing expression of CD31 (Platelette endothelial cell adhesion molecule) which should be responsible for its antiulcer properties. NSAIDs used in large doses over a long period of time cause ulcer by interfering with the ability of the stomach cells to protect themselves from aggressive factors(Rogoveanu et al., 2015).NSAIDs cause ulcers by inhibiting cyclooxygenase-1, a key enzyme in the synthesis of prostaglandins (Drini, 2017).
HYPOTHESIS 0: Honeydew melon will prevent pathogenesis of ibuprofen induced gastric injury.
HYPOTHESIS 1: Honeydew melon will not prevent pathogenesis of ibuprofen induced gastric
injury.
1.1.1. AIM
The aim of this study was to investigate the antiulcer properties of aqueous extract of honeydew melon on ibuprofen induced gastric ulceration in male Wistar rats
1.1.2. OBJECTIVES
Study its anti-ulcerative effects on ibuprofen induced gastric ulceration by
- Evaluating its effect on total gastric acidity, Ulcer score , ulcer index
- Assessing the Percentage inhibition, oxidative stress and antioxidant status
- Assessing its regulatory role on the H+/K+-ATPase and Prostaglandins
ANTI-ULCERATIVE EFFECT OF AQUEOUS EXTRACT OF CUCUMIS MELO ON NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) INDUCED GASTRIC ULCERATION IN MALE WISTAR RATS