Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Biochemical and histopathological changes in Wistar Rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for Chronic Kidney Disease of Unknown Etiology (CKDu) in North Central Province (NCP) and Its comparison with Low disease prevalent Colombo, Sri Lanka(BioMed Central,, 2020) Thammitiyagodage, M.G.; de Silva, N.R.; Rathnayake, C.; Karunakaran, R.; Wgss, K.; Gunatillka, M.M.; Ekanayaka, N.; Galhena, B.P.; Thabrew, M.I.BACKGROUND: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water. METHOD: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method. RESULTS: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na+:Ca2+ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals. CONCLUSIONS: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats. KEYWORDS: BUN; CKDu; Microalbumin:creatinine; NCP.Item Protective effect of a polyherbal aqueous extract comprised of nigella sativa (Seeds), hemidesmus indicus (Roots), and smilax glabra (Rhizome) on bleomycin induced cytogenetic damage in human lymphocytes(Hindawi Pub. Co., 2017) Galhena, P.B.; Samarakoon, S.S.R.; Thabrew, M.I.; Paul, S.F.D.; Mani, C.This study was carried out to determine the chemoprotective potential of a polyherbal aqueous decoction comprised of Nigella sativa (seeds), Hemidesmus indicus (roots), and Smilax glabra (rhizome) against bleomycin induced cytogenetic damage in human lymphocytes. Isolated peripheral blood lymphocytes (PBLs) were exposed to bleomycin at a dose of 40 µg/mL for 2 hrs in the presence or absence of different doses of the decoction (100, 300, and 600 µg/mL). Modulatory effect of the decoction on bleomycin induced cytogenetic damage was evaluated by (a) degree of chromosomal aberrations (CA), (b) formation of micronuclei (MN), and (c) induction of γH2AX foci in lymphocytes exposed to bleomycin. Lymphocytes pretreated with the decoction showed that a significant reduction (p < 0.05) in bleomycin induced (a) stable and unstable chromosome aberrations (CA), (b) MN formation, and (c) formation of γH2AX foci, when compared to lymphocytes treated only with bleomycin. The decoction by itself did not induce any significant cytogenetic damage in PBLs. Overall results of the present study confirm that the decoction can attenuate the cytogenetic damage mediated by bleomycin in human PBLs.Item Hypoglycaemic and hypolipidaemic effects of an ethylacetate fraction of Artocarpus heterophyllus leaves(Intech, 2012) Chackrewarthy, S.; Thabrew, M.I.Item Extra - pancreatic actions of Trichosanthes cucumerina(Sri Lanka Association for the Advancement of Science, 2008) Arawwawala, L.D.A.M.; Thabrew, M.I.; Arambewela, L.S.R.Trichosanthes cucumerina Linn (Family: Cucurbitaceae), locally known as Dummella is commonly found in Asian countries including Sri Lanka. The aerial parts of T. cucumerina (T.C) are widely used in combination with other plants in the traditional medicinal systems as a remedy for fever, dropsy, acute bronchitis, boils, inflammation, skin diseases, jaundice, gastric lesions and diabetes. In Sri Lanka, the aerial parts of T.C are used as a remedy for diabetes. In a previous study we demonstrated that hot water extract (HWE) of T.C aerial parts can exert significant hypoglycemic activity in both normaglycemic and streptozotocine (STZ) induced diabetic rats. It was also shown that HWE had no effect on intestinal glucose absorption. A study was therefore, carried out to determine if extra - pancreatic effects were the main mechanisms by which the HWE exerts its hypoglycemic effect in rats. Extra - pancreatic effects were investigated by comparison of (a) Liver glycogen levels and (b)Triglyceride level in adipose tissue in normaglycemic and STZ - induced (by i.v. 50 mg/kg) diabetic rats that were orally treated with the HWE with those that did not receive the extract in the corresponding groups. Wistar rats (175 - 200 g body weight) were randomly divided in to 4 groups. Rats in Group 1 (n = 12; normal controls) were orally administered distilled water (1.0 ml/Kg), Group 2 (n = 12; normal test) received HWE (750 mg/kg of body weight), Group 3 (n = 7; diabetic control) received distilled water (1.0 ml/Kg) while group 4 (diabetic test) received HWE consecutively for 28 days. The dose of 750 mg/kg T.C was used because it exerted the maximum hypoglycemic effect in the previous study. Rats were kept fasting and, blood samples were collected from their tails at 14 days and 28 days post treatment and serum glucose levels determined. Subsequently, rats were sacrificed, livers and adipose tissues were harvested and subjected for estimation of glycogen levels and triglyceride levels respectively. In the diabetic rats, compared to the control group HWE significantly reduce the blood glucose levels at the end of 14 days and 28 days. The reduction in blood glucose was comparable to that produced by the antidiabetic drug, glibenclamide (0.6 mg/Kg). In normaglycemic rats HWE reduced the blood glucose levels at the end of 14 and 28 days. At the end of 28 days, it was found that in both normaglycemic and STZ - induced diabetic rats, there was a significant (P= 0.05) increase in the levels of liver glycogen (normaglycemic rats by 55.8 %; diabetic rats by 93.6 %) and adipose tissue triglyceride (normaglycemic rats by 14.3 %; diabetic rats by 16.7 %) in comparison with the respective controls that were not treated with HWE. It may be concluded that hypoglycemic effects demonstrated by T.C are mediated mainly via enhanced up take of blood glucose in to extra - pancreatic tissues. Financial assistance by National Science Foundation (Research Grant NSF/SCH/2005/13) is acknowleged.Item Hypoglycaemic and Hypolipidaemic effect of an ethylacetate fraction of Artocarpus heterophyllus (jak) leaves in streptozotocin induced diabetic rats(Sri Lanka Association for the Advancement of Science, 2009) Chackrewarthy, S.; Jayasekera, S.; Thabrew, M.I.; Weerasooriya, M.K.B.Previous investigations have shown that aqueous extracts of Artocarpus heterophyllus (jak) leaves (family Moraceae) can exert significant hypoglycaemic activity, and improve the glucose tolerance of healthy rats and humans, and newly diagnosed maturity onset diabetic patients. A preliminary study carried out by the authors with fractions separated from A. heterophyllus leaves showed that the ethylacetate fraction exerts the greatest hypoglycaemic activity in rats. The objective of the present study was to determine the effects of prolonged administration of ethylacetate fraction of A. heterophyllus leaves on serum glucose and lipid levels in streptozotocin induced diabetic rats since no reports are available on the effects of A. heterophyllus leaves on hyperlipidaemia associated with diabetes despite its clinical significance. Oral administration of the ethylacetate fraction (20 mg kg -1 bw) of A. heterophyllus leaves daily for five weeks significantly lowered serum glucose, cholesterol and triglyceride levels in streptozotocin induced diabetic rats. Compared to the control diabetic rats, the extract treated rats had 39% less serum glucose, 23% lower serum total cholesterol and 40% lower serum triglyceride levels and 11% higher body weight at the end of the fifth week. The percentage reductions in the serum parameters mediated by the test fraction were comparable with those produced by glibenclamide (57%, 32% and 42% reductions in serum glucose, cholesterol and triglycerides, respectively). The stimulation of insulin release by active principles in the ethylacetate fraction may be one of the mechanisms by which this fraction mediates its hypoglycaemic effect. It may be concluded that the ethylacetate fraction of A. heterophyllus leaves contain one or more hypoglycaemic and hypolipidaemic principles which have the potential to be developed further for the treatment of diabetes specifically associated with a hyperlipidaemic state.Item An investigation of toxicity of Trichosanthes cucumerina(Sri Lanka Association for the Advancement of Science, 2006) Arawwawala, L.D.A.M.; Thabrew, M.I.; Arambewela, L.S.R.Item Anti-Inflammatory activity is a possible mechanism by which the polyherbal formulation comprised of Nigella sativa (Seeds), Hemidesmus indicus (Root), and Smilax glabra (Rhizome) mediates its antihepatocarcinogenic effects(Hindawi Pub, 2012) Galhena, P.B.; Samarakoon, S.R.; Thabrew, M.I.; Weerasinghe, G.A.; Thammitiyagodage, M.G.; Ratnasooriya, W.; Tennekoon, K.H.The present study investigated the anti-inflammatory effects of a polyherbal decoction comprised of Nigella sativa, Hemidesmus indicus, and Smilax glabra in order to justify its claimed antihepatocarcinogenic activity. Activation of hepatic nuclear factor-kappa B (NF-κB), IκB kinase (IKK α/β) proteins, and TNFα and IL-6 expression was investigated in diethylnitrosamine- (DEN-) induced C3H mice-bearing early hepatocarcinogenic changes. Acute phase inflammatory response was evaluated by carrageenan-induced rat paw edema formation. Anti-inflammatory mechanisms were also assessed by determining effect on (a) membrane stabilization, (b) nitric oxide (NO) inhibitory activity, and (c) inhibition of leukocyte migration. A significant inhibition of the paw edema formation was observed in healthy rats as well as in rats bearing early hepatocarcinogenic changes with oral administration of the decoction. As with the positive control, indomethacin (10 mg/kg b.w.) the inhibitory effect was pronounced at 3rd and 4th h after carrageenan injection. A notable IKK α/β mediated hepatic NF-κB inactivation was associated with a significant hepatic TNFα down regulation among mice-bearing hepatocarcinogenic changes subjected to decoction treatment. Inhibition of NO production, leukocyte migration, and membrane stabilization are possible mechanisms by which anti-inflammatory effect is mediated by the decoction. Overall findings imply that anti-inflammatory activity couldItem A Long-term investigation of the anti-hepatocarcinogenic potential of an indigenous medicine comprised of Nigella sativa, Hemidesmus indicus and Smilax glabra(BioMed Central, 2006) Iddamaldeniya, S.S.; Thabrew, M.I.; Wickramasinghe, S.M.D.N.; Ratnatunga, N.; Thammitiyagodage, M.G.BACKGROUND: A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root bark and Smilax glabra rhizome is being recommended for cancer patients by a family of traditional medical practitioners of Sri Lanka. Previous investigations have demonstrated that a short term (10 weeks) treatment with the decoction can significantly inhibit diethylnitrosamine (DEN) mediated expression of Glutathione S-transferase P form (GST-P) in rat liver. The objective of the present investigation was to determine whether long term (16 months) treatment with the decoction would be successful in inhibiting in rat livers, not only DEN- mediated expression of GST-P, but also the carcinogen mediated development of overt tumours (OT) or histopathological changes leading to tumour development (HT). METHODS: Thirty-six male Wistar rats were divided into 3 groups of 12 each. Groups 1 and 2 were injected intraperitoneally (i.p) with DEN (200 mg/kg) while group 3 was injected normal saline (NS). Twenty-four hours later, decoction (DC; 6 g/kg body weight/day) was orally administered to group 1 rats, while groups 2 and 3 (DEN-control and normal control) were given distilled water (DW). Treatment with DC or DW continued for 16 months. At the end of the 9th month and 16th months (study 1 and study 2 respectively), six rats from each group were sacrificed, and livers observed for OT or HT, both visually and by subjecting liver sections to staining with Haemotoxylin and Eosin (H & E), Sweet's Silver stain (for reticulin fibers), Periodic Acid Schiff (PAS) staining (for glycogen), and immunohistochemical staining (for GST-P). RESULTS: At the end of 9 months (study 1) a hepatocellular adenoma (HA) developed in one of the rats in the DEN + DW treated group (group 2). At the end of 16 months (study 2), livers of all rats of group 2 developed OT and HT. Large areas of GST-P positive foci were also observed. No OT, HT or GST-P positive foci were detected in any of the other groups. CONCLUSION: Protection against DEN-mediated carcinogenic changes in rat liver can be achieved by long term treatment with the DC comprised of N. sativa seeds, S. glabra rhizome and H. indicus root bark.Item Protection against diethylnitrosamine induced hepatocarcinogenecity by an indigenous herbal remedy comprised of Nigella sativa, Hemidesmus indicus and Simlax glabra: a preliminary study(Medknow Publications, 2003) Iddamaldeniya, S.S.; Wickremasinghe, S.M.D.N.; Thabrew, M.I.; Ranatunge, N.; Tammitiyagodage, M.G.BBACKGROUND: A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used to treat cancer patients in Sri Lanka. However, the anti-carcinogenic properties of this decoction have not been experimentally confirmed. The purpose of this study was to determine whether the above decoction could protect against chemically induce hepatocarcinogenesis. METHODS: The effects of this decoction on diethylnitrosamine (DEN) induced hepatocarcinogenesis were examined in male Wistar rats using the medium term bioassay system of Ito, based on a 2-step model of hepatocarcinogenesis. Rats were randomly divided into 6 groups of 10 each. Groups 1 to 4 were injected with DEN (200 mg/kg) to initiate carcinogenesis. Twenty-four hours later groups 1 and 2 were administered the decoction at 4 g/kg body weight/day (dose 1) and 6 g/kg body weight/day (dose 2), respectively. Group 3 and group 4 were given distilled water instead of the decoction and a suspension of garlic powder (20 g/kg body weight/day) in distilled water (positive control), respectively. Group 5 and 6 were injected with normal saline and twenty-four hours later group 5 was given distilled water (normal control) while group 6 was given decoction dose 2 (decoction control). Oral feeding continued for two weeks after which all rats were subjected to 2/3 partial hepatectomy to promote carcinogenesis. Oral feeding continued for eight more weeks. At the end of the 10th week, rats were sacrificed and samples of livers taken for immunohistochemical studies. Carcinogenic potential was scored by comparing the number, area and staining intensity of glutathione S-transferase placental form (GST-P) positive foci and the number of cells/cm2 of the positive foci in the livers of the six groups of rats. RESULTS: The number and area of DEN-mediated GST-P positive foci, number of cells/cm2 of foci and staining intensity of the foci were significantly (P > 0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1. CONCLUSION: Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesiss