Browsing by Author "Mudduwa, L.K.B."

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In vitro and in vivo antioxidant potential and phytochemical constituents of Barleria prionitis Linn. extracts
(Faculty of Science, University of Kelaniya, Sri Lanka, 2020) Amarasiri, A.M.S.S.; Attanayake, A.P.; Arawwawala, L.D.A.M.; Jayatilaka, K.A.P.W.; Mudduwa, L.K.B.
Medicinal plants are natural sources of antioxidants. The use of antioxidants in the management of chronic diseases is an emerging therapeutic approach in the present era. Administration of several antioxidant compounds has demonstrated protective effects against nephrotoxicity induced by the anticancer drug; adriamycin in preclinical studies. Barleria prionitis Linn. (Family; Acanthaceae, common name: Katukarandu), is a medicinal plant with various therapeutic applications in kidney related diseases in Sri Lankan traditional medicine system. It is hypothesized that, nephroprotective effects of the plant is via its antioxidant potential. Herein, we aimed to assess the antioxidant potential of selected extracts of B. prionitis whole plant in adriamycin induced nephrotoxicity in vivo, to determine the total antioxidant activity in vitro and to identify the phytoconstituents in selected extracts. The hexane, ethyl acetate, butanol and aqueous extracts of B. prionitis were prepared by sequential Soxhlet extraction. Plant extracts were administered to adriamycin induced (5 mg/kg, ip) nephrotoxic Wistar rats (n = 6) at the human equivalent therapeutic dose (25 mg/kg, 80 mg/kg, 70 mg/kg, 120 mg/kg respectively), and standard drug fosinopril sodium (0.09 mg/kg) for 28 consecutive days as a daily single dose. The kidney tissues were excised from the sacrificed rats on the 28th day. The total antioxidant level and activity of glutathione reductase (EC 1.6.4.2) and glutathione peroxidase (EC 1.11.1.9) were estimated in the kidney homogenates of all experimental rats. Results were analyzed statistically by one-way ANOVA and Dunnett post hoc test and compared against the adriamycin induced nephrotoxic control group. The in vitro total antioxidant activity was determined by 2, 2’- diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. The qualitative screening of phytoconstituents was carried out for the presence of phenolic compounds, flavonoids, tannins, terpenoids, steroid glycosides, saponins, coumarins, and alkaloids using standard procedures. A significant increase in the total antioxidant concentration (62%, 71%, 59%, 58%) and in the activity of glutathione peroxidase (439%, 298%, 286%, 234%) was perceived following the treatment with hexane, ethyl acetate, butanol and aqueous extracts of B. prionitis respectively (p < 0.05). A significant increase in the concentration of glutathione reductase was noted only with the ethyl acetate (32.58 ± 2.55 U/L), butanol (27.66 ± 1.86 U/L) and with the aqueous (26.72 ± 1.57 U/L) extracts. No significant improvement in the activity of antioxidant enzymes was observed in fosinopril treated rats (p > 0.05). The in vitro total antioxidant capacity was deviated in the descending order of butanol (IC50; 163.1 ± 2.1 μg/mL), aqueous (IC50; 297.0 ± 2.3 μg/mL), ethyl acetate (IC50; 775.6 ± 10.8 μg/mL), and hexane (IC50; 961.7 ± 13.9 μg/mL) extracts of B. prionitis respectively. Phenolic compounds, flavonoids, tannins, steroid glycosides, terpenoids and saponins were present in the selected extracts at varying extents. The results revealed that selected extracts of B. prionitis improved the antioxidant enzyme levels in adriamycin induced nephrotoxicity in Wistar rats. Further, the selected plant extracts showed relatively high antioxidant activity in vitro. The phytoconstituents present in the B. prionitis extracts may attribute to its antioxidant potential.
Nottingham grade 2 breast cancer; is it a true prognostic category?
(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Peiris, H.H.; Mudduwa, L.K.B.; Thalagala, N.I.; Jayatilake, K.A.P.W.
BACKGROUND: Nottingham grade (NG) is a well-recognized prognostic factor derived by adding scores (1-3) given for three histological features of breast cancer (BC). NG is assigned according to the final score (NG1=score 3-5, NG2=score 6-7, NG3=score 8-9) where NG1 has the best and NG3 has the worst prognosis. OBJECTIVE: To assess whether the NG2 entails only patients with a similar prognosis. METHODS: Data were collected from all NG2 BC patients who had sought the services of our unit from 2006 to 2012. Grading was done by a single investigator. Patients were divided into two groups according to the score assigned in grading (6 and 7) and followed up with a mean follow-up time of 45 (SD=23) months. Clinico-pathological features were compared using chi-square test. Kaplan-Meier model with log-rank test was used for survival analysis. RESULTS: The study included 352 NG2 BC patients (score 6=195; score 7=157) with a mean age of 52 (SD=11) years. Majority of the patients with score 6 had ER/PR positive tumours (p=0.007 and 0.029) whereas score 7 patients had Her 2 positive tumours (p=0.002). There was a significant survival difference between the patients who had scores 6 and 7 (breast cancer specific survival p=0.007; recurrence free survival p=0.019). There was no survival difference between the patients with NG1 and score 6 and NG3 and score 7 (p>0.05). CONCLUSIONS: NG2 comprises two subsets of patients with a significant survival difference. Their prognosis is more in line with the preceding/subsequent grade than the same grade, probably due to the difference in ER/PR and Her 2 expression.
Role of Cancer antigen 15.3 in the pre-operative assessment of primary breast cancer
(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2016) Peiris, H.H.; Mudduwa, L.K.B.; Wijeratne, W.M.D.G.B.; Liyanage, T.G.; Liyanage, N.C.; Gunasekara, S.N.; Kaushalya, M.H.A.
BACKGROUND: Cancer antigen (CA) 15.3 is the most commonly used tumour marker in predicting recurrence of breast cancer. The role of pre-operative CA 15.3 in the assessment of breast cancer has not been substantiated yet. OBJECTIVE: To determine the role of CA 15.3 in the pre-operative assessment of breast cancer patients METHODS: All patients who were diagnosed of primary breast cancer and underwent surgery at a tertiary-care hospital from April 2014 to October 2015 were enrolled. Serum level of CA 15.3 was assessed on a pre-operative blood sample by ELISA and ≥30 U/ml was considered as the cut off as defined by the manufacturer’s literature. The association of CA 15.3 levels with the clinico-pathological parameters was analyzed with chi-square test. RESULTS: Of the 150 patients (mean age 56.83 [SD=13.39] years) enrolled, majority (85.6%) had grade 2/3 tumours with lymph node metastasis (58.2%) at the time of presentation. None had distant metastasis. Elevated pre-operative serum level of CA 15.3 was detected in 34% of patients who had more estrogen receptor negative(43.13%), progesterone receptor negative (50.98%) and triple negative(29.1%) tumours compared to those without elevated pre-operative CA 15.3 (p=0.017,0.036 and 0.001 respectively). There was no association with other clinico-pathological features. CONCLUSIONS: Pre-operative serum level of CA15.3 is elevated only in one third of breast cancer patients. Elevated pre-operative CA 15.3 has a prognostic value as it is elevated mostly in the hormone receptor negative and triple negative breast cancers predicting a poor prognosis.
Therapeutic potential of Cinnamomum zeylanicum Blum aqueous bark extract on doxorubicin induced cardiotoxicity in Wistar rats
(Faculty of Science, University of Kelaniya, Sri Lanka, 2020) Sandamali, J.A.N.; Hewawasam, R.P.; Jayatilaka, K.A.P.W.; Mudduwa, L.K.B.
The effectiveness of doxorubicin as an anti-cancer agent is hampered by its’ life-threatening cardiotoxicity induced by oxidative-stress. As Cinnamomum zeylanicum Blum has proven antioxidant activity, the objective of this study was to find out the therapeutic potential of aqueous Cinnamomum bark extract against cardiotoxicity induced by doxorubicin in Wistar rats. Sample size of the study group was determined and an equal number of male and female Wistar rats were randomly selected into five groups. Group 1: normal-control (distilled water for 14 days, normal saline (10 mL/kg) on 11th day); group 2: plant control (2.0 g/kg of freeze dried plant extract for 14 days, normal saline (10 mL/kg); group 3: doxorubicin control (distilled water for 14 days, doxorubicin (18 mg/kg) on 11th day); group 4: freeze dried plant extract (2.0 g/kg) for 14 days, doxorubicin (18 mg/kg) on 11th day; group 5: distilled water for 14 days, dexrazoxane (180 mg/kg) 0.5 h before doxorubicin (18 mg/kg). Animals were sacrificed on the 15th day, blood was drawn for biochemical analysis and heart tissues were collected for estimation of antioxidant parameters and histological assessment of tissue damage. A significant (p ˂ 0.05) elevation in cardiac biomarkers including cardiac troponin I, AST, LDH and NT-proBNP activity were observed in doxorubicin-control group compared to the normal-control. Pretreatment with Cinnamomum bark extract in the doxorubicin treated rats showed a significant reduction (p ˂ 0.05) in above cardiac biomarkers compared to the doxorubicin-control. A significant reduction (p ˂ 0.05) in reduced glutathione, glutathione peroxidase and glutathione reductase was observed in the doxorubicin control group (Group 3) compared to the normal-control. Total antioxidant capacity as well as superoxide dismutase and catalase activity were markedly reduced (p < 0.05) in the doxorubicin control group. However, pretreatment with Cinnamomum extract was capable of significantly increasing (p ˂ 0.05) all of the above antioxidant parameters compared to the rat group which was treated with doxorubicin alone. A significant increase (p ˂ 0.05) in malondialdehyde concentration, which measures the lipid peroxidation and myeloperoxidase activity, which measures the extent of inflammation was observed in the doxorubicin-control compared to the normal-control. The plant-treated group showed a significant decrease (p ˂ 0.05) in malondialdehyde concentration and myeloperoxidase activity compared to the doxorubicincontrol. Histological assessment of tissue damage was scored according to a scale developed by the authors and doxorubicin-treated group showed a significant damage to the myocardium showing the highest score among the five groups. Plant-treated group showed only a minor degree of damage and showed a significant reduction in the score compared to the doxorubicin control. In conclusion, C. zeylanicum Blum bark extract has the potential to significantly reduce doxorubicin induced cardiotoxicity in Wistar rats.