http://hdl.handle.net/123456789/142 2026-04-08T22:53:58Z http://hdl.handle.net/123456789/342 CARDIAC AND RENAL PROTECTIVE EFFECTS OF Andrographis paniculata LEAF EXTRACT IN MALE WISTAR RATS ADEOYE, BISI OLAJUMOKE Cardiovascular and renal diseases are one of the leading causes of morbidity and mortality in humans. However, conventional drugs used for treatment of these diseases have adverse effects and are not readily affordable. Botanicals such as Andrographis paniculata rich in antioxidants are promising alternatives. Hence, protective effect of Ethanol Leaf Extract of Andrographis paniculata (EEAP) in isoproterenol-induced myocardial infarction and cisplatin-induced renal injury in rats were investigated. Fresh leaves of Andrographis paniculata (Voucher No:UIH-2846) was extracted using ethanol. Cardioprotective effects of EEAP were evaluated in male wistar rats (n=49; 100-160 g) equally divided into seven groups. Group A (control) was administered normal saline, group B; isoproterenol at 85 mg/kg, groups C, D, E and F were pretreated with enalapril 10 mg/kg, EEAP 100, 200 or 400 mg/kg, respectively, for 7 days and thereafter administered isoproterenol on days 8 and 9. Group G was administered isoproterenol on days 1 and 2, thereafter treated with 200 mg/kg of EEAP for 7 days. Administration of isoproterenol was subcutaneous, while enalapril and EEAP were oral. Electrocardiogram and blood pressure (BP) parameters were done on day 10 and animals were sacrificed 24 hours later. Cardiac tissues were assayed for markers of oxidative stress (malondialdehyde, H2O2), and antioxidant defence system (SOD, GPx, GST). Histopathology and immunohistochemistry (Cardiac troponin-I, Creactive protein, Interleukin-10) were evaluated. Renoprotective effects of EEAP were evaluated in another 49 wistar rats (100-150 g) divided into seven equal groups. Group A1 (control), group B1 was treated with cisplatin (10 mg/kg) only on day 8, groups C1 and D1 were pre-treated with EEAP (200 and 400 mg/kg, respectively), for seven days and cisplatin was administered on day 8. Group E1 received cisplatin only on day 1, groups F1 and G1 received cisplatin on day 1; 72 hours after EEAP (200 and 400 mg/kg) were administered, respectively, for 7 days. Administration of cisplatin was intraperitoneal, while EEAP was oral. Nephroprotective effects were evaluated using markers of oxidative stress (protein carbonyl, H2O2), histopathology and immunohistochemistry [Kidney injury molecule-1, Nuclear factor (erythroid-derived 2)-like 2]. Data were analysed using descriptive statistics and ANOVA at α0.05. Reduced BP caused by isoproterenol was restored to near normal values in group F (systolic BP 102.33±2.31 to 131.50±2.1 mmHg, diastolic BP 82.67±1.80 to iii 101.70±1.3 mmHg). Treatment in group G restored prolonged QT interval (140.21±4.10 to 75.55±3.01 ms), significantly reduced Malondialdehyde (5.98±0.44 to 4.24±0.39 μmol/mgprotein) and H2O2 (13.73±1.30 to 11.44±0.49 μmol/mgprotein), but increased SOD (1.74±0.05 to 1.98±0.14 U/mgprotein), and GST (19.99±0.68 to 23.99±1.38 units/mg tissue). Groups E and F had reduced cellular infiltration, downregulated CTnI and CRP, but upregulated IL-10 expressions. Treatment in group D1 significantly decreased protein carbonyl (40.12±5.93 to 23.85±6.45 nmoles/mgprotein), H2O2 (29.93±0.87 to 26.65±0.74 μmol/mgprotein), increased activities of SOD (48.28±1.24 to 52.94±2.17 U/mgprotein), GPx (52.95±2.00 to 55.92±1.92 mmole/GSH complex formed/min/mg protein) and downregulated Kim-1 but upregulated Nrf2 expressions. Andrographis paniculata at 200 mg/kg exhibited cardiac and renal protective activities through its antioxidant and anti-inflammatory properties. Therefore, it is a potential candidate in treatment of cardiovascular and renal diseases. Keywords: Andrographis paniculata, Phyto-antioxidant, Myocardial infarction, Renal injury Word count: 497 2018-04-01T00:00:00Z http://hdl.handle.net/123456789/334 NEUROPROTECTIVE EFFECTS OF GREWIA carpinifolia AGAINST VANADIUM-INDUCED TOXICITY IN MICE ADEBIYI, OLAMIDE ELIZABETH Nigeria is currently the second highest gas flaring country in the world with resultant environmental vanadium discharge. Vanadium toxicity is implicated in neurodegenerative changes via free radical production. The Blood-Brain Barrier permeability for synthetic antioxidants currently used in protecting the central nervous system in vanadium toxicity remains a challenge. Grewia carpinifolia (GC) possesses antioxidant property. This study was designed to investigate the protective activities of ethanol extracts of GC in vanadium-induced toxicity in mice. Safe doses of GC leaf and stem extracts (FHI-109693) were assessed in 50 mice equally divided and administered 100, 200, 400 and 800 mg/Kg of each extract orally for 28 days using standard haematological, biochemical and histopathological methods. Distilled water served as control. Protective effects of each extract at 100 and 200 mg/Kg following vanadium toxicity in 120 mice (control, vanadium, extract-treated and standard-treated with α-tocopherol) were studied using behavioural tests (open field, hanging wire and Morris water maze), hepatic enzymes, haematological and histological parameters. In vitro antioxidant and lipid peroxidation activities were measured using ABTS, DPPH and TBARS assays. Pure bioactive compounds were isolated from leaf and stem extracts by TLC, open column chromatography, HPLC and characterised by NMR and MS. Brain Uptake Index (BUI) of each compound was determined. Neuroprotective and antioxidant activities of pure compounds following vanadium-induced toxicity were evaluated in a separate cohort of 72 mice equally divided; control, vanadium-treated, vanadium alongside compounds with high BUI and standard-treated groups by behavioural tests, antioxidant enzymes‟ activities (catalase, SOD, GPx, GSH), oxidative stress markers (MDA, NO and H2O2) measurements and immunohistochemical expression of Myelin Basic Protein (MBP) in the brain. Data were analysed using one-way ANOVA at α0.05. There were no significant differences in haematological parameters at tested doses, however, significant increase in ALP (40.85±6.78 to 81.40±6.24 IU/L), congestion of hepatic sinusoids were observed at 800 mg/Kg following 28-day administration. The extracts at 200 mg/Kg increased line crossings (18.60±4.67 to 59.00±5.93), reduced rearing (73.25±7.23 to 10.00±1.82) in open field test and increased latent time on hanging wire (27.67±5.12 to 70.34±8.05 secs). It also decreased AST (81.20±10.06 to 45.00±7.07 IU/L), ALT (75.40±9.07 to 45.00±5.82 IU/L) levels, increased PCV (32.40±4.10 to 40.50±3.54%) and prevented disorganisation of Purkinje cells of the cerebral cortex caused by vanadium. The IC50 of ABTS, DPPH and TBARS by extracts were 0.32, 0.41, 0.21 mg/mL (leaf) and 1.98, 0.80, 0.30 mg/mL (stem), respectively. Bioactive compounds isolated were iii β-spinasterol, dibutyl phthalate, β-sitosterol, benzoic acid butyl ester and stigmasterol with BUI of 70.6%, 3.5%, 76.5%, 1.1% and 87.0%, respectively. Concurrent administration of β-sitosterol and stigmasterol significantly attenuated spatial learning deficits caused by vanadium than α-tocopherol by reducing escape latency (20.66±2.13 to 37.19±4.63 secs), grooming, rearing and stretch-attend posture frequency. They also significantly increased activities of catalase (28.72±1.04 to 11.04±1.79 IU/mg protein), SOD (38.63±3.17 to 12.06±1.03 U/mg tissue), decreased oxidative stress markers and increased MBP expression. β-sitosterol and stigmasterol isolated from Grewia carpinifolia crossed the Blood-Brain Barrier, exhibited potent antioxidant and neuroprotective activities. They are therefore potential candidates in treatment of vanadium toxicity. Keywords: Vanadium toxicity, Grewia carpinifolia, β-sitosterol, Stigmasterol, Neuroprotective Word Count: 498 2017-06-01T00:00:00Z