CARDIAC AND RENAL PROTECTIVE EFFECTS OF Andrographis paniculata LEAF EXTRACT IN MALE WISTAR RATS

Abstract

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