dc.description.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
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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
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