Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment.
The efficacy of Withania somnifera (Ws) to limit myocardial injury after ischemia and reperfusion was explored and compared to that of Vit E, a reference standard known to reduce mortality and infarct size due to myocardial infarction. Wistar rats (150-200 g) were divided into six groups and received orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were monitored. Hearts were removed and processed for histopathological and biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated. Postischemic reperfusion produced significant cardiac necrosis, depression of left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as an increase in MDA level (p < 0.05) in the control group rats as compared to sham group. The changes in levels of protein and GPx was however, not significant. Ws and Vit E favorably modulated most of the hemodynamic, biochemical and histopathological parameters though no significant restoration in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the synthesis of endogenous antioxidants compared to sham. Results indicate that Ws significantly reduced myocardial injury and emphasize the beneficial action of Ws as a cardioprotective agent.
Gupta
Suresh Kumar
SK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. skgup@hotmail.com
Mohanty
Ipseeta
I
Talwar
Keval Krishan
KK
Dinda
Amit
A
Joshi
Sujata
S
Bansal
Pankaj
P
Saxena
Amit
A
Arya
Dharamvir Singh
DS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D013482:Superoxide Dismutase / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology; D032341:Withania
D010936:Plant Extracts; D014810:Vitamin E; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione; D007545:Isoproterenol