ATPases play a significant role

ATPases play a significant role in the contraction and relaxation cycles of the 5-Azacytidine Supplier by maintaining normal ion levels within the myocyte. Several factors are known to alter the activities of ATPases especially lipid peroxidation and membrane fluidity. It has been reported that isoproterenol treatment resulted in a decrease in the activities of membrane bound ATPases [25]. The loss of ATPase activity in the ischemic stage may be responsible for causing not only functional damage but also reversible necrotic changes in the involved myocardial cells. Inactivation of membrane-bound ATPases has been correlated with peroxidation of membrane lipids [26]. Peroxidation of membrane lipids is believed to inactivate ATPases due to oxidation of thiol groups present in their active site and consequent conformational changes in the enzyme structure [27]. Decreased Ca2+-ATPase activity can increase intracellular free calcium and hence alter the signal transduction pathways and cellular fluidity [28]. The diminished activities of cardiac membrane-bound Na+,K+-ATPase and Ca2+-ATPase were generally countered by dietary interventions with fenugreek or fenugreek+garlic. Garlic has been shown to exhibit a cardio protective effect against ischemic injury by inhibiting lipid peroxidation and thus enhancing the recovery of cardiac function [29]. The antioxidant effect of fenugreek and garlic is probably responsible for the decrease in the activities of cardiac marker enzymes in serum with concomitant increase of the same in the heart tissue observed previously [9]. Antioxidant potential of fenugreek and garlic has been recently reviewed [4]. Lipid peroxidation in vivo has been identified as one of the basic deteriorative reaction during myocardial ischemia [30]. Lipid peroxides were higher in serum and heart as a result of isoproterenol administration. Peroxidation of endogenous lipids might be a major factor involved in the cytotoxic effect of isoproterenol. Pretreatment of rats with mangiferin and squalene have been shown to significantly decrease lipid peroxides both in serum and heart tissue in isoproterenol infarcted rats [31,32]. Ceruloplasmin is an extracellular antioxidant that can scavenge superoxide radicals [33] and inhibit ferritin dependent lipid peroxidation by catalyzing the oxidative re-incorporation of released iron into ferritin. Since ceruloplasmin has both ferro oxidase and copper-binding capacity, it could have been used more to neutralize the excess amount of free radicals and hence isoproterenol induced myocardial infarcted rats showed a decreased level of ceruloplasmin. The decreased levels of serum ceruloplasmin in normal as well as in HCD-fed situation during induction of myocardial infarction by isoproterenol administration was significantly countered by dietary fenugreek and garlic, the beneficial effect being higher in the case of fenugreek+garlic. Dietary fenugreek and garlic by their antioxidant effect would have prevented the loss of ceruloplasmin, thereby reducing the iron and copper mediated myocardial damage. Total iron binding capacity is inversely related to the risk of myocardial infarction [34,35]. The restoration of iron binding capacity by dietary interventions with fenugreek, garlic, fenugreek+garlic is consistent with proportionate decreases in free iron concentration in serum. Similar increases in iron binding capacity following mangiferin and garlic oil administration have been reported in experimentally infarcted rats [29,36]. In isoproterenol induced myocardial necrosis, free iron is released from heme containing proteins–hemoglobin and myoglobin with concomitant decrease in iron-binding capacity. Increased mobilization of iron from ferritin in the heart by the enzyme xanthine oxidase and over-production of free radicals results in myocardial damage [37]. The elevated levels of serum iron upon isoproterenol administration in these rats was significantly countered by dietary fenugreek, garlic, and fenugreek+garlic, the effect being higher in the case of combination. The increased plasma iron binding could have prevented hemolysis and iron catalyzed lipid peroxidation. This could be the reason for the decreased level of iron and increased plasma iron binding capacity in fenugreek/garlic pretreated rats.