Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-α) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-α, TNF-α type-1 receptors, and nuclear factor kappa B (NF-κB). Thus TNF-α inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade.
Myocardial ischemia induces 5‐lipoxygenase (LOX) translocation and leukotriene production in the heart. Leukotrienes increase inflammatory responses and could thereby aggravate ischemic injury. This study aimed to investigate whether 11‐Keto‐β‐boswellic (a selective 5‐LOX inhibitor) in three different dose levels exert protective effect on myocardial ischemia reperfusion injury in an in vivo rat heart model. In the current study, forty rats were randomly assigned into 5 groups. GP1: sham operated, Gp 2: ischemic reperfusion (I/R) model while Gps 3,4,5 received 11‐ Keto‐boswellic acid in doses 250, 500, 1000 mg/kg respectively via an oral gavage for 7 days, then subjected to I/R which was induced by ligation of left anterior descending coronary artery for 45 minutes followed by 4 hours reperfusion. At the end of the experiments hearts were excised for analysis. There were significant elevation in the expression of nuclear factor (erythroid‐derived 2)‐like 2, heneoxygenease‐1 and restoration of glutathione peroxidase in a dose dependent manner. Furthermore, there were significant and dose dependent reduction in elevated myeloperoxidase, reduction in the expression of nuclear factor kappa B, tumor necrosis factor ‐α, 5‐LOX, cyclooxygenase‐2 and intercellular adhesion molecule 1 in the heart tissues. We concluded that 11‐Keto‐boswellic acid exerts a protective effect in myocardial I/R injury through mechanisms related to enhancement of antioxidant capacity and prevention of inflammatory cascades.
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