Comparison of the protective effects of vanillic and rosmarinic acid on cardiac tissue: Lower limb ischemia-reperfusion model in rats.

Background: Ischemia/reperfusion injury is one of the most challenging postoperative situations in vascular surgery, both in elective procedures with prolonged clamping time and in delayed emergency cases with vascular occlusion. The inflammatory response that develops during ischemia and the oxygen-free radicals that proliferate during reperfusion have detrimental effects on the brain, heart, and kidneys. In this study, we aimed to compare the effects of vanillic and rosmarinic acid in preventing ischemia/reperfusion injury in a lower limb ischemia-reperfusion model in rats.

Methods: Thirty-two female Sprague-Dawley rats weighing 185-240 g were randomly divided into four groups of eight animals each. Group 1 was designated as the control, Group 2 as ischemia/reperfusion (I/R), Group 3 as ischemia/reperfusion + vanillic acid (I/R + VA), and Group 4 as ischemia/reperfusion + rosmarinic acid (I/R + RA). In all groups except the control, the infrarenal abdominal aorta was clamped, and 60 minutes of ischemia followed by 120 minutes of reperfusion was performed. Vanillic acid was administered intra-abdominally 15 minutes before the start of reperfusion in Group 3, and rosmarinic acid in Group 4. At the end of the reperfusion phase, blood samples and hearts were collected, and the rats were euthanized. Histopathologically, myofibrillar edema, myocytolysis, focal hemorrhages, and infiltration of polymorphonuclear leukocytes (PMNL) in cardiac tissue were examined. Total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), 8-OH-deoxyguanosine, lactonase, and arylesterase activity were measured in blood samples.

Results: Myofibrillar edema was most pronounced in the I/R group and less pronounced in the I/R + VA and I/R + RA groups (p=0.005 and p=0.066, respectively). There was no difference between the ischemia/reperfusion groups regarding myocytolysis, focal hemorrhage, and PMNL infiltration (p>0.99). Among all groups, TOS and OSI were lowest in the control group, while TAC was highest. TAC was similar in the I/R + VA and I/R + RA groups but was significantly higher in these two groups than in the I/R group. The lactonase activity in the I/R + VA group was similar to that in the control group but was significantly higher compared to the I/R and I/R + RA groups.

Conclusion: Our study shows that vanillic and rosmarinic acids reduce myofibrillar edema in the heart after lower limb ischemia and increase TAC. However, vanillic acid increases the activity of lactonase, an enzyme known for its antioxidant effect, more than rosmarinic acid.