The effect of p38 map kinase inhibitor on molecular genetic and biochemical parameters in doxorubicin cardiotoxicity

Aim: The effects of p38 MAPK inhibitor application on molecular genetic and biochemical parameters in doxorubicin induced cardiotoxicity model in rats. Material and Method: 48 male Wistar albino rats were divided into 4 groups each containing 12 rats per group; The p38 MAPKi, DOX, C, DOX + p38 MAPKi group. In the heart tissue, expressions of Kav-3, MMP-2, UCP-2, Kavin-4 genes were performed by real-time PCR, while analysis of SOD, MDA, GSH, CAT levels were determined spectrophotometrically. Heart function tests were applied to rats. Histopathological examinations in the heart tissue were performed with hemotoxylin-eosin staining. Results: DOX group MMP-2 gene expression was increased compared to C and p38 MAPKi group. It was found that UCP-2 gene expression in DOX, p38 MAPKi, DOX + p38 MAPKi groups increased compared to the K group (p < 0.05). UCP-2 gene expression in DOX + p38 MAPKi group showed a decrease compared to the DOX group (p < 0.05). There was a statistically significant increase in tissue CAT activity in the DOX and DOX + p38 MAPKi group compared to the C and p38 MAPKi group (p < 0.05). Elevated MDA level in the DOX group was found to be significant compared to the C, p38 MAPKi and DOX + p38 MAPKi groups(p < 0.05). Increased SOD activity in DOX, p38 MAPKi and DOX + p38 MAPKi groups was found to be significant compared to the C group (p < 0.05). Histopathologically, congestion-hemorrhage anad degenerated cardiomyocyte density in the DOX group were found to be statistically higher than the C and p38 MAPKi groups (p < 0.05). Conclusion: We consider that the administration of p38 MAPK inhibitor after doxorubicin may provide a protective effect in the protection of heart damage on some mechanisms in the heart tissue. Key Words: MMP-2, Caveolin-3, Cavin-4, p38 MAPK, cardiotoxicity