Pentoxifylline exerts anti-inflammatory effects on cerebral ischemia reperfusion-induced injury in a rat model via the p38 mitogen-activated protein kinase signaling pathway

Abstract

Pentoxifylline exhibits complex functions with extensive pharmacological effects and is used therapeutically due to its therapeutic effects and rapid metabolism in the body, with no cumulative effects and few side effects. The present study investigated the effects of pentoxifylline on cerebral ischemia reperfusion-induced injury (IRI) through suppression of inflammation in rats. Hematoxylin and eosin staining was performed to evaluate the number of neurocytes, and ELISAs were applied to measure tumor necrosis factor-α, interleukin-6, malondialdehyde and superoxide dismutase activities. Treatment with pentoxifylline significantly recovered the cerebral ischemia reperfusion-induced neurological deficit score and cerebral infarct volume in rats. In addition, pentoxifylline treatment significantly reversed the cerebral ischemia reperfusion-induced interleukin-6, tumor necrosis factor-a, malondialdehyde and superoxide dismutase levels in vivo. Furthermore, pentoxifylline significantly inhibited cyclooxygenase-2 and inducible nitric oxide synthase mRNA and protein expression in cerebral IRI mice. Treatment with pentoxifylline also significantly suppressed the expression of cleaved caspase-3 and p38 mitogen-activated protein kinase (MAPK) protein in cerebral IRI mice. These results indicate that the protective effects of pentoxifylline on cerebral IRI may occur via the p38 MAPK signaling pathway.