Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation

Abstract

Background: Traumatic brain injury (TBI) is considered a major burden across the globe affecting both individuals and their families. Therefore, the present study was conducted to determine the protective effect of diphenhydramine (DPM) against TBI in experimental rats. Methods: The effect of DPM was evaluated on the cerebral edema (CE) and neuronal degeneration after the induction of experimental brain injury in rats. The effect of DPM was also investigated on the inflammatory cytokines, for example, tumor necrosis factor-α and interleukin 1β and oxidative stress markers, such as malondialdehyde, superoxide dismutase, and glutathione peroxidase. Western blot analysis was used to investigate the effect of DPM on B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cleaved caspase-3. Results: Results of the study suggest that DPM causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated group. Conclusion: DPM exerts a neuroprotective effect after TBI via the attenuation of oxidative stress, inflammation, and mitochondrial apoptosis pathways.

Docosahexaenoic Acid Protects Traumatic Brain Injury by Regulating NOX2 Generation via Nrf2 Signaling Pathway

“…In contrast, the time of secondary injury is relatively long, providing a treatment window. In the course of pathology, oxidative stress is considered as the core link of secondary injury [ 4 ]. Reactive oxygen species (ROS) are important substances involved in oxidative stress [ 5 ].…”

The role of diphenhydramine HCl on tumor necrosis factor-α levels in wistar rats with traumatic brain injury: An in vivo study

“…It is involved in the pathogenic processes of numerous central nervous system disorders, including cerebral ischemia, Parkinson's disease, and TBI. A study on TBI induced using a weight-drop model found that acute inhibition of post-traumatic TNF-α production or administration of TNF-binding protein decreased edema, cortical tissue damage, and hippocampal neurodegeneration during the acute post-traumatic period [ 4 ].…”

“…This drug also exhibits other pharmacological abilities, including sedative, anticancer, antiemetic, local anesthetic, and anticholinergic activities. DPM is also known to have significant antioxidant activity [ 4 , 5 ]. The purpose of this study was to investigate the role of DPM in inhibiting the post-TBI inflammatory reaction by assessing TNF-α levels as one of the important parameters involved in the inflammatory process.…”