Effect Of Combination Treatment Of Candesartan And Curcumin On Traumatic Brain Injury In Mice

Abstract

The present study aimed to investigate the effect of combination treatment of candesartan and curcumin on traumatic brain injury in mice. Mice were treated orally with curcumin (100 mg/kg), candesartan (1 mg/kg) or a combination of them once daily for 7 days after induction of trauma. For the production of brain injury, we used the weight drop technique. Candesartan, an Ang II receptor blocker (ARB), was proven to possess many neuroprotective effects. On the other hand, curcumin is a major component extracted from the rhizome Curcuma longa, and has been extensively studied for its wide range of biological activities, including anti-inflammatory, anti-oxidant, anti-infection and antitumor properties. For which both of them are used in this study for attacking the devastating sequelae of TBI.

The behavioral effect of curcumin, candesartan and their combination on locomotor activity, learning and memory was successfully evaluated. Oxidative stress markers in brain tissues were also measured including lipid peroxide (MDA), superoxide dismutase (SOD) activity and total antioxidant capacity(TAC).ELISA kits were used to measure the inflammatory markers such as interleukin-1beta (IL-1β), Tumor necrosis factor alpha(TNF-α),prostaglandin E-2(PGE-2) contents.The apoptotic parameter,caspase-3 was also assessed in the brain homogenates.Finally, gene expression levels ofB-cell lymphoma 2 (BCL-2),nuclear factor-kappa B (NF-κB)and inducible nitric oxide synthase(iNOS)were also measured usingReverse transcription-polymerase chain reaction (RT-PCR) experiment.The brain tissue sections were collected on glass slides, deparafinized, stained by hematoxylin& eosin stainfor histopathologicalexamination using light electric microscope.

Traumatic brain injury group exhibited a significant decrease in short and long term memory as compared to sham group. Also, a decrease in locomotor activity was observed in TBI group.Further, TBI produced a surge in theMDA contentin brain tissues when compared to sham group. In addition, it caused a significant decrease in the activities of TAC and SOD.Theassessment of inflammatory markers revealed that TBI significantly elevated PGE-2,TNF-alpha and IL-1βlevels in brain tissue in comparison to sham group.The results illustrate the content of caspase-3 as a marker for apoptosis, where brain tissue exposed to TBI showed a great elevation in caspase-3.In addition, TBI had an inhibitory action on the B-cell lymphoma 2 (Bcl-2) gene expression.AlsoNF-κBand iNOS gene expression in brain tissue exposed to TBI was significantly increasedas compared to sham group.Histopathological evaluation of brain sections from the TBI group showedfocal gliosis in the cerebral cortex, associated with severe nuclear pyknosis and degeneration of the neurons. Degenerated neuronal cells were also found in hippocampus associated with nuclear pyknosis. Additionally, focal eosinophilic plagues formation was noticed in the striatum of cerebrum.