Protective effects of curcumin against lithium-pilocarpine induced status epilepticus, cognitive dysfunction and oxidative stress in young rats

Abstract

Status epilepticus (SE), one of the most severe forms of epilepsy is regarded a medical emergency with considerable morbidity and mortality. Due to the limited efficacy and enormous side effects of currently available drugs, a search for new safe and effective therapeutic agents is critical using experimentally induced SE in animals. The lithium-pilocarpine (Li-Pc) model of SE is most suitable and frequently used for pathophysiological and management strategies of SE. Recent studies have shown significant potential of pharmacological, prophylactic or therapeutic use of curcumin (Cur) in many beneficial activities in the body including neuroprotection in neurodegenerative diseases and antioxidant properties. The present study describes anticonvulsive effects of Cur in Li-Pc induced SE in young rats. The effect of Cur was examined on the intensity and frequency of SE, cognitive behavior in water maze as well as on oxidative stress related enzymes in the brain. Besides its anticonvulsant effect, Cur significantly ameliorates SE-induced cognitive dysfunction and oxidative damages in the hippocampus and striatum areas of the brain. Possible therapeutic application of Cur as an anticonvulsant and as an antioxidant for the treatment of SE has a great potential and warrants further studies.

Keywords: Cognitive behavior; Curcumin; Oxidative stress; Pilocarpine; Status epilepticus; Water maze.

Figure 1

Performance in water-maze of animals that experienced SE along with their controls as well as the SE groups that were pretreated with curcumin (Cur). Mean latency to reach the hidden platform (y-axis) on each testing day (x-axis) shows that animals subjected to SE were slower in finding the platform (cognitive effect) than the controls on all four testing days. Treatment with Cur in varying doses was effective in improving the cognitive function. Abbreviations: Li = lithium chloride; Pc = pilocarpine; SE = status epilepticus; # represents significance as compared to control (p < 0.001), whereas ^∗∗ and ^∗∗∗ show p < 0.05 and p < 0.001, respectively, as compared to SE group by ANOVA.

Figure 2

Performance in water-maze of animals that experienced SE along with their controls as well as the SE groups that were pretreated with curcumin (Cur). The probe test shows that the SE-induced animals spent less time in the target quadrant than the control group. Pre-treatment of SE-induced animals with Cur had an attenuating effect and the animals spent more time in the target quadrant. Abbreviations and statistical significance are the same as in Figure 1.

Figure 3

Effect of curcumin (Cur) on lipid peroxidation content (TBARS) in hippocampus (A) and striatum (B) of young rats after Li–Pc induced SE. Abbreviations and statistical significance are the same as in Figure 1.

Figure 4

Effect of curcumin (Cur) on total glutathione level (GSH) in hippocampus (A) and striatum (B) of young rats after Li–Pc induced SE. Abbreviations and statistical significance are the same as in Figure 1.