Assessment of the protective effect of KN-93 drug in systemic epilepsy disorders induced by pilocarpine in male rat

J Cell Biochem. 2019 Sep;120(9):15906-15914. doi: 10.1002/jcb.28864. Epub 2019 May 9.


Background and aims: Epileptic seizures occur as a consequence of a sudden imbalance between the stimuli and inhibitors within the network of cortical neurons in favor of the stimulus. One of the drugs that induce epilepsy is pilocarpine. Systemic injection of pilocarpine affects on muscarinic receptors. Increasing evidence has addressed the implication of KN-93 by blocking Ca2+ /calmodulin-dependent protein kinase II (CaMKII), suppressing oxidative stress and inflammation, and also reducing neuron decay. So, we aimed to evaluate the potential preventive effects of KN-93 in systemic epilepsy disorders induced by pilocarpine.

Materials and methods: In this animal study, male rats were divided into five groups including treatment group (KN-93 with the dose of 5 mM/10 µL dimethyl sulfoxide (DMSO) before inducing epilepsy by 380 mg/kg pilocarpine) KN-93 group (received 5 mM KN-93), control group, epilepsy group (received 380 mg/kg pilocarpine Intraperitoneal), and sham group (received 10 µL DMSO). Oxidative stress was assessed by measuring its indicators including the concentration of malondialdehyde (MDA), nitrite, glutathione (GSH), as well as the antioxidant activity of catalase. In addition, serum levels of proinflammatory mediators including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined.

Results: Pretreatment with KN-93 significantly reduced oxidative stress index by reducing the concentration of MDA, nitrite, and increasing the level of GSH. In addition, low concentrations of TNF-α and IL-1β were observed in hippocampus supernatant of KN-93 pretreated rats in comparison with the pilocarpine groups. Moreover, administration of KN-93 improved neuronal density and attenuated the seizure activity and behavior.

Conclusions: Overall, our findings suggest that KN-93 can effectively suppress oxidative stress and inflammation. Furthermore, KN-93 is able to attenuate seizure behaviors by preventing its effects on neuron loss, so, it is valuable for the treatment of epileptic seizures.

Keywords: KN-93; epileptic seizures; inflammation; oxidative stress; pilocarpine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / therapeutic use
  • Benzylamines / administration & dosage*
  • Benzylamines / therapeutic use
  • Injections, Intraperitoneal
  • Interleukin-1beta / blood
  • Male
  • Pilocarpine / adverse effects*
  • Protein Kinase Inhibitors / administration & dosage*
  • Rats
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / metabolism
  • Sulfonamides / administration & dosage*
  • Sulfonamides / therapeutic use
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / blood


  • Antioxidants
  • Benzylamines
  • IL1B protein, rat
  • Interleukin-1beta
  • Protein Kinase Inhibitors
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • Pilocarpine
  • KN 93