Therapeutic Effects of Rivastigmine in induced Cytokine Storm in Mice: Dose Standardization

Ahmed F. Abed Mansoor 1, Ahmed R Abu Raghif 2, Israa Mahdi Al-Sudani 3, Muhammed A. H. Aldabagh 4
1Department of Pharmacology College of Medicine Al Nahrain University/Iraq
2Department of Pharmacology College of Medicine Al Nahrain University/Iraq
3Ibn Sina University of Medical and Pharmaceutical Sciences, Baghdad, Iraq
4College of Medicine/Al Nahrain University, Baghdad, Iraq

ABSTRACT

Background: A cytokine storm release syndrome is a serious clinical systemic hyperinflammatory response that can be triggered by a variety of factors such as infections and certain drugs. It is a severe clinical condition that complicates infectious diseases, e.g., COVID-19, and non-infectious diseases, e.g., autoimmune diseases and cancer, and may lead to death. Objectives: Evaluation of the effect of Rivastigmine (RA) in Cytokine storm-induced in mice by lipopolysaccharide (LPS) and to explore their impact on Interleukine-1 β, Interleukine-6, Transforming growth factor-β and Tumor Necrosis Factor-α levels and Histopathological changes in Lungs. Methods: Animal: Swiss albino male mice were divided equally and randomly into 6groups (n=10): •Group AH: Healthy control group received no induction and no treatment. •Group LPS: induced by (LPS inducted 5 mg /kg), without treatment. •Group DMSO: Induced and treated with DMSO 1%. • Group CAR: treated with Rivastigmine 0.5 mg/kg. Results: Administration of LPS to Swiss albino mice caused a significant elevation of IL-1β, IL-6, TNF- α, and TGF-β levels and tissue histopathological changes when compared to the healthy control group. A highly significant histopathological improvement (P<0.001) in the tissue sections of the lung (hematoxylin & eosin) stain in comparison with those in the inducednon-treated group. Conclusion: Rivastigmine was found to be effective in attenuating and treating the induced cytokine storm by suppressing IL1β, IL-6, TNF-α, and TGF-β levels were comparable with Methylprednisolone><0.001) in the tissue sections of the lung (hematoxylin & eosin) stain in comparison with those in the induced non-treated group. Conclusion: Rivastigmine was found to be effective in attenuating and treating the induced cytokine storm by suppressing IL1β, IL-6, TNF-α, and TGF-β levels were comparable with Methylprednisolone

Keywords:AH: apparently healthy, LPS: Lipopolysaccharide, DMSO 1% Dimethyl sulfoxide 1%. RA: Rivastigmine, MP: methylprednisolone, RMPA: Rivastigmine, and methylprednisolone.