Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Endoplasmic reticulum stress (ERS) has grabbed the research attention in the past years as a double edged signaling that can restore homeostasis while may eventually lead to apoptosis. Despite the research advances in this area, the role of receptor tyrosine kinase in such pathway as well as the involvement of this cue in sepsis pathophysiology is still enigmatic. Hence, the current study was aimed to elucidate the ERS-releasing ability of recombinant human growth hormone (rhGH/somatropin) against the in house-developed vascular endothelial growth factor receptor (VEGFR)-2 antagonist, named WAG-4S, in rats with septic encephalopathy. The daily treatment with rhGH/somatropin, at a dose of 300 og/kg for 7 days post-induction of mid-grade sepsis by cecal ligation and perforation (CLP) improved the horizontal/vertical activities in the open field task, the short/long term memories in the object recognition challenge, the time dwell and the number of target quadrant entries in the Morris water maze. The growth factor treatment limited the CLP-induced endotoxemia, proved by decreased endotoxin level, while WAG-4S provoked it. The growth factor also activated VEGFR2 and mammalian target of rapamycin (mTOR) expression

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