Abstract:
Background: Hepatic ischemia reperfusion (IR) injury is an inevitable risk after liver transplantation, characterized by a plethora of events leading to hepatocellular injury. Indeed, hepatic IR injury triggers high-mobility group box protein B1 (HMGB1) release that activates toll like receptor-4 (TLR4) and initiates a downstream signaling cascade to activate mitogen activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to produce inflammatory cytokines and chemokines as well as a state of oxidative stress. On the other hand, the endogenous negative feedback regulator, phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) axis, that reduces pro-inflammatory and apoptotic insults was inhibited and the expression nuclear erythroid-related factor-2 (Nrf-2) pathway that enhances the expression of antioxidant enzymes was downregulated.
Objective: This study examined the potential hepatoprotective effect of telluric acid (TELL), one of tellurium based compound, against the devastating effect of hepatic IR injury. In past, tellurium based compound had limited functional use, however they acquired considerable interest nowadays due to antioxidant and anti-inflammatory activities. The current study targeted HMGB1/ TLR4 cascade, in addition to PI3K/ Akt axis, and Nrf-2 pathway as possible mechanisms contributed to TELL’s effect.
Methods: Male Wistar rats were allocated into 3 groups (n=10): sham-operated, control IR and TELL (50 μg/kg). TELL was administrated once daily for seven consecutive days prior to the IR induction. Hepatic IR injury was established by inhibiting the blood supply to the left lateral and median hepatic lobes, which constitutes 70% of the rat liver mass.
Results: Pretreatment with TELL mitigated hepatic IR injury as manifested by decreased plasma aminotransaminases and lactate dehydrogenase activities. Also, TELL opposed IR induced elevation in tissue expression/activity of HMGB1, TLR4, myeloid differentiation primary-response protein 88 (MyD88), p-NF-κB p65, p-MAPKp38 and tumor necrosis factor-alpha (TNF-α). Moreover, TELL reduced the elevated thiobarbituric acid reactive substances along with increased both Nrf-2 and endothelial nitric oxide synthase (eNOS) protein expression, beside replenishment of hepatic reduced glutathione. In addition, TELL induced obvious upregulation of p-PI3K and p-Akt protein expressions together with restoration of histopathological changes in IR injury.
Conclusions: TELL purveyed conceivable novel hepatoprotective mechanisms and attenuated events associated with acute hepatic injury via inhibition of TLR4 downstream axis and activation of Nrf-2 and PI3K/Akt signaling cascades. Thus, TELL may provide a novel therapeutic potential for complications of hepatic IR injury.

Biography:
Educational Background:
Bachelor degree in Pharmaceutical Sciences from Faculty of Pharmacy, Cairo University, May 2011
Master degree in Pharmaceutical Sciences (Pharmacology & Toxicology) from Faculty of Pharmacy, Cairo University, 2015
Doctor of Philosophy in Pharmaceutical Sciences (Pharmacology & Toxicology) from Faculty of Pharmacy, Cairo University, 2018
Career History and Professional Experience:
Lecturer of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University
Assistant Vice Dean for Graduates and Research Affairs, Faculty of Pharmacy, Cairo University
General Coordinator of Continuous Pharmacy Education Center, Faculty of Pharmacy, Cairo University
Member of Science and Technology Development Fund (STDF) research grant project entitled “To Determine the Capability of the Cardioprotective Cyclocreatine Phosphate to Reduce the Progression of Myocardial Infarction to Heart Failure in the Standard ISO Rat Model” (2018).
Member of the Erasmus project entitled “IT-based international diploma and professional certificate in clinical toxicology”-ITCT (2015).
Research interest and Publications:
Research interest: Molecular Neuropharmacology, Clinical Toxicology, Signal transduction pathways, Neuroscience, Inflammation, Pharmacovigilance and Gastrointestinal system.
Telluric acid ameliorates hepatic ischemia reperfusion-induced injury in rats: Involvement of TLR4, Nrf2, and PI3K/Akt signaling pathways “published at Biochemical Pharmacology 168 (2019):404-411, August 2019.
The Mas receptor as a future perspective in Parkinson’s disease “published at Journal of Neurology & Neuromedicine 3(4): 65-68, August 2018
Neurorestorative role of intrastriatal angiotensin 1-7 in 6-hydroxydopamine hemiparkinsonism by dual angiotensin 1-7/MASR axis activation and HMGB-1/RAGE signaling inhibition “published at World Congress of Pharmacology, Kyoto, Japan, July 2018
Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis “published at Biochemical Pharmacology 151 (2018) 126–134, February 2018.

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