euro-toxicology-2016_scientifictracks-abstracts

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Volume 6, Issue 6(Suppl) J Clin Toxicol 2016
ISSN: 2161-0495, JCT an open access journal
Page 54
Notes:
Euro Toxicology 2016
October 24-26, 2016
conferenceseries.com
Toxicology & Applied Pharmacology
October 24-26, 2016 Rome, Italy
7th Euro-Global Summit on
Endothelin modulation of the cyclosporine/NSAIDs cardiovascular and renal interactions
Mahmoud M El Mas
Alexandria University, Egypt
The combined use of cyclosporine (CSA) and nonsteroidal anti-inflammatory drugs (NSAIDs) in arthritic conditions
is common in clinical practice. Because CSA or NSAIDs negatively impacts cardiovascular/renal functions when used
individually, we asked if these two drugmodalities would provokemore detrimental consequences when used together.The roles
of endothelin receptor, inflammatory and fibrotic pathways in these interactions have also been investigated. The treatment of
rats with celecoxib, but not indomethacin, blunted the CSA-evoked increases in blood pressure (BP), renal perivascular fibrosis
and arteriolar endothelin receptor expression (increases in ETA and decreases in ETB receptors). Alternatively, exaggerated
nephrotoxicity was seen upon simultaneous treatment with CSA plus indomethacin as evidenced by greater elevations in
serum creatinine and renal oxidative stress; renal infiltration of inflammatory cells and worsening of fibrotic and necrotic
profiles; and increased renal ET-1 and COX-2 expression. Unlike indomethacin, renal structural, oxidative, and molecular
abnormalities caused by CSA were largely eliminated in rats treated concurrently with celecoxib. ETA receptor blockade by
atrasentan ameliorated the hypertension and concomitant renal abnormalities caused by CSA/indomethacin regimen. On the
other hand, ETB receptor blockade (BQ788) caused celecoxib-sensitive hypertension and renal dysfunction and potentiated
the hypertensive effect of CSA. These findings suggest that COX-1/COX-2 selectivity of NSAIDs is pivotal for identifying
their cardiovascular and renal impacts on CSA toxicity. Celecoxib, but not indomethacin, is more advantageous as an add-on
therapy to CSA for arthritis management. The reliability of the current experimental findings needs to be corroborated with
appropriate clinical investigations.
Biography
Mahmoud M El Mas completed his PhD in 1990 from Joint Scheme between Leeds University, UK and Alexandria University, Egypt. He pursued Post-doctoral
Training at East Carolina University, USA. He is Chair of Pharmacology and Toxicology, Pharmacy, Alexandria University, Egypt and Chair of National Scientific
Committee on Pharmacology Faculty Promotion. His publications include: 107 papers in top international journals and 90 abstracts in international conferences.
His research expertise is: Cardiovascular/renal neurobiology of drugs of abuse (ethanol, nicotine) and immune-suppressants. He holds Editorial Board positions
in 9 international journals. His Awards are: Khalifa Award for Education in the Field of Scientific Research (United Arab Emirates), State Prize for Scientific
Encouragement (twice), State Prize for Scientific Excellence, ACDIMA award (Jordon), Alexandria University Honorary Award.
Mahmoud M El Mas, J Clin Toxicol 2016, 6:6(Suppl)