Modulation of oxidative/nitrosative stress and inflammatory response by rapamycin in target and distant organs in rats exposed to hindlimb ischemia/reperfusion: The role of mTOR.

The objective of the current study was to evaluate the role of the mTOR in oxidative/nitrosative stress and inflammation in hindlimb I/R-induced injury in target and remote organ injuries. In rats subjected to I/R, an increased expression of ribosomal protein S6 (rpS6), inhibitor κB (IκB)-α, nuclear factor-κB (NF-κB) p65, iNOS, cyclooxygenase (COX-2), gp91phox, and levels of tumor necrosis factor (TNF-α), nitrite, nitrotyrosine, malondialdehyde (MDA) and the activities of myeloperoxidase (MPO) and catalase in the tissues and/or sera were detected. Treatment with rapamycin, a selective inhibitor of mTOR, reversed all the I/R-induced changes as manifested by its' anti-inflammatory and antioxidant effects in kidney and gastrocnemius muscle of rats. Collectively, these findings suggest that rapamycin protects against I/R-induced oxidative/nitrosative stress and inflammation leading to organ injuries via suppression of mTOR/IκB-α/NF-κB signaling pathway. PMID: 31505123 [PubMed - as supplied by publisher]
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research