CoQ10 augments candesartan protective effect against tourniquet-induced hind limb ischemia-reperfusion: Involvement of non-classical RAS and ROS pathways

Tourniquet is a well-established model of hind limb ischemia-reperfusion (HLI/R) in rats. Nevertheless, measures should be taken to alleviate the expected injury from ischemia/ reperfusion (I/R). In the present study, 30 adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6): control, HLI/R, HLI/R given candesartan (1 mg/kg, P.O); HLI/R given Coenzyme Q10 (CoQ10) (10 mg/kg, P.O); HLI/R given candesartan (0.5 mg/kg) and CoQ10 (5 mg/kg). The drugs were administered for 7 days starting one hour after reperfusion. Candesartan and CoQ10 as well as their combination suppressed gastrocnemius content of angiotensin II while they raised angiotensin-converting enzyme 2 (ACE2) activity, angiotensin (1-7) expression, and Mas receptor mRNA level. Consequently, candesartan and/or CoQ10 reversed the oxidative stress and inflammatory changes that occurred following HLI/R as demonstrated by the rise of SOD activity and the decline of MDA, TNF-a, and IL-6 skeletal muscle content. Additionally, candesartan and/or CoQ10 diminished gastrocnemius active caspase-3 level and phospho-p38 MAPK protein expression. Our study proved that CoQ10 enhanced the beneficial effect of candesartan in a model of tourniquet-induced HLI/R by affecting classical and non-classical renin-angiotensin system (RAS) pathway. To our knowledge, this is the first study showing the impact of CoQ10 on skeletal muscle RAS in rats. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study demonstrated that candesartan and CoQ10, either alone or in combination, reversed oxidative stress and inflammatory changes in a model of tourniquet-induced hind limb ischemia-reperfusion (HLI/R) in rats by affecting the renin-angiotensin system (RAS) pathway. It is the first study to show the impact of CoQ10 on skeletal muscle RAS in rats.