This study tested whether CsA would decrease skeletal muscle oxidative stress and mitochondrial dysfunctions after
aortic cross-clamping related IR.
Methods: Forty-five Wistar rats were investigated. The sham group (n=8) had aortic exposure but no ischemia, the IR group (n=10) had aortic cross-clamping for 3 hours followed by 2 hours of reperfusion, and the IR+CsA group (n=9) had two intraperitoneal injections of 10 mg of CsA at 90 and 150 minutes of ischemia before reperfusion. Mitochondrial coupling (acceptor control ratio) https://www.selleckchem.com/products/8-bromo-camp.html and mitochondrial respiratory chain complexes’ activities were measured. Reactive oxygen species (ROS) production, cyclophilin D expression, and muscle inflammation were determined using dihydroethidium staining, Western blot, and immunohistochemistry, respectively. An additional 18 sham rats were investigated to determine CsA blood levels and the effects of CsA on mitochondrial respiration and calcium retention capacity,
a marker of mPTP opening, both in myocardium and gastrocnemius with and without CsA.
Results: Compared with sham, IR decreased mitochondrial coupling (1.38 +/- 0.06 vs 1.98 +/- 0.20; P=.0092), increased ROS production (3992 +/- 706 arbitrary units [AU] vs 1812 +/- 322 AU; P=.033), was associated with macrophage infiltration, and decreased maximal oxidative capacity (V-max: 4.08 +/- 0.38 mu mol O-2/min/g vs 5.98 +/- 0.56 mu mol O-2/min/g; check details HKI-272 datasheet P=.015). Despite IR, CsA treatment totally restored mitochondrial coupling (1.93 +/- 0.12; P=.023 vs IR), normalized ROS (1569 +/- 348 AU; P=.0098 vs IR), and decreased inflammation. The V-max was slightly enhanced (5.02 +/- 0.39 mu mol O-2/min/g; P=.33 vs IR; P=.35 vs sham). Compared with myocardium, gastrocnemius muscle was characterized by a decreased cyclophilin D content (-50%) associated with an earlier opening of mPTP (calcium retention capacity increased from 10.85 +/- 1.35 mu M/mg dry weight [DW] to 12.11 +/- 2.77 mu M/mg DW; P=.65; and from 11.07 +/- 1.67 to 37.65 +/- 11.41 mu M/mg DW; P=.0098
in gastrocnemius and heart, respectively).
Conclusions: Cyclosporine A normalized ROS production, decreased inflammation, and restored mitochondrial coupling during aortic cross-clamping. Incomplete V-max protection might be due to low cyclophilin D expression in gastrocnemius, preventing CsA from blocking mPTP opening. (J Vasc Surg 2013;57:1100-8.)”
“Sex steroid hormones have been implicated in the visuo-spatial abilities in the general population, as well as in the pathophysiology of schizophrenia. Nevertheless, almost nothing is known about the association between levels of testosterone and/or estrogen with brain activations during visuo-spatial processing in schizophrenia. The fMRI data collected during performance of a mental rotation task in 42 schizophrenia patients (21 women) and 42 matched controls, were correlated with the levels of testosterone and estrogen.