Topical application of (S)-(-)-limonene is as effective as phonophoresis for improving oxidative parameters of injured skeletal muscle in rats.

The aim of this study is to investigate the effects of limonene, alone or associated with therapeutic ultrasound, on oxidative stress following skeletal muscle injury. Thirty male Wistar rats were divided into 5 groups: CTR-control, MI-muscle injury without treatment, TPU-therapeutic pulsed ultrasound alone, TPU + LIM-phonophoresis with 5% limonene, and LIM-5% limonene applied topically. Muscle injury was induced by a mechanical abrupt impact over gastrocnemius muscle. The animals were treated in the following intervals: 2, 12, 24, 48, 72, and 96 h after injury. Blood and gastrocnemius samples were collected 98 h after lesion for data analysis. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity, lipid peroxidation (TBARS) levels, catalase (CAT), and superoxide dismutase (SOD) activity were assessed. CK (p = 0.01), SOD activity (p < 0.01), and TBARS levels (p < 0.01) were increased after injury. There was no effect on LDH levels in any group. Phonophoresis (TABRS p < 0.01; SOD p = 0.01), TPU alone (TBARS p < 0.01; SOD p = 0.01), and LIM alone (TBARS p < 0.01; SOD p < 0.01) reduced TBARS levels and SOD activity after muscle injury. There was no change for CAT activity after injury. Only phonophoresis reduced CK activity after injury (p < 0.01). There was no difference between phonophoresis, TPU alone and LIM alone groups for TBARS, SOD, CAT, and LDH. Limonene alone and TPU alone were effective in reducing oxidative stress parameters after skeletal muscle injury. Only phonophoresis decreased CK activity. Skeletal muscle injury increases reactive oxidative species (ROS) levels and muscle proteins activity as creatine kinase (CK) and lactate dehydrogenase (LDH). Five percent limonene, alone or associated with therapeutic pulsed ultrasound, exhibited reduction of CK, superoxide dismutase (SOD) and catalase (CAT) activity, and lipid peroxidation markers (TBARS). Graphical abstract.

Dissection of the Effects of Quercetin on Mouse Myocardium.

Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 µM quercetin increased ICa,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V0.5 ) shifted towards more negative potentials from -13.06 ± 1.52 mV to -19.26 ± 1.72 mV and did not alter the slope factor. Furthermore, quercetin increased [Ca2+ ]i transient by 28% when compared to control. Quercetin accelerated [Ca2+ ]i transient decay time, which could be attributed to SERCA activation. In resting cardiomyocytes, quercetin did not change amplitude or frequency of Ca2+ sparks. In isolated heart, quercetin increased heart rate and decreased PRi, QTc and duration of the QRS complex. Thus, we showed that quercetin activates ß-adrenoceptors, leading to increased L-type Ca2+ current and cell-wide intracellular Ca2+ transient without visible changes in Ca2+ sparks.

Geraniol blocks calcium and potassium channels in the mammalian myocardium: useful effects to treat arrhythmias.

Geraniol is a monoterpene present in several essential oils, and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L-type Ca(2+) current, K(+) currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 µM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the IC a,L was reduced by 50.7% (n = 5) after perfusion with 300 µM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K(+) current (Ito ) (59.7%, n = 4), the non-inactivation K(+) current (Iss ) (39.2%, n = 4) and the inward rectifier K(+) current (IK 1 ) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain-induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L-type Ca(2+) and voltage-gated K(+) currents, ultimately acting against ouabain-induced arrhythmias.