RESULTS

The successive application of chi-square tests revealed that U-74389G enhanced the CPKl by 144.0769-fold [143.9114 - 144.2425] more than Epo at 1h (p-value=0.0000), by 3.987264-fold [3.979742 - 3.9948] more than Epo at 1.5h (p-value=0.0000), by 2.567192-fold [2.563487 - 2.570902] more than Epo at 2h (p-value=0.0000), less by 0.7974539-fold [0.7954859 - 0.7994269] (p-value=0.0000) without drugs and by 4.09626-fold [4.092989 - 4.099534] more than Epo whether all variables have been considered (p-value=0.0000).

DISCUSSION

The unique available study investigating the hyperkinasemic effect of U-74389G on CPKl was the preliminary one¹. Although the most famous activities of neuroprotection and membrane-stabilization properties, it accumulates in the cell membrane, protecting vascular endothelium from peroxidative damage but hardly penetrates the blood-brain barrier. It elicits a beneficial effect in ototoxicity and Duchenne muscular dystrophy. It increases γgt, superoxide dismutase (SOD) and glutathione (GSH) levels in oxygen-exposed cells. It treats septic states and acts as immunosuppressant in flap survival. It prevents the learning impairments, it delays the early synaptic transmission decay during hypoxia improving energetic state of neurons. It shows antiproliferative properties on brain cancer cells and is considered as a new promising anti inflammatory drug for the treatment of reperfusion syndrome in IR injuries.

The same authors confirmed2 the short-termhyperkinasemiceffect of Epo preparations in non iron deficient individuals. Quan W et al showed3 that Magnesium lithospermate B (MLB) significantly increased phosphorylation of Akt and that this phosphorylation can be partially inhibited by phosphoinositide 3-kinase/Akt inhibitor. The results also showed that MLB prevents I/R-induced myocardial damage by reducing necrosis and apoptosis in H9c2 cardiomyocytes, improving myocardial function in rat hearts. Yoshino T et al concluded4 a temporal induction of preconditioning actions of the aldosterone cascade, at a physiological dose, having favorable effects on cardiac functional recovery in left ventricular contractility and left ventricular end-diastolic pressure associated4 with a reduced activity of creatine phosphokinase released into the perfusate after injury following ischemia-reperfusion in a MR-independent manner male in Wistar rat Langendorff hearts. Takhtfooladi H et al alleviated5 the metabolic injuries in the skeletal muscle ischemia and reperfusion in this experimental model after tramadol treatment in a rat hind limb ischemia-reperfusion model. Dianat M et al concluded6 at a more significant decrease in the CPK levels in groups that had received combined treatment in comparison with vanillic acid (antioxidant) or losartan (selective angiotensin II (ANG-II) type 1 receptor (AT1R) blocker alone and hence, protects myocardium against I/R-induced oxidative stress injuries in isolated rat hearts. Liao Z et al strikingly found7 that resveratrol downregulates voltage-dependent anion channel 1 (VDAC1), leading to prevention of mitochondrial permeability transition pore opening and cardiomyocyte apoptosis; decreased the creatine phosphokinase activities; and reduced the infarction size. The data also revealed that long-term oral intake of resveratrol sets nutritional preconditioning to cope with myocardial I/R injury. Zhang N et al showed8 that preoperative trimetazidine therapy appears to have a positive effect on myocardial preservation along with significantly lower postoperative levels of CK, TnT and TnI, also in both the ≤12 and >12 h subgroup analyses in control coronary artery bypass grafting (CABG) patients. Lemarié J et al hypothesized9 that the triggering receptor expressed on myeloid cells (TREM)-1 acts as an amplifier of the immune response triggered by toll-like receptor engagement. TREM-1 inhibition by inhibitory peptide LR12 significantly improved these dysfunctions (P<0.03) and restricted infarct size, as assessed by lower creatine phosphokinase and troponin I concentrations (P><0.005) in a clinically relevant porcine model of acute myocardial infarction. Kashiwagi Y et al provided10 new insight into the significant role of sodium-glucose cotransporter 1 (SGLTs) in optimizing cardiac energy metabolism, at least during the acute phase of IRI, whether it is expressed in human hearts and significantly contributes to cardiac energy metabolism during ischemia-reperfusion injury (IRI) via enhanced glucose utilization. Phlorizin administration during IRI significantly impaired the recovery in left ventricular contractions and rate pressure product, associated with an increased infarct size, as demonstrated by triphenyltetrazolium chloride staining and creatine phosphokinase activity released into the perfusate in mice. Li CM et al demonstrated11 that the cardioprotective effect of ischemic post-conditioning was involved in the inhibition of PTEN, activation of the PI3K/Akt signal pathway and reduction of the cardiomyocyte apoptosis confirmed by serum creatine phosphokinase activity.Luo SY et al indicated12 that SB-710411 - a rat selective urotensin-II (U-II) receptor antagonist, which can block U-II-induced contraction of the aorta - inhibits U-IIinduced myocardial fibrosis and decreases myocardial UTR expression in myocardiac I/R injury of rats. Qiu LY et al revealed13 that treatment with SQS promoted protein kinase C ε (PKCε) which is able to mediate Cl‑ homeostasis - phosphorylation and inhibited sI/R-induced elevation of [Cl-]i, paralleled by the attenuation of mitochondrial membrane potential loss and ROS generation; eliciting cardioprotectionincreasing the viability and efficiently attenuating the creatine phosphokinase release in cultured cardiomyocytes. Takhtfooladi HA et al found significantly lower serum CPK levels14 (P><0.05) after low-level laser therapy (LLLT) which has a beneficial effect on the IR gastrocnemius muscle injury treatment in streptozotocin-induced diabetic male Wistar rats. Claroni C et al found15 the positive preconditioning impact of sevoflurane on IR injury expressed in the early postoperative hours, but not in the long-term ones since the creatine phosphokinase value was significantly lower in the BAL group only at the end of operation and not at other endpoints in patients undergoing free flap operation. Fujisaki N et al protected16 cardiac grafts from ischemia reperfusion-induced injury after pretreatment with CO gas before organ procurement effectively. Recipients of grafts from COexposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Donor pretreatment with CO altered the expression of 49 genes expressly represented on the array in a rat heterotopic cardiac transplant model. Kundra TS et al prevented17 skeletal muscle ischemia-reperfusion injury in patients undergoing aortobifemoral bypass operation after dexmedetomidine administration and CPK values assessments. Zeng G et al demonstrated18 that SIRT4, a mitochondrial-localized sirtuin is downregulated in cardiomyocytes both in vitro and in vivo models after MI-R. Functionally, SIRT4 overexpression decreases myocardial infarct size and serum creatine phosphokinase (CPK) level, and vice versa, SIRT4 depletion by siRNA increases myocardial infarct size and serum CPK level. Yin TC et al concluded19 that extracorporeal shock wave (ECSW) - adipose-derived mesenchymal stem cells (ADMSC) therapy is superior to either one applied individually since the microscopic findings of endothelial-cell biomarkers and number of arterioles expressedan opposite pattern of CPK, whereas the histopathology showed that muscle-damaged/fibrosis/ collagen-deposition areas exhibited an identical pattern of CPK among the five groups (all p>< 0.0001) for protecting against IR-induced thigh injury in rats.