rabbits with myocardial injury induced by isoproterenol
J-point displacement (increased or lowered) on the ECG; frequency of ischemic arrhythmia
After pretreatment with XMLI, the J-point displacement on the ECG caused by isoproterenol can be significantly reduced, so that the J-point position is close to the normal equipotential line. And the frequency of ischemic arrhythmia can be significantly reduced.
rats with myocardial injury induced by isoproterenol
J-point displacement (increased or decreased) on the ECG; CPK, LDH in serum; MDA, SOD, GSH-PX in myocardial tissue
After pretreatment with XMLI, the J-point displacement on the ECG caused by isoproterenol can be significantly reduced, MDA level be reduced, CPK and LDH activity be reduced, GSH-PX and SOD activity be increased.
XMLI can increase intracellular Ca2+ level by activating T-type Ca2+ channels and inhibiting Na+/K+-ATPase. XMLI can also reduce the production of ROS and enhance the expressions of SOD-1, SOD-2, HO-1.
After 6 hours of asphyxia in neonatal rats, serum CK-MB level, myocardial NF-κB, and TNF-α expressions peaked. XMLI can significantly reduce serum CK-MB level, myocardial NF-κB, and TNF-α expressions.
cardiomyocyte activity; SOD; MDA; Caspase-3 activity; autophagy-associated protein LC3B activity
XMLI can reduce doxorubicin-induced cardiotoxicity, increase cell activity and SOD activity, and decrease MDA level, Caspase-3 activity, and protein LC3B accumulation.
healthy rats for preparing epirubicin-induced HF model
cardiac function; survival rate; body weight; LVPW thickness; EF; ECG; accumulation of collagen; expression of MMPs and TIMP4; expression of TGF-β1 mRNAs; expression of Ace, Ace2, Mas, and Agtr1 mRNAs; autophagy; expression of PI3K and AKT; the phosphorylation of P38 MAPK and ERK1/2
XMLI can enhance the survival rate of rats from epirubicin-induced HF. XMLI can prevent LV dilatation, improve cardiac function. And the treatment of the epirubicin rats with XMLI significantly recovered these changes, such as QT, QTc intervals and QRS duration. Furthermore, XMLI can significantly inhibit the accumulation of collagen, reduce the MMP9 and TGF-β1. XMLI can also decrease Beclin1 and Atg7, activate the PI3K/AKT signaling pathway and inhibit the ERK1/2 and P38 MAPK signaling pathways.
IL-1b; IL-6; TNF-α; expression of LC3, PINK1, Parkin, Nix, Beclin-1; Mitofusin1, Mitofusin2, Opa1, Drp1 and P62
XMLI can increase cell viability and the release of LC3 in H9C2 cells. XMLI can reduce the level of cTnI, CK-MB, IL-1b, IL-6, and TNF-α. XMLI can increase the protein and mRNA expression of PINK1, Parkin, Nix, Beclin-1 and decrease expression of Mitofusin1, Mitofusin2, Opa1, Drp1, and P62.
0.19, 0.38 and 0.76g/L XMLI can increase the content of Ca2+ in cardiomyocytes. This effect of 0.38g/L XMLI can be slightly inhibited by 40μmol/L verapamil (inhibition rate is 20%), however, this effect of 0.19 and 0.76g/L XMLI cannot be inhibited by 40μmol/L verapamil.
XMLI can increase [Ca2+]i in hypoxia and hypoxia-reoxygenated myocardium, increase SOD level and decrease MDA level. And this effect cannot be inhibited by verapamil.
HF mice with TAC surgery; H9C2 cells (rat cardiomyocytes)
LVPW thickness; EF; FS; phosphorylation of ERK1/2, AKT, and GSK3β; expression of GATA4 in the nucleus
XMLI can reduce the diastolic thickness of the LVPW, increase EF and FS. XMLI can inhibit the phosphorylation of ERK1/2, AKT, and GSK3β, subsequently inhibiting protein expression of GATA4 in the nucleus.
survival time; the lethal dose of BaCI2 in rabbits; the rate of sinus rhythm conversion
XMLI can significantly increase the lethal dose of BaCI2 in rabbits and prolong the survival time of rabbits. It prevents and reduces VPB, VT, and VF caused by BaCI2. It can also significantly improve the rate of sinus rhythm conversion.
