Andrographolide protects against isoproterenol-induced myocardial infarction in rats through inhibition of L-type Ca2+ and increase of cardiac transient outward K+ currents.

Myocardial infarction (MI) is the irreversible injury of the myocardium caused by prolonged myocardial ischemia and is a major cause of heart failure and eventual death among ischemic patients. The present study assessed the protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats. Animals were randomly divided into four groups: Control (Ctr) group received 0.9% saline solution once daily for 21 days, Isoproterenol (Iso) group received 0.9% saline solution once daily for 19 days followed by 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21, Andrographolide (Andro) group received 20 mg/kg/day of andrographolide for 21 days, and Andrographolide plus Isoproterenol (Andro + Iso) group received 20 mg/kg/day of andrographolide for 21 days with co-administration of 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21. After all treatments, cardiac-specific parameters that define cardiac health and early subacute MI were measured in all groups using both biophysical and pharmacological assay methods. Isoproterenol administration significantly (P < 0.05) increased cardiac mass indexes, systemic cardiac biomarkers, infarct size and caused cardiac histological alterations; significantly (P < 0.05) increased heart rate, QRS & QTc intervals and caused ST-segment elevation; significantly (P < 0.05) increased myocytes shortening, action potential duration (APD), L-type Ca2+ current (ICa,L) density and significantly (P < 0.05) decreased transient outward K+ current (Ito) density typical of the early subacute MI. Interestingly, pretreatment with andrographolide prevented and or minimized these anomalies, notably, by reducing ICa,L density and increasing Ito density significantly. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to early subacute infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI.

Micrurus surinamensis Peruvian snake venom: Cytotoxic activity and purification of a C-type lectin protein (Ms-CTL) highly toxic to cardiomyoblast-derived H9c2 cells.

Micrurus surinamensis (Cuvier, 1817), popularly known as aquatic coral snake, has a broad geographic distribution in the Rainforest of South America. The purpose of this study was to investigate the cytotoxic effect caused by M. surinamensis venom in H9c2 cardiomyoblast cells and to identify protein components involved in cardiotoxic processes. Venom cardiotoxic potential is evidenced by cell viability reduction in a concentration-dependent manner. We have purified one of venom components responsible for this effect after three chromatographic steps: a cytotoxic 23.461 kDa protein, as determined by mass spectrometry. A 19-residue sequence (DCPSGWSSYEGSCYNFFQR) of the purified protein was deduced by MS/MS and exhibited high homology with N-terminal region of C-type lectin from snake venoms. This protein was named Ms-CTL. Morphologically, H9c2 incubation with Ms-CTL led to a significant cellular retraction and formation of cellular aggregates, as observed by microscopy phase-contrast images. Our results indicate that M. surinamensis venom is highly toxic to H9c2 cardiomyoblast cell and less or not cytotoxic to other cell lines, such as HaCat, VERO and U373. Results presented herein will help understanding the mechanisms that underlie cellular damage and tissue destruction, being useful in the development of alternative therapies against these coral snake bites.

Insights into anti-parasitism induced by a C-type lectin from Bothrops pauloensis venom on Toxoplasma gondii.

Here we evaluate the effects of BpLec, a C-type lectin isolated from Bothrops pauloensis snake venom, on Toxoplasma gondii parasitism. BpLec (0.195-12.5 µg/mL) did not interfere with HeLa (host cell) viability by MTT assay, whereas higher doses decreased viability and changed HeLa morphology. In addition, the host cell treatment before infection did not influence adhesion and proliferation indexes. BpLec did not alter T. gondii tachyzoite viability, as carried out by trypan blue exclusion, but decreased both adhesion and parasite replication, when tachyzoites were treated before infection. Galactose (0.4 M) inhibited the BpLec effect on adhesion assays, suggesting that BpLec probably recognize some glycoconjugate from T. gondii membrane. Additionally, we performed cytokine measurements from supernatants collected from HeLa cells infected with T. gondii tachyzoites previously treated with RPMI or BpLec. MIF and IL-6 productions by HeLa cells were increased by BpLec treatment. Also, TGF-ß1 secretion was diminished post-infection, although this effect was not dependent on BpLec treatment. Taken together, our results show that BpLec is capable of reducing T. gondii parasitism after tachyzoite treatment and may represent an interesting tool in the search for parasite antigens involved in these processes.