ABSTRACT
The in vitro ability of Pothomorphe umbellata ethanolic crude extract to inhibit matrix metalloproteinase (MMP) in normal cornea and in cornea after alkali injury was demonstrated. Corneas of albino rabbits were injured with 1 N NaOH for 20 s. After 48 h the corneas were excised, homogenized and analyzed for MMP-9 (92 kDa), pro-MMP-2 (72 kDa) and MMP-2 (67 kDa) activity by gelatin zymography. The activity was also measured in untreated corneas. After electrophoresis of 20 æg protein, gels were incubated with 50, 100, or 250 µg/mL lyophilized hydroethanolic (1:1) root crude extract of P. umbellata standardized for 4-nerolidylcatechol (7.09 percent). The activity of the enzymes was compared with that of untreated gel. At 48 h after injury, the activity of all MMPs was increased compared with untreated eyes. When the gels were incubated with P. umbellata extract the activity of MMP-2, pro-MMP-2 and MMP-9 decreased in a dose-dependent manner. MMP-9 activity decreased by approximately 50 percent after incubation with 50 µg/mL and was completely abolished at 100 and 250 µg/mL of the extract. After incubation with 50 µg/mL the activity of pro-MMP-2 and MMP-2 also decreased by 50 percent. The activity of pro-MMP-2 was almost completely abolished after incubation with 250 µg/mL of the extract. For MMP-2 the incubation with 100 or 250 µg/mL of the extract of P. umbellata promoted a 10-fold decrease in activity. In conclusion, P. umbellata root crude extract can be useful as an alternative therapy to control MMP activity after corneal injury.
Subject(s)
Animals , Rabbits , Burns, Chemical/enzymology , Cornea/injuries , Enzyme Inhibitors/pharmacology , Eye Burns/chemically induced , Matrix Metalloproteinases/antagonists & inhibitors , Piperaceae/chemistry , Cornea/enzymology , Dose-Response Relationship, Drug , Enzyme Inhibitors/isolation & purification , Eye Burns/enzymology , Matrix Metalloproteinases/metabolism , Phytotherapy , Plant Extracts/pharmacologyABSTRACT
The circulatory effects of norepinephrine (4 * g/kg) and phenylephrine (20 */kg) were determined in anesthetized dogs withnormal plasma magnesium and with induced hypermagnesemia. Norepinephrine caused a 24% increased in heart rate by 103% increase in the systemic vascular, resistance index in normomagnesemic dogs, while with hypermagnesemia the variations were of 13% and 1%, respectively. Isoproterenol increased heart rate by 485 and 185 in dogs with normo- and hypermagnesemia, respectively.Phenylephrine increased the systemic vascular resistance index (74%) only in the normomagnesemic state.The effects of all the drugs were significantly defferent (P<0.01), without and with the simultaneous administration of magnesium sulfate (plasma magnesium, 1.3ñ0.2mEq/l and 6.8ñ1.1 mEq/l, respectively).We conclude that acute induced hypermagnesemia antagonizes the circulatory effects of adrenergic stimulation, a fact that may explain its antiarrhythmic and hemodynamic effects during acute myocardial ischemia
Subject(s)
Dogs , Animals , Hemodynamics/drug effects , Isoproterenol/antagonists & inhibitors , Magnesium/blood , Norepinephrine/antagonists & inhibitors , Phenylephrine/antagonists & inhibitors , Calcium/metabolism , Coronary Disease/physiopathologyABSTRACT
The efficacy of magnesium sulfate for prevention of ventricular fibrillation was compared with that of the calcium blocker verapamil and other antiarrhythmic drugs in 54 open-chested anesthetized dogs during a 3-h ligation of the circumflex coronary artery. Latency time to fibrillation, incidence of fibrillation and hemodynamic parameters were assessed. 2. Ventricular fibrillation ocurred in 11 of 14(79%) control dogs, in 2 of 8(25%) dogs treated with magnesium sulfate (100 mg/Kg) and in none of 8 animals treated with verapamil (0.2 mg/Kg) (P = 0.014 and P = 0.0004, respectively, in comparison with controls); lidocaine (60 mg followed by 4 mg/min), amiodarone (5mg/kg) and propafenone (4mg/Kg) had no effect on the incidence of fibrillation. 3. The latency time to fibrillation was 11.6 ñ 9.1 min in controls and it was shortened to 4.0 ñ 3.8 min (P = 0.039) in dogs treated with propafenone, but was unaffected by other drugs. 4. There was no correlation between pre-occlusion heart rate or blood pressure and fibrillation incidence. 5. In this experimental model, magnesium sulfate infusion had a protective effect against ventricular fibrillation that was similar to verapamil, suggesting that magnesium sulfate may be useful as an antifibrillatory agent during acute ischemia