ABSTRACT
Loxosceles spp. (brown spiders) bites are responsible for the development of a syndrome consisting mainly of dermonecrotic lesions, and also systemic effects. Rabbits are one of the main experimental models used for better understanding the systemic and local effects of Loxosceles venom. The aim of this study is to evaluate the toxic and protective effects of rabbits immunized with Loxosceles spp. venom. Male New Zealand rabbits were allocated as a control group (CG; n = 5) that received adjuvant (Montanide) and phosphate-buffer saline (PBS), or as venom group (VG; n = 5) that received 21 µg of Loxosceles venom using Montanide as adjuvant. After five immunization cycles, a trial with 7 µg of Loxosceles intermedia (L. intermedia) venom was performed, and dermonecrotic lesions were measured. The rabbits were then euthanized, and their organs were collected for histopathology analysis. Rabbits that had undergone Loxosceles venom immunization protocol showed minor clinical disturbances during the experimental period. The used immunization protocol protected the rabbits against the toxic effect of the Loxosceles venom because they showed minor clinical disturbances during the experimental period.
ABSTRACT
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.
