e. cardiac arrhythmias, convulsions, pulmonary edema and death). Meanwhile intravenous administration (i.v.) of this low dose failed in producing these aforementioned effects, thus excluding a peripheral action of
the toxin ( Mesquita et al., 2003). In addition, a subcutaneous injection of TsTX in developing rats induced high amplitude discharges in nucleus tractus solitarius (NTS) ( Guidine et al., 2009), a medullary area well known for integrating cardiovascular reflexes ( Guyenet, 2006). These discharges were correlated to electrocardiographic changes, as atrioventricular blocks of different degrees, ectopic beats, sinus tachycardia or bradycardia and premature atrial and ventricular depolarization ( Guidine et al., 2009). Altogether, these evidences strongly suggest that CNS is involved in the cardiovascular changes observed CAL-101 datasheet in severe scorpion envenomation. It is known that the previous health condition of the patient may determine the severity of the envenomation (Ismail, 1995). In this context, malnutrition, buy Ponatinib another concerning syndrome that affects children in developing countries, represents an important factor to be considered (Ministério da Saúde, 2005). Deficiencies in dietary intake impairs the CNS (Agrawal et al., 2009, Egwim et al., 1986 and Lukoyanov
and Andrade, 2000), thus modifying the cardiovascular homeostasis (Benabe and Martinez-Maldonado, 1993, Bezerra et al., 2011a, Bezerra et al., 2011b, Loss et al., 2007, Martins et al., 2011, Oliveira et al., 2004 and Penitente et al., 2007) and the reactivity to centrally-active drugs (Almeida et al., 1996). Considering the high prevalence of both conditions (scorpion envenoming and malnutrition) in tropical countries, the hypothesis then raised is that malnutrition would change the cardiovascular responses produced by TsTX central injections. To test this hypothesis, we evaluated the increases in mean arterial pressure
and heart rate evoked by the i.c.v. injection of TsTX in rats fed L-NAME HCl a low protein diet. Tityustoxin (TsTX) was isolated from the venom of T. serrulatus scorpion as described by Gomez and Diniz (1966) ( Gomez and Diniz, 1966) and modified by Sampaio et al. (1983) ( Sampaio et al., 1983). The lyophilized toxin was solubilized in 500 μL of phosphate buffered saline (PBS). A known concentration of TsTX, as determined by Hartree ( Hartree, 1972), had serum bovine albumin as standard, and was used to determine the absorbance coefficient read at 280 nm: [protein] (Ag/ml)/A280 = 279. Further determination of TsTX concentration was done by the direct reading of samples in the spectrophotometer (Hitachi spectrophotometer, model 2001, Japan). After determining the concentration of protein (4.76 μg/μL), the initial pool was stored in volumes of 10 μL each, and stored at −20 °C until the time of the experiments. All experiments used the same initial pool of TsTX.