Age effects on the pharmacokinetics of tityustoxin from Tityus serrulatus scorpion venom in rats

Abstract

The pharmacokinetics of scorpion venom and its toxins has been investigated in experimental models using adult animals, although, severe scorpion accidents are associated more frequently with children. We compared the effect of age on the pharmacokinetics of tityustoxin, one of the most active principles of Tityus serrulatus venom, in young male/female rats (21-22 days old, N = 5-8) and in adult male rats (150-160 days old, N = 5-8). Tityustoxin (6 µg) labeled with 99m Technetium was administered subcutaneously to young and adult rats. The plasma concentration vs time data were subjected to non-compartmental pharmacokinetic analysis to obtain estimates of various pharmacokinetic parameters such as total body clearance (CL/ F), distribution volume (Vd/F), area under the curve (AUC), and mean residence time. The data were analyzed with and without considering body weight. The data without correction for body weight showed a higher C max (62.30 ± 7.07 vs 12.71 ± 2.11 ng/ml, P < 0.05) and AUC (296.49 ± 21.09 vs 55.96 ± 5.41 ng h -1 ml -1 , P < 0.05) and lower T max (0.64 ± 0.19 vs 2.44 ± 0.49 h, P < 0.05) in young rats. Furthermore, Vd/F (0.15 vs 0.42 l/kg) and CL/F (0.02 ± 0.001 vs 0.11 ± 0.01 l h -1 kg -1 , P < 0.05) were lower in young rats. However, when the data were reanalyzed taking body weight into consideration, the C max (40.43 ± 3.25 vs 78.21 ± 11.23 ng kg -1 ml -1 , P < 0.05) and AUC (182.27 ± 11.74 vs 344.62 ± 32.11 ng h -1 ml -1 , P < 0.05) were lower in young rats. The clearance (0.03 ± 0.002 vs 0.02 ± 0.002 l h -1 kg -1 , P < 0.05) and Vd/F (0.210 vs 0.067 l/kg) were higher in young rats. The raw data (not adjusted for body weight) strongly suggest that age plays a pivotal role in the disposition of tityustoxin. Furthermore, our results also indicate that the differences in the severity of symptoms observed in children and adults after scorpion envenomation can be explained in part by differences in the pharmacokinetics of the toxin.

Hematological and biochemical profiles of rats submitted to experimental poisoning with Tityus serrulatus venom

“…The finding that scorpion venom was detrimental to renal function corroborates to previous studies in rats that have shown venom spreads rapidly from blood to tissues, especially kidneys, reaching a maximum concentration at around 15min after inoculation (Ismail and AbdElsalam, 1988;Santana et al, 1996;Nunan et al, 2003;2004). Furthermore, the occurrence of acute renal failure (ARF), with increased urea and uric acid concentration, diminished urinary volume, and tubular congestion, was reported in young patients that had been stung by T. serrulatus (Bertazzi et al, 2003).…”

Light and Transmission Electron Microscopical Changes Associated with Leiurus Quinqestriatus Venom in Rabbits

“…The lung edema is considered to be the main morphological change due to the venom of scorpion such as Tityus serrulatus, one of the most venomous scorpions. Its venom is made up of water-soluble and water-insoluble proteins, among which tityus toxin are the most toxic component (8). Transmission electron microscopy in the present study proved the appearance of eosinophils and suggested degranulation of its content had occurred and attributed to the respiratory distress observed clinically.…”

Cardiorespiratory evaluation of juvenile rats experimentally envenomed with Tityus serrulatus venom

“…serrulatus venom in rats has been investigated and the results indicate that toxin distribution and maximum concentration in the brain, heart and liver occur very rapidly in young animals compared to adult ones, whereas clearance and elimination are slower (39,40). The results of the present study corroborate previous findings regarding the susceptibility of young animals to scorpion venom.…”