Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats

Nunan, E. A.; Moraes, Márcio Flávio Dutra; Cardoso, Valbert Nascimento; Moraes-Santos, Tasso

doi:10.1016/s0024-3205(03)00264-9

Cited by 59 publications

(45 citation statements)

References 24 publications

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“…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.…”

Section: Resultssupporting

confidence: 89%

Cardiorespiratory evaluation of juvenile rats experimentally envenomed with Tityus serrulatus venom

Pinto

Melo

Cruz

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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Accidental envenomation caused by Tityus serrulatus scorpions is very common in Brazil and may result in serious cardiorespiratory alterations that are frequently fatal to children. In the present study, the effects of T. serrulatus venom on the cardiorespiratory system of recently weaned male Wistar rats were evaluated. Fifteen animals were distributed into three groups (n = 5). The control group A received 400 μL ultrapure water by subcutaneous injection, while the experimental groups B and C were injected with scorpion venom (100 and 450 μg, respectively, in 400 μL water). Electrocardiogram (ECG) traces were obtained prior to the experiment, at five-minute intervals up to 30 minutes after treatment. At 40 minutes after envenomation, the animals had severe acute symptoms and were subsequently anesthetized for blood collection by means of intracardiac puncture. Biochemical profiles for the cardiac muscle were established by colorimetric analysis of creatine kinase (CK) and CK-MB isoenzyme. Semiquantitative analysis of troponin was performed using the immunochromatographic assay. Following euthanasia, the lungs and hearts were removed and subjected to histopathological examination. All experimental animals had ECG alterations compatible with electrolytic imbalance, myocarditis and alterations of the cardiac conduction system. Envenomed animals had accentuated bradycardia at 25 and 30 minutes after venom inoculation. All experimental animals had myocardial lesions, which were confirmed by increased serum levels of CK and CK-MB, although there were no alterations in the serum concentration of troponin. Pulmonary hemorrhage was detected in whole lungs and microscopically confirmed by the presence of congested capillaries and erythrocytes in the alveolar parenchyma. In conclusion, T. serrulatus venom caused great cardiorespiratory damage to weaned rats.

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Section: Resultssupporting

confidence: 89%

Cardiorespiratory evaluation of juvenile rats experimentally envenomed with Tityus serrulatus venom

Pinto

Melo

Cruz

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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“…However, most of these studies have been performed on adult rats or mice. To the best of our knowledge, very few studies have investigated the disposition of TsTX in 21-22-day-old young rats (29).…”

Section: Discussionmentioning

confidence: 99%

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

Nunan

Arya

Hochhaus

et al. 2004

Braz J Med Biol Res

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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.

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“…Indeed, cerebral alterations were assumed to be the consequence of neurotransmitter releases [43][44][45][46][47][48][49][50][51]. More recently, similar structural damage in brain tissue (i.e., edema, hemorrhage, neuronal darkness) were evoked by a small scorpion toxin called Kaliotoxin isolated from Aah [52].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of the Androctonus Australis Hector Nanobody Nbf12-10 Antivenom to Neutralize Significantly the Toxic Effect and Tissue Damage Provoked by Fraction of Androctonus mauretanicus (Morocco) Scorpion Venom

R¹

2015

Biochem Pharmacol (Los Angel)

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Scorpion stings are life threatening in large parts of the world. Toxins from scorpion venom are responsible for severe metabolic and tissue disruption and immunotherapy is the only specific treatment able to neutralize the toxic effects of scorpion venom. The Androctonus mauretanicus (Am) is the most dangerous scorpion in Morocco, whereas in Tunisia Androctonus australis hector (Aah) is causing most casualties. In this work, we investigated the potential of NbF12-10, a new immunotherapeutic concept based on anti-toxin Nanobodies (Nbs) to neutralize Am scorpion venom. We first explored the immune cross-reactivity between Am and Aah scorpions venoms using anti-AahI and anti-AahII polyclonal, NbAahI'F12 (anti-AahI'), monospecific NbAahII10 (anti-AahII) monospecific and bispecific NbF12-10 (anti-AahI'/antiAahII) monoclonal antibodies and subsequently we study the histological damages observed after envenomation with the F3 toxic fraction of Am scorpion venom by intra-cerebroventricular (i.c.v) injection and the capacity of NbF12-10 to reduce tissue damage induced by F3 fraction after i.c.v administration of F3:NbF12-10 mixture, in mice. Results showed significant para-specific activity of anti-Aah polyclonal and monoclonal antibodies towards Am venom fractions. Histological investigations revealed severe tissue damage in brain, lung and liver after i.c.v. administration of F3 fraction. The NbF12-10 pre-mixed with F3 fraction showed an efficient neutralizing capacity against lethal effect of this toxic fraction. Moreover, in vitro pre-incubation of F3 with NbF12-10 at 8-fold molar excess led to significantly reduced tissue damage. Further, NbF12-10 displays a noteworthy potential to neutralize Am toxins and to rescue 50% of envenomed mice from dying. This study provides first evidence that NbF12-10 nano-therapeutic has promising prospective to treat scorpion envenoming in the Maghreb area.

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Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats

Cited by 59 publications

References 24 publications

Cardiorespiratory evaluation of juvenile rats experimentally envenomed with Tityus serrulatus venom

Cardiorespiratory evaluation of juvenile rats experimentally envenomed with Tityus serrulatus venom

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

Effectiveness of the Androctonus Australis Hector Nanobody Nbf12-10 Antivenom to Neutralize Significantly the Toxic Effect and Tissue Damage Provoked by Fraction of Androctonus mauretanicus (Morocco) Scorpion Venom

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