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

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 99mTechnetium 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 Cmax (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 Tmax (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 Cmax (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.

Nadp+ biosynthesis by rats receiving a pellagragenic diet

Rats showing signs of pellagra-like disease associated with gelatin ingestion were injected with [14C}-nicotinic acid into the portal vein and the incorporation of the label into hepatic NAD+ and NADP+ was determined. The quantity of NADP+ synthesized within 1 h after [14C]-nicotine acid injection by the experimental group, supplemented or not with dietary niacin, was 75% lower than that synthesized by the control group fed a casein control diet (141nmol h-1 g-1). The NAD+ and NADP+ contents of the liverof the experimental animals were 245 and 93 *g/g liver, respectively, i. e., significantly lower than those for the controls (597 and 210 *g/g liver, respectively). Dietary supplementation with niacin increased the NAD+ content to 317 */g liver but had no statistical effect on NADP+ content (75 *g/g liver) or NADP+ synthesis (46.5 in the free niacin group vs 37.0 nmol h-1 g-1 in the niacin-supplemented group). Therefore, NAD+ content did not seem to limit NADP+ synthesis. These results that the lower availably of NADP+ is responsible, at least in part, for some metabolic derangements in pellagra-like disease, such as a decrease in the activity of NADP+-dependent enzymes observed in quail muscle