Effect of acute administration of 2,5-hexanedione on nociception in rats

Hexacarbon compounds are neurotxic to man and animals. These substance also inhibit various enzymes in vitro, including acetylcholinesterase. Since some cholinesterase inhibitor alter nociceptor we determined the effect of acute ip administration of 2,5-hexanedione on nociception in female Wistar rats (75-90 days old, 170-200g; 15-17 rats in each group) using a tail-flick apparatus. The rats were injected ip with vehicle solution (120mMNaCl containing 10 mM potassium phosphate buffer, pH 7.2) and 200, 400 or 800 mg/Kg of 2,5-hexanedione in a volume of 1 ml/Kg body weight. Tail-flick latencies were obtained 10, 30, 60 and 90 min after drug administration. All doses of 2,5-hexanedione caused antinociception (p<0.001) but the appearance and duration of the analgesia varied according to the dose of the drug. The highest dose tested (800 mg/Kg) caused analgesia from 10 to 60 min, 400 mg/Kg caused anal00 mg/Kg caused analgesia at 30 and 60 min, and 200 mg/Kg produced antinociception only at 60 min after drug injection (P < 0.05 for all the above comparisons). These results suggest that 2,5-hexanedione induces antinociception in rats. Whether this effect is mediated by a cholinergic mechanism is under inverstigation

Long-term treatment with 2,5-hexanedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adult rats

Prolonged exposure to hexacarbon compounds is neurotoxic to humans and animals. As various hexacarbon compounds inhibit glycolytic enzymes in vitro, it has been suggested that this may underlie their neurotoxic effects in vivo. in the present investigation we examined whether long-term treatment with 2,5-hexanedione (200 mg/kg, sc) for 40 days affects the specific activity of brain and liver enolase, lactic dehydrogenase and malate dehydrogenase in female Wistar rats (150-170 g). Glycemia and liver glycogen levels were also determined. The specific activity of all enzymes tested, liver glycogen content and glycemia were not affected by chronic treatment with 2,5-hexanedione. Rats treated with 2,5-hexanedione weighed significantly less than control rats starting on day 18 of treatment (183 ñ 3.4G for the vehicle groups vs 171 ñ 3.2G for the 2,5-hexanedione group). 2,5-hexanedione also increased water intake (46 por cento when compared to vehicle-treated rats). prolonged treatmentof rats with the non-neurotoxic hexacarbon 1,6-hexanediol (207 mg/kg, sc) significantly increased liver glycogen content (5.9 ñ 0.6g/100g for the vehicle group vs 9.0 ñ 1.1g/100 g for the 1.6-hexanediol group) as well as food intake (44.0 ñ 1.5g 100g-1 6 days-1 for thge 1,6-hexanediol group). These results indicate that long-term treatment with 2,5-hexanedione did not alter the brain and liver glycolytic enzymes studied, liver glycogen content or glycemia but did reduce weight gain and increased water intake, whereas the administration of the reportedly non-neurotoxic hexacarbon 1,6-hexanediol has demonstrable metabolic effects