Alternative method for oral administration of insoluble toxins to rats. A prenatal study of L-mimosine.

L-mimosine is a compound found in Leucaena leucocephala, that is used as animal feed due to its high protein content, but it can also cause intoxication. Due to its low solubility in organic and aqueous solvents, its administration in laboratory animals is difficult, especially in delicate periods such as pregnancy. Thus, to circumvent such problems, this study proposes a stress-free form of oral administration with gelatin tablets with flavoring (meat broth) for 14 consecutive days of the gestational period (GD06 to GD20). For that, 17 pregnant Wistar rats divided into 3 groups were used: control (CO; n = 5) not treated; gelatin (GEL; n = 6), which received a gelatin tablet with flavoring; and gelatin with flavoring added 140 mg/kg of L-mimosine (GM; n = 6). All animals received feed and water ad libitum. The parameters analyzed were body weight gain, water and feed consumption, serum biochemistry, blood count and reproductive indices. Among these, only the real and total weight gains of dams showed statistically significant differences, with a decrease in the group GM. Thus, we could observe that flavored gelatin was an efficient and effective administration method to insoluble compounds and long-term administration to pregnant rats, with quick adaptation and without refusal by the animals. In addition, we could observe a direct effect of L-mimosine on the animals' weight gain; however, the dose administered was not sufficient to confer maternal and fetal toxicity.

Effects of Three Consecutive Days of Morphine or Methadone Administration on Analgesia and Open-Field Activity in Mice with Ehrlich Carcinoma.

This study assessed the exploratory behavioral responses in BALB/c mice inoculated with Ehrlich ascitic carcinoma after 3 consecutive days of treatment with morphine or methadone. Fifty-three female mice, 60 ± 10 d old, were used. Seven days after intraperitoneal tumor inoculation (2 × 106 cells), the animals were randomized into 7 groups: morphine 5 mg/kg (MO5), morphine 7.5 mg/kg (MO7.5), morphine 10 mg/kg (MO10), methadone 2.85 mg/kg (ME2.85), methadone 4.3 mg/kg (ME4.3), methadone 5.7 mg/kg (ME5.7), and 0.9% NaCl (Saline) (n = 7). Drug treatments were administered subcutaneously every 6 h for 3 d. The animals were evaluated for analgesia using the mouse grimace scale (MGS) and for general activity using the open field test. The MGS was performed before tumor inoculation (day 0), on day 7 at 40, 90, 150, 240, and 360 min after drug injection, and on days 8 and 9 at 40, 150, 240, and 360 min after drug injection. The open field test was performed before tumor inoculation (day 0), on day 7 after inoculation at 40, 90, 150, 240, and 360 min after drug injection, and on days 8 and 9 after inoculation at 40, 150, and 360 min after drug injection. MGS results indicated that administration of morphine promoted analgesia for up to 240 min. Conversely, methadone reduced MGS scores only at 40 min. All tested doses promoted a significant dose-dependent increase in the total distance traveled and the average speed, and increase that was markedly pronounced on days 8 and 9 as compared with day 7. The frequencies of rearing and self-grooming decreased significantly after morphine or methadone administration. Despite the difference in analgesia, both drugs increased locomotion and reduced the frequency of rearing and self-grooming as compared with the untreated control animals.