Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity

Abstract

Objectives: The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.

Materials and methods: Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.

Results: ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (P<0.05). ILE reduced freezing and stereotyped behaviors and increased rearing responses (P<0.05). Locomotor activity also returned to control levels especially during the last hours of the experiment. ILE administration decreased the prevalence of pulmonary emphysema in the lungs (P<0.05 and P<0.01) and percentages of TUNEL positive cells in the brain (P<0.05), in comparison with the control group.

Conclusion: ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.

Keywords: Acute toxicity; Antidote; Intravenous lipid emulsion; Methamphetamine.

Figure 1

Rectal temperature of rats received methamphetamine (45mg/kg) plus intravenous lipid emulsion 20% (18.6 ml/kg). All data are expressed as mean±SEM, N=6. Comparison of data by values of zero time were analyzed by ANOVA, posttest=Tuky, N=6. # P<0.05, ## P<0.01 and$ (Not significant) compared to control group. Comparison means between groups were analyzed by non-paired T test,* P<0.05 within-group comparisons

Figure 2

Effect of methamphetamine (45 mg/kg) administration plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline on freezing and rearing in rats during different time intervals (hr). All data were expressed as mean±SEM, N=6. Comparison of values of two groups with each other at each episode of time was analyzed by non-paired T test, *P<0.05, ** P<0.01

Figure 3

Effect of methamphetamine (45 mg/kg) administration plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline on locomotor activity in rats at different time intervals (hr). Values are expressed as mean±SEM, N=6. Comparison of values of two groups with each other’s on each time was analyzed by non-paired T test, * P<0.05, ** P<0.01

Figure 4

Stereotyped behavioral response to methamphetamine (45 mg/kg) administration plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline every 10-min interval during 24 hr. Data were reported by mean±SE, N=6. Comparison of values of two groups with each other’s on each time was analyzed by non-paired T test, * P<0.05

Figure 5

Light photomicrograph of hematoxylin and eosin–stained sections in the lung tissue of rats that were exposed to methamphetamine (45 mg/kg) plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline. A) emphysema B) Bronchiolitist C) Interestitial Inflamation D) normal lung

Figure 6

Effect of methamphetamine (45 mg/kg) plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline on histopatological changes in the lung tissue of rats after 3 days. Results are shown as the mean±SEM. *P<0.05 and **P<0.01 vs control group. Data were analyzed by χ² tests. N=6

Figure 7

Immunohistochemical staining for TUNEL in the lung and brains tissue of rats that were exposed to methamphetamine (45 mg/kg) plus intravenous lipid emulsion 20% (18.6 ml/kg) or normal saline. The brain tissue from group received METH +NS (A), METH+ILE (B), and lung tissue from rats received METH +NS (C) and METH+ILE (D)

Figure 8

Effect of methamphetamine (METH) (45 mg/kg) plus intravenous lipid emulsion 20% (ILE) (18.6 ml/kg) or normal saline on cells apoptosis in the lung and brain tissues as revealed by TUNEL assay. Values are presented as mean±SEM. P<0.05* compared to control group. $= Not significant