Fig 1.
Overview of pathways that can be dysregulated by methamphetamine.
GR: glucocorticoid receptor, MR: mineralocorticoid receptor, 11β-HSD: 11β-hydroxysteroid dehydrogenase types 1 and 2, PXR: pregnane X receptor, MCP-1: Monocyte Chemoattractant Protein-1, SOD: Superoxide dismutase types 1 and 2, CYP: Cytochrome P450.
Fig 2.
Specific reactions used to determine CYP activity in the present study.
Fig 3.
Methamphetamine plasma concentration (n = 4) vs time (hours) after third methamphetamine dose.
Test drugs caffeine (metabolised by CYP1A2) and midazolam (metabolised by CYP3A) was administered 2 hours after the methamphetamine dose and plasma samples were collected 3, 4, 5, 6 and 8 hours after methamphetamine dose. Error bars represent standard error of mean (SEM).
Fig 4.
Normalised mRNA expression of hepatic drug metabolising enzyme CYP1A2 (A) between Control (n = 4) and MA (n = 4) groups. MNE, mean normalised expression; MA, methamphetamine; unpaired t test; *P<0.05 from Control.
Fig 5.
Functional activity of hepatic CYP1A2 (A) and CYP3A (B) before (Pre-MA) and after (Post-MA) methamphetamine exposure (n = 4). MA, methamphetamine; AUC, area under the curve; paired t test; *P<0.05 from Pre-MA.
Fig 6.
Normalised mRNA expression of hepatic drug transporters P-gp (A) and BCRP (B) between Control (n = 4) and MA (n = 4) groups. MNE, mean normalised expression; MA, methamphetamine; unpaired t test; *P<0.05 from Control.
Fig 7.
Normalised mRNA expression of hepatic regulators of drug transporter and metabolising enzyme regulators MR (A), GR (B), 11βHSD1 (C), 11βHSD2 (D) and PXR (E) between Control (n = 4) and MA (n = 4) groups. MNE, mean normalised expression; MA, methamphetamine; unpaired t-test; *P<0.05 from Control.
Fig 8.
Normalised mRNA expression of hepatic markers of inflammation p50 (A), p65 (B) and MCP1 (C) between Control (n = 4) and MA (n = 4) groups. MNE, mean normalised expression; MA, methamphetamine; unpaired t test; *P<0.05 from Control.
Fig 9.
Normalised mRNA expression of hepatic SOD1 (A) and SOD2 (B) between Control (n = 4) and MA (n = 4) groups. MNE, mean normalised expression; MA, methamphetamine; unpaired t test; *P<0.05 from Control.