Effect of (-)-Delta(9)-tetrahydrocannabinoid on the hepatic redox state of mice.
(-)-Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), a psychoactive component of marijuana, has been reported to induce oxidative damage in vivo and in vitro. In this study, we administered Delta(9)-THC to healthy C57BL/6J mice aged 15 weeks in order to determine its effect on hepatic redox state. Mice were divided into 3 groups: Delta(9)-THC (N = 10), treated with 10 mg/kg body weight Delta(9)-THC daily; VCtrl (N = 10), treated with vehicle [1:1:18, cremophor EL (polyoxyl 35 castor oil)/ethanol/saline]; Ctrl (N = 10), treated with saline. Animals were injected ip twice a day with 5 mg/kg body weight for 10 days. Lipid peroxidation, protein carbonylation and DNA oxidation were used as biomarkers of oxidative stress. The endogenous antioxidant defenses analyzed were glutathione (GSH) levels as well as enzyme activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione reductase, and glutathione peroxidase (GPx) in liver homogenates. The levels of mRNA of the cannabinoid receptors CB1 and CB2 were also monitored. Treatment with Delta(9)-THC did not produce significant changes in oxidative stress markers or in mRNA levels of CB1 and CB2 receptors in the liver of mice, but attenuated the increase in the selenium-dependent GPx activity (Delta(9)-THC: 8%; VCtrl: 23% increase) and the GSH/oxidized GSH ratio (Delta(9)-THC: 61%; VCtrl: 96% increase), caused by treatment with the vehicle. Delta(9)-THC administration did not show any harmful effects on lipid peroxidation, protein carboxylation or DNA oxidation in the healthy liver of mice but attenuated unexpected effects produced by the vehicle containing ethanol/cremophor EL.
Pinto
C E
CE
Instituto de Farmacologia e Terapêutica, Universidade do Porto, Portugal.
Moura
E
E
Serrão
M P
MP
Martins
M J
MJ
Vieira-Coelho
M A
MA
D000818:Animals; D013759:Dronabinol / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000032:analysis / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D043882:Receptors, Cannabinoid / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011506:Proteins; D011619:Psychotropic Drugs; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D013759:Dronabinol