Protective effects of the synthetic cannabinoids CP55,940 and JWH-015 on rat brain mitochondria upon paraquat exposure.
The effects of cannabinoids in mitochondria after acute oxidative stress insult are not fully established. We investigated the ability of CP55,940 and JWH-015 to scavenge reactive oxygen species and their effect on mitochondria permeability transition (MPT) in either a mitochondria-free superoxide anion generation system, intact rat brain mitochondria or in sub-mitochondrial particles (SMP) treated with paraquat (PQ). Oxygen consumption, mitochondrial membrane potential (Deltapsi(m)) and MPT were determined as parameters of mitochondrial function. It is found that both cannabinoids effectively attenuate mitochondrial damage against PQ-induced oxidative stress by scavenging anion superoxide radical (O(2)(*-)) and hydrogen peroxide (H(2)O(2)), maintaining Deltapsi(m) and by avoiding Ca(2+)-induced mitochondrial swelling. Understanding the mechanistic action of cannabinoids on mitochondria might provide new insights into more effective therapeutic approaches for oxidative stress related disorders.
School of Medicine, Biomedical Research Institute, University of Antioquia, Medellin, Colombia. cvelezp@quimbaya.udea.edu.co
Carlos
C
Velez-Pardo
Marlene
M
Jimenez-Del-Rio
Silvia
S
Lores-Arnaiz
Juanita
J
Bustamante
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002186:Cannabinoids / Q000737:chemistry / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology; D003511:Cyclohexanols / Q000737:chemistry / Q000494:pharmacology*; D006540:Herbicides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D016877:Oxidants / Q000378:metabolism; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D000700:Analgesics; D002186:Cannabinoids; D003511:Cyclohexanols; D006540:Herbicides; D007211:Indoles; D018696:Neuroprotective Agents; D016877:Oxidants; D013481:Superoxides; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D006861:Hydrogen Peroxide; D010269:Paraquat; D002118:Calcium; C402944:JHW 015