title: Geranylgeranylacetone protects against morphine-induced hepatic and             renal damage in mice.
abstract: The acute or chronic administration of opioid drugs may induce oxidative damage and cellular apoptosis in the liver and kidney, and hence result in hepatic and renal damage. Thioredoxin-1 (Trx-1) and heat shock protein 70 (Hsp70) are emerging as important modulators of cellular functions. They have been shown to be involved in cellular protective mechanisms against a variety of toxic stressors. The present study was designed to investigate the effects of geranylgeranylacetone (GGA), a pharmacological inducer of Trx-1 and Hsp70, on morphine-induced hepatic and renal damage. Morphine induced apoptosis in the liver and kidney through the mitochondria-mediated apoptosis pathway, but not the endoplasmic reticulum-mediated pathway. The activation of caspases-9 and -3 was attenuated by pre‑treatment with GGA. In addition, the morphine-induced increase of malondialdehyde (MDA) levels was suppressed by GGA. Furthermore, GGA enhanced morphine-induced expression of Trx-1 and Hsp70 in the liver and kidney. The findings of this study suggest that GGA may be a safe and novel therapeutic agent for morphine‑induced hepatic and renal damage.
authors.affiliation: Medical Faculty, Kunming University of Science and Technology,                     Kunming 650500, P.R. China.
authors.forename: Fu-Cheng
authors.initials: FC
authors.lastname: Luo
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Deng
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Xian-Si
authors.initials: XS
authors.lastname: Zeng
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009020:Morphine / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D020011:Protective Agents; D008315:Malondialdehyde; D013879:Thioredoxins; D009020:Morphine; D053148:Caspase 3; D053453:Caspase 9; C031049:geranylgeranylacetone