Geranylgeranylacetone protects against morphine-induced hepatic and renal damage in mice.

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.