Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 micromol/L), gp120 (500 pmol/L) plus ddC (50 micromol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 micromol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 micromol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 microm), whereas ddC mainly affected small diameter DRG neurons (< or =25 microm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.
Analgesics ; Animals ; Diagnosis-Related Groups* ; Ganglia, Spinal ; HIV ; Humans ; Insulin-Like Growth Factor I* ; Neuralgia ; Neurons* ; Peripheral Nervous System Diseases ; Rats ; Zalcitabine*

OBJECTIVETo assess the curative effects of different drugs on liver cell damage of rats induced by acute nickel carbonyl poisoning.

METHODSIn present study 220 SD rats were divided into control group (10 rats), carbonyl nickel group (10 rats), 20 mg/kg methylprednisolone group (40 rats), 100 mg/kg DDC group (40 rats), 10 µmol/kg sodium selenite group (40 rats), 0.25 ml shenfuhuiyangtang group (40 rats) and 20 mg/kg methylprednisolone with 100 mg/kg DDC group (40 rats). All rats except for control group inhaled passively 250 mg/m(3) carbonyl nickel for 30 minutes. At 4h and 30h after exposure, the drugs were given intraperitoneally to the rats. On the 3rd and 7th days after exposure, the liver samples were taken from 10 rats each group. The DNA damage of liver cells was detected using comet assay, the ultrastructure changes in liver cells were examined under an electronmicroscope.

RESULTSCompared to carbonyl nickel group, the tail lengths of liver cells in 5 groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05). Compared to the control group, the tail lengths of liver cells in sodium selenite and shenfuhuiyangtang groups administrated at 4h after exposure or sodium selenite, shenfuhuiyangtang and methylprednisolone with DDC groups administrated at 30h after exposure increased significantly (P < 0.05 or P < 0.01), when tested on the 3rd day after exposure. Except from methylprednisolone sub-group administrated at 4h and tested on the 7th day after exposure, the tail lengths of liver cells in other groups administrated at 4 h or 30 h and tested on the 7th day after exposure increased significantly (P < 0.05). Compared to carbonyl nickel group, the Olive moment of liver cells in 5 groups administrated at 4 h or 30 h tested on the 3rd or 7th day after exposure decreased significantly (P < 0.05 or P < 0.01). Compared to the control group, the Olive moment of liver cells in following groups (selenite and shenfuhuiyangtang groups administrated at 4 h or 30 h and tested on the 3rd or 7th day after exposure, DDC group administrated at 4 h or 30 h and tested on the 7th day after exposure, DDC group administrated at 30h and tested on the 3rd day after exposure, and methylprednisolone with DDC group administrated at 30 h and tested on the 7th day after exposure) increased significantly (P < 0.05 or P < 0.01). As compared with carbonyl nickel group, the ultrastructure observation indicated that the nucleus and other organelles of liver cells in methylprednisolone, DDC and methylprednisolone with DDC groups administrated at 4h and tested on the 3rd day were access to normal levels.

CONCLUSIONThe results of present study showed that methylprednisolone, DDC and methylprednisolone with DDC could improve obviously the repair of rat liver cell damage induced by acute carbonyl nickel poisoning, and the curative effects of early treatment were better than those of later treatment.

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; pathology ; DNA Damage ; Drugs, Chinese Herbal ; therapeutic use ; Hepatocytes ; pathology ; Male ; Methylprednisolone ; therapeutic use ; Organometallic Compounds ; poisoning ; Rats ; Rats, Sprague-Dawley ; Sodium Selenite ; therapeutic use ; Zalcitabine ; therapeutic use

No abstract available.
Lamivudine*

No abstract available.
Lamivudine*

No abstract available.
Hepatitis* ; Interferons* ; Lamivudine*

No abstract availalbe.
Hepatitis* ; Interferons* ; Lamivudine*

No abstract available.
Hepatitis, Chronic* ; Korea* ; Lamivudine*

No abstract available.
Carcinoma, Hepatocellular* ; Humans ; Lamivudine*

No abstract available.
Carcinoma, Hepatocellular* ; Humans ; Lamivudine*

No abstract availalbe.
Hepatitis* ; Interferons* ; Lamivudine*