Morphine pre- and post-conditioning exacerbates apoptosis in rat hippocampus cells in a model of homocysteine-induced oxidative stress

Introduction. Recent investigations indicated that morphine has protective effects in different ischemia/reperfusion models and may protect against neuronal cell death, while other evidence showed that morphine induces apoptosis in neurons. Therefore, the current study was conducted to investigate pre- and post-conditioning effects of morphine on hippocampal cell apoptosis in a rat model of homocysteine (Hcy)-induced oxidative stress.Methods. In the present study, 0.5 μmol/μl Hcy was injected into bilateral intrahipocampal in the rat brain and morphine at a therapeutic dose of 10 mg/kg was injected intraperitoneally 5 days before and after Hcy injection in rats. The left and right rat hippocampus were removed for biochemical and histopathological analysis. In addition, hippocampal cell apoptosis was assayed by the TUNEL kit.Results.Our results indicated that malondialdehyde (MDA) and superoxide anion (SOA) levels in the Hcy group were increased significantly compared to the control group (P<0.001). In addition, morphine pre-and post-treatment increased the MDA and SOA levels significantly in rat hippocampus compared with other groups (P<0.001). It was found that Hcy alone induced apoptosis in hippocampus cells and significantly increased the number of TUNEL-positive cells in rat hippocampus compared to the other group (P<0.001). Notably, our results indicated that pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group (P<0.001).Discussion. In conclusion, morphine neuroprotection and neurotoxicity needs to be further investigated to determine morphine side-effects in medical applications and to identify new targets for potential therapies. Our results have demonstrated that morphine pre- and post-treatment could not decrease TUNEL-positive cells in rat hippocampus cells. On the other hand, pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group. Contrast to our results, previous studies suggested neuroprotective effects of morphine against neuronal cell death. It can be hypothesized that these apoptotic effects may be attributed to effects of opioids on neuronal structure (cytoskeleton), which can lead to neuronal damage. Taken together, our data suggested that morphine pre- and post-conditioning exacerbates apoptosis and oxidative stress in hippocampus cells.Introduction. Recent investigations indicated that morphine has protective effects in different ischemia/reperfusion models and may protect against neuronal cell death, while other evidence showed that morphine induces apoptosis in neurons. Therefore, the current study was conducted to investigate pre- and post-conditioning effects of morphine on hippocampal cell apoptosis in a rat model of homocysteine (Hcy)-induced oxidative stress.Methods. In the present study, 0.5 μmol/μl Hcy was injected into bilateral intrahipocampal in the rat brain and morphine at a therapeutic dose of 10 mg/kg was injected intraperitoneally 5 days before and after Hcy injection in rats. The left and right rat hippocampus were removed for biochemical and histopathological analysis. In addition, hippocampal cell apoptosis was assayed by the TUNEL kit.Results.Our results indicated that malondialdehyde (MDA) and superoxide anion (SOA) levels in the Hcy group were increased significantly compared to the control group (P<0.001). In addition, morphine pre-and post-treatment increased the MDA and SOA levels significantly in rat hippocampus compared with other groups (P<0.001). It was found that Hcy alone induced apoptosis in hippocampus cells and significantly increased the number of TUNEL-positive cells in rat hippocampus compared to the other group (P<0.001). Notably, our results indicated that pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group (P<0.001).Discussion. In conclusion, morphine neuroprotection and neurotoxicity needs to be further investigated to determine morphine side-effects in medical applications and to identify new targets for potential therapies. Our results have demonstrated that morphine pre- and post-treatment could not decrease TUNEL-positive cells in rat hippocampus cells. On the other hand, pre- and post-treatment by morphine increased apoptosis in hippocampus cells compared with the other group. Contrast to our results, previous studies suggested neuroprotective effects of morphine against neuronal cell death. It can be hypothesized that these apoptotic effects may be attributed to effects of opioids on neuronal structure (cytoskeleton), which can lead to neuronal damage. Taken together, our data suggested that morphine pre- and post-conditioning exacerbates apoptosis and oxidative stress in hippocampus cells.

Keywords:

Homocysteine , Morphine , Tunel , Apoptosis