Abstract
After spinal cord injury (SCI), some self-destructive mechanisms start leading to irreversible neurological deficits. It is known that oxidative stress and apoptosis play a major role in increasing damage after SCI. Metallothioneins I and II (MT) are endogenous peptides with known antioxidant, neuroprotective capacities. Taking advantage of those capacities, we administered exogenous MT to rats after SCI in order to evaluate the protective effects of MT on the production of reactive oxygen species (ROS) and lipid peroxidation (LP), as markers of oxidative stress. The activities of caspases-9 and -3 and the number of annexin V and TUNEL-positive cells in the spinal cord tissue were also measured as markers of apoptosis. Rats were subjected to either sham surgery or SCI and received vehicle or two doses of MT (10 μg per rat) at 2 and 8 h after surgical procedure. The results showed a significant increase in levels of MT protein by effect of SCI and SCI plus treatment at 12 h, while at 24 h an increase of MT was observed only in the injury plus treatment group (p < 0.05). ROS production was decreased by effect of MT in lesioned tissue; likewise, we observed diminished LP levels by MT effect both in the sham group and in the group with SCI. Also, the results showed an increase in the activity of caspase-9 due to SCI, without changes by effect of MT, as compared to the sham group. Caspase-3 activity was increased by SCI, and again, MT treatment reduced this effect only at 24 h after injury. Finally, the results of the number of cells positive to annexin V and TUNEL showed a reduction due to MT treatment both at 24 and 72 h after the injury. With the findings of this work, we conclude that exogenously administered MT has antioxidant and antiapoptotic effects after SCI.
Highlights
After spinal cord injury (SCI), a series of self-destructive mechanisms initiate to produce irreversible damage to the surrounding tissue, with consequent motor and sensitive deficits [1]
The mean value of rats with SCI and vehicle (SCI/SS) was 0.911 ± 0.063 (n = 10) and the value from rats with lesion plus Metallothioneins I and II (MT) (SCI/MT) was of 0.999 ± 0.055 (n = 8); both values were statistically significant as compared to the sham/SS group
Rats with SCI and vehicle (SCI/SS) showed a mean of 250.94 ± 28.35 (n = 8) and the value from rats with lesion plus MT (SCI/MT) was 325.50 ± 32.72 (n = 5); both values were statistically significant as compared to the sham/SS group
Summary
After spinal cord injury (SCI), a series of self-destructive mechanisms initiate to produce irreversible damage to the surrounding tissue, with consequent motor and sensitive deficits [1]. We evaluated the antioxidant and antiapoptotic effects of MT in a model of SCI contusion in rats
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