Metallothionein‐I + II Reduces Oxidative Damage and Apoptosis after Traumatic Spinal Cord Injury in Rats

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.

Maltol Promotes Mitophagy and Inhibits Oxidative Stress via the Nrf2/PINK1/Parkin Pathway after Spinal Cord Injury

“…After SCI, spinal cord ischemia is accompanied by subsequent energy exhaustion and ATP deficiency, increasing intracellular calcium concentration and ultimately overproduction of ROS [ 32 ]. Excessive ROS formation increases the oxidative damage of proteins, DNA, and lipids molecules and promotes apoptosis-mediated cell death [ 33 ]. Our results suggested that gavage of maltol significantly promoted the expression of antioxidant-related proteins HO-1 and SOD2 in the SCI mouse models.…”

Silica nanoparticles enhance germ cell apoptosis by inducing reactive oxygen species (ROS) formation in <i>Caenorhabditis elegans</i>

“…Metallothionein is a protein with special physiological functions and plays a unique role in reducing the toxicity of heavy metals such as cadmium, nickel, and lead, as well as scavenging excessive free radicals, anti-aging, and tumor (Bhandari et al, 2017). Previous studies have shown that metallothionein can provide a stable redox environment and protect cells from oxidative stress by resisting the stress response of various organelles (Rios et al, 2018). Polak et al have shown that mtl-1 and mtl-2 play an important role in ameliorating the cytotoxicity of ZnO NPs (Polak et al, 2014).…”

Metallothioneins in Inflammatory Bowel Diseases: Importance in Pathogenesis and Potential Therapy Target

“…The local increase in MT expression is related not only to the presence of inflammation but also to decreased apoptosis and increased cell proliferation in, among others, Barrett's esophagus, tongue epithelium, and breast and colorectal cancer [ 83 ]. Rios et al demonstrated in an animal model the antiapoptotic activity of MTs due, for example, to the protective effect on exposure to oxygen free radicals in rats subjected to spinal cord injuries [ 84 ]. By virtue of the likely different immune mechanisms observed in CU and CD and hence the different intensity of apoptosis in intestinal epithelial cells in both diseases, the expression of MTs should also differ between these two groups of patients [ 9 ].…”