Effect of 2,5-hexanedione on light-molecular-weight neurofilaments (NF-L) degradation of rat nerve tissues

Abstract

To investigate the effect of 2,5-hexanedione (HD) on degradation of low-molecular-weight neurofilaments (NF-L) in nervous tissue of rats, and to explore the molecular mechanism of n-hexane neuropathy. Fifty male Wistar rats were randomly divided into one-week poisoning group (n = 10), two-week poisoning group (n = 10), three-week poisoning group (n = 10), four-week poisoning group (n = 10), and control group (n = 10). In the four poisoning groups, a rat model of n-hexane neuropathy was established by intraperitoneal injection of HD (400 mg/kg/d). The change in the sciatic nerve ultrastructure of each rat was observed under an electron microscope. The progression of HD-induced peripheral neuropathy was evaluated using a gait scoring system. The degradation rates of NF-L in the sciatic nerve and spinal cord of each rat were measured by Western Blotting. The rats showed decrease in muscle strength and abnormal gait after two weeks of HD poisoning and mild or moderate paralysis after four weeks of HD poisoning. The sciatic nerve showed degenerative change, according to electron microscope observation. Compared with the control group, the two-week poisoning group, three-week poisoning group, and four-week poisoning group had the NF-L degradation rates decreased by 25.8%, 70.4%, and 69.7%, respectively, in the supernatant fraction of sciatic nerve, and by 14.7%, 64.6%, and 67.3%, respectively, in the sediment fraction of sciatic nerve, all showing a significant difference (P < 0.01). Compared with the control group, the one-week poisoning group had the NF-L degradation rate decreased by 33.87% in the supernatant fraction of spinal cord, the four-week poisoning group had the NF-L degradation rate increased by 16.2% in the supernatant fraction of spinal cord, and the one-week poisoning group and two-week poisoning group had the NF-L degradation rates decreased by 46.3% and 13.0% in the sediment fraction of spinal cord, all showing a significant difference (P < 0.01). HD poisoning significantly inhibits NF-L degradation in the sciatic nerve, which may be associated with NF degeneration and accumulation in the axons of patients with n-hexane neuropathy.