Effect of chronic arsenic exposure on peripheral nerve mechanical algesthesia in rats and potential protection of mecobalamin

Background Arsenic is a toxic metalloid element widely distributed in natural environment, and a primary pathway for arsenic exposure is via drinking water. Chronic arsenic exposure may cause damage to multiple organs and systems, and sensory deficits caused by peripheral neuropathies are one of the most common complications.

Objective This experiment aims to explore the effect of chronic arsenic exposure on peripheral nerve mechanical algesthesia in rats and the potential protection of mecobalamin.

Methods A total of 28 SPF SD rats were randomly divided into four groups:control group, 25 mg·L^-1 NaAsO₂ group, 100 mg·L^-1 NaAsO₂ group, and intervention group (100 mg·L^-1 NaAsO₂+ 1 mg·kg^-1 mecobalamin). The rats were exposed to arsenic by free drinking, and the rats in the intervention group was additionally given 1 mg·kg^-1·d-1 mecobalamin solution by gavage; the experiment lasted for 32 weeks. The hind foot mechanical pain threshold was measured at the 10th, 20th, and 30th weeks with Von frey filament, and the 24 h urine samples and sciatic nerve samples were collected at the end of the exposure. The expression of myelin basic protein (MBP) was detected by Western blotting, the expressions of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by immunohistochemistry, and the concentrations of arsenic metabolites in urine were detected by liquid chromatography-atomic fluorescence spectrometry.

Results At the 20th week, compared with the control group (14.67 g), the mean mechanical pain thresholds of the 25 mg·L^-1 NaAsO₂ group (9.14 g) and the 100 mg·L^-1 NaAsO₂ group (6.80 g) decreased by 38% and 54% respectively (P < 0.05), and the threshold of the intervention group (8.60 g) was higher than that of the 100 mg·L^-1 NaAsO₂ group by 27% without statistical difference. The expression levels of MBP in the 25 mg·L^-1 NaAsO₂ group (1.93±0.40) and the 100 mg·L^-1 NaAsO₂ group (2.07±0.20) were higher than that in the control group (1.00±0.20) (P < 0.05), and the expressions levels of IFN-γ and TNF-α in the 100 mg·L^-1 NaAsO₂ group (respectively 14287.98±10218.73 and 54.87±7.86) were higher than those in the control group (respectively 5 704.22±1 341.28 and 37.28±10.12) (P < 0.05). The expression level of MBP was decreased in intervention group (1.08±0.32) compared to that in the 100 mg·L^-1 NaAsO₂ group (P < 0.05), and the expression levels of IFN-γ (9 408.49±3228.92) and TNF-α (41.64±7.68) did not significantly change. The concentrations of inorganic arsenic and dimethylarsinic acid in urine were increased with higher arsenic exposure dose (P < 0.05). Compared with the 100 mg·L^-1 NaAsO₂ group(479.04±92.91) μg·L^-1, the intervention group showed a higher inorganic arsenic level(704.42±207.88) μg·L^-1 (P < 0.05).

Conclusion Chronic arsenic exposure of rats via drinking water can result in decreased mechanical pain threshold and increased expression levels of MBP and inflammatory factors (IFN-γ and TNF-α). The intervention of methylcobalamin can reduce the level of MBP, but its effect on alleviating the allodynia evoked by arsenic exposure is not obvious.