Manganese Exposure Induces Mild Behavioral and Histological Deficits in Wistar Rats: Ameliorative Effects of D-ribose-L-cysteine

Heavy metal exposure is a global health problem and their presence in our environment has been greatly increased by industrial activities over the past century. Manganese is an essential trace metal in the body. However, exposure to elevated levels is neurotoxic, leading to manganism, a Parkinsonian-like syndrome. In the present study, we investigated the effects of D-ribose-L-cysteine on behavioral and histological changes in key brain regions (including, the hippocampus, cortex, striatum, and cerebellum) in rats following manganese treatment. Thirtytwo adult rats were administered either saline (control), manganese (25 mg/kg intraperitoneally for 15 days at 48 hour intervals in 8 doses), D-ribose-L-cysteine (200 mg/kg, orally for 2 weeks), and manganese (Mn) and Dribose-L-cysteine co-administration. At the end of the administration, behavioral and histological studies were performed. The Y-maze, elevated plus maze (EPM), and open field test (OFT) were used for neurobehavioral evaluation. Thereafter, brains were excised and processed for histological assessment via routine hematoxylin and eosin staining. Results revealed only mild behavioural change following manganese exposure documented by alterations in grooming frequency as seen in the Mn-only group. Nevertheless, the behavioural change noted here was attenuated by D-ribose-L-cysteine treatment evident in the manganese and D-ribose-L-cysteine coadministration group. Histological evaluation showed cytoarchitectural alterations following manganese exposure presented as pyknosis, vacuolations, and loss of cerebellar Purkinje cells. D-ribose-L-cysteine administration mitigated the observed manganese-induced distortions of neuronal architecture. These findings indicate that Dribose-L-cysteine could improve anxiety-related behavioural deficits and maintain neuronal architecture thereby preventing potential physiological impairments in manganese-induced neurotoxicity.

Key Words: manganese, D-ribose-L-cysteine, neurotoxicity, behavior, histology