D-ribose-L-cysteine exhibits restorative neurobehavioral functions through modulation of neurochemical activities and inhibition oxido-inflammatory perturbations in rats exposed to polychlorinated biphenyl.

Polychlorinated biphenyl (PCB) is potentially harmful environmental toxicant causing cognitive decline with depressive features. PCB-induced behavioral deficits are associated with neurochemical dysfunctions, immune changes, and oxidative stress. This study investigated the neuroprotective effects of D-ribose-L-cysteine (DRLC), a neuroprotective precursor element of glutathione on PCB-induced neurobehavioral impairments. Following the initial 15 days of PCB (2 mg/kg) exposure to rats, DRLC (50 mg/kg) was given orally for an additional 15 days, from days 16 to 30. Animals were assessed for behavioral effect such as changes in locomotion, cognition, and depression. Oxidative/nitrergic stress markers; antioxidant regulatory proteins paraoxonase-1 (PON-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nfr2), NADPH oxidase-1 (NOX-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and neuroinflammation (NF-kβ, and TNF-α); and neurochemical metabolizing enzymes (acetylcholinesterase (AChE), monoamine oxidase-A and -B (MAO-A, MAO-B)) were carried out. The PCB-induced decline in locomotion, cognitive performance, and depressive-like features were reversed by DRLC. More specifically, PCB-induced oxidative and nitrergic stress, typified by reduced levels GSH, CAT, and SOD, accompanied by elevated MDA and nitrite were attenuated by DRLC. Additionally, DRLC restored the neuroinflammatory milieu indicated by decreased NF-kβ and TNF-α levels toward normal. Hyperactivities of AChE, MAO-A, MAO-B, PON-1, and NOX-1 levels as well as Nfr2, NQO1, and PON-1 due to PCB exposure were mitigated by DLRC. Our results suggest DRLC as a prospective neurotherapeutic agent against PCB-induced neurobehavioral impairments such as cognitive deficit and depressive-like feature through antioxidative and anti-nitrergic stress, anti-neuroinflammation, inhibition of brain metabolizing enzymes, and normalization of neurochemical homeostasis.