Protective effects of Nigella sativa L. seed extract on lead induced neurotoxicity during development and early life in mouse models

Abstract

Lead (Pb), a ubiquitous heavy metal and a known neurotoxicant, produces adverse effects on the brain via increased production of reactive oxygen species (ROS) and causes oxidative stress. In this study we examined the neuroprotective effects of the ethanolic extract of Nigella sativa L. seeds on Pb induced oxidative stress in the developing brain of mice. Mouse pups were exposed to low (0.1%) and high (0.2%) doses of Pb from the first day of pregnancy through their mothers (via drinking water) and lactation until post-natal day (PND) 21. The mRNA expression levels of superoxide dismutase (SOD1), peroxiredoxin (Prdx6), amyloid precursor protein (APP) common, APP695 and APP770 were examined in the cortex and hippocampus of the mouse brain excised on PND 21 by semi-quantitative RT-PCR. The free radical scavenging activity of ethanolic Nigella sativa L. extract was assessed by DPPH assay. The results showed that Pb exposure caused a significant decrease in the expression of SOD1, Prdx6 and APP695 and an increase in APP770 in both cortex and hippocampus in a dose dependent manner as compared to the control group. The expression of APP common remained unaltered. Histological assessment of the cortex and hippocampus demonstrated a decrease in the neuronal number and Nissl bodies. The administration of 250 and 500 mg kg⁻¹ ethanolic Nigella sativa L. extract reversed the adverse effects by significantly increasing the expression of SOD1, Prdx6 and APP695 and decreasing the expression of APP770 in both the regions. These results strongly suggest that Nigella sativa L. supplementation greatly improves Pb-induced neurotoxicity in early life and provides neuroprotective and antioxidant potentials.