Triggering Mitochondrial Dysfunction and Apoptosis Under Chronic Low-dose Lambda-cyhalothrin Exposure Modulated by Melissa Officinalis L Methanol Extract in Rat Hippocampus

Abstract The extensive use of Lambda-cyhalothrin (LCT) has been associated with the various toxicities that non-target organisms can undergo including mammals. However, the mechanism of induced-LCT cytotoxicity in animal brain cells is still elusive, particularly in brain regions, notably the hippocampus, an area directly involved in cognitive function. This study aimed to investigate the neurotoxic effects in the rat hippocampus chronically exposed to LCT (0.18 mg/kg and 0.36 mg/kg), and the neuroprotective potential of Melissa officinalis L methanol extract (MOE) (200 mg/kg) against this toxicity. After experimental period (90 days), the redox status, the functional and structural integrity of the hippocampus mitochondria as well as the apoptotic signaling pathway were evaluated. The current findings suggest that LCT produces imbalance of mitochondrial redox status expressed by, on one side, increasing of stress markers such as protein carbonyls (PCO), malondialdehyde (MDA), and hydrogen peroxide (H2O2) levels; and on the other side, by a decline in the potential of antioxidant systems, namely the level of mitochondrial enzymatic activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH).This study also showed an increase in mitochondrial permeability, along with mitochondrial edema and considerable decrease in its O2 consumption. Moreover, the same results recorded an increase in caspase-3 and cytosolic cytochrome-c. Conversely, this study proved that all these toxic aspects induced by LCT were significantly mitigated when the administration of this synthetic pyrethroid was associated with MOE. Taken together, data of this study shed light on mitochondrial damage and apoptosis stimulation under the toxic effect of LCT and suggests that MOE is endowed with potent neuroprotective effect, possibly via its antioxidant and antiapoptotic properties.