Concerns have been expressed about imidacloprid (IMI), one of the most often used pesticides,
and its potential neurotoxicity to non-target organisms. Chronic neuroinflammation is central to
the pathology of several neurodegenerative disorders. Hence, exploring the molecular mechanism
by which IMI would trigger neuroinflammation is particularly important. This study examined the
neurotoxic effects of oral administration of IMI (45 mg/kg/day for 30 days) and the potential
neuroprotective effect of Berberine chloride loaded nano-PEGylated liposomes (Ber-Lip) (10
mg/kg, intravenously every other day for 30 days) using laboratory rat. The histopathological
changes, anti-oxidant and oxidative stress markers (GSH, SOD and MDA), proinflammatory
cytokines (IL1β and TNF-α), macrophage phenotype markers (CD86 and iNOS for M1; CD163
for M2), the canonical pyroptotic pathway markers (NLRP3, caspase-1, GSDMD and IL-18) and
Alzheimer's disease markers (Neprilysin and beta amyloid (Aβ) deposits) were assessed. Oral administration of IMI resulted in apparent cerebellar histopathological alterations, oxidative stress,
predominance of M1 microglia phenotype, significantly upregulated NLRP3, caspase-1, GSDMD,
IL-18 and Aβ deposits and significantly decreased Neprilysin expression. Berberine (Ber) reduced
the IMI-induced aberrations in the measured parameters and improved the IMI-induced
histopathological and ultrastructure alterations brought on by IMI. This study highlights the IMI
neurotoxic effect and its potential contribution to the development of Alzheimer's disease and
displayed the neuroprotective effect of Ber-Lip. |
