Berberine affords protection against oxidative stress and apoptotic damage in F1 generation of wistar rats following lactational exposure to chlorpyrifos. - GreenMedInfo Summary

Chlorpyrifos (0,0-diethyl 0-(3,5,6-trichloro-2-pyridinyl)-phosphorothioate; (CPF)) is a widely used lipophilic organophosphorus insecticide that primarily manifests into central and peripheral nervous system toxicity. However, it is poorly investigated as a developmental neurotoxicant and thus remains less explored for pharmacological interventions as well. Berberine (BBR) is a benzylisoquinoline alkaloid, primarily found in the plants of Berberidaceae family, and is used for the synthesis of several bioactive derivatives. The goal of this study was to evaluate the CPF-induced neuronal damage through lactational route and analyze the neuroprotective efficacy of berberine (BBR), a potent antioxidant compound in the F1 generation. The environmentally relevant dose of CPF (3 mg/kg b.wt.) was administered via gavage to pregnant dams from postnatal day 1 to day 20 (PND 1-20). BBR (10 mg/kg b.wt.) was administered concurrently with CPF for the same duration as a co-treatment. Levels of reactive oxygen species, lipid peroxidation, membrane bound ATPases (NaKATPase, CaATPase, and MgATPase), DNA damage, histomorphological alterations, cellular apoptosis were increased, and activities of glutathione reductase, endogenous antioxidant enzymes (SOD, CAT, GST, and GR) were decreased in cerebellum and cerebrum regions of CPF exposed pups. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. Co-treatment of BBR significantly attenuated these effects of CPF signifying oxidative stress mediated chlorpyrifos induced neuronal apoptosis. Berberine treatment ameliorated the CPF-induced downregulation of Bcl-2, Bax translocation, and up-regulation of caspase-3 in F1 pups. Therefore, BBR owing to its multiple pharmacological properties can be further explored for its therapeutic potential as an alternative neuroprotective agent against lactational exposure of chlorpyrifos-induced developmental neurotoxicity.