Journal
HUMAN & EXPERIMENTAL TOXICOLOGY
Volume 41, Issue -, Pages -Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/09603271221084276
Keywords
c-JNK; p38MAPK; methylmercury; apigenin; demyelination
Categories
Funding
- Institutional Animal Ethics Committee (IAEC) [816/PO/ReBiBt/S/04/CPCSEA, 423]
- ISFCP, Moga, Punjab, India
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This study demonstrates that APG, as a c-JNK and p38MAPK signaling inhibitor, possesses neuroprotective effects against MeHg-induced neurotoxicity. It improves neurobehavioral parameters and reduces neuroinflammation and oxidative damage.
Methylmercury (MeHg) is a neurotoxin that induces neurotoxicity and cell death in neurons. MeHg increases oligodendrocyte death, glial cell activation, and motor neuron demyelination in the motor cortex and spinal cord. As a result, MeHg plays an important role in developing neurocomplications similar to amyotrophic lateral sclerosis (ALS). Recent research has implicated c-JNK and p38MAPK overactivation in the pathogenesis of ALS. Apigenin (APG) is a flavonoid having anti-inflammatory, antioxidant, and c-JNK/p38MAPK inhibitory activities. The purpose of this study is to determine whether APG possesses neuroprotective effects in MeHg-induced neurotoxicity in adult rats associated with ALS-like neuropathological alterations. In the current study, the neurotoxin MeHg causes an ALS-like phenotype in Wistar rats after 21 days of oral administration at a dose of 5 mg/kg. Prolonged administration of APG (40 and 80 mg/kg) improved neurobehavioral parameters such as learning memory, cognition, motor coordination, and grip strength. This is mainly associated with the downregulation of c-JNK and p38MAPK signaling as well as the restoration of myelin basic protein within the brain. Furthermore, APG inhibited neuronal apoptotic markers (Bax, Bcl-2, and caspase-3), restored neurotransmitter imbalance, decreased inflammatory markers (TNF-and IL-1), and alleviated oxidative damage. As a result, the current study shows that APG has neuroprotective potential as a c-JNK and p38MAPK signaling inhibitor against MeHg-induced neurotoxicity in adult rats. Based on these promising findings, we suggested that APG could be a potential new therapeutic approach over other conventional therapeutic approaches for MeHg-induced neurotoxicity in neurobehavioral, molecular, and neurochemical abnormalities.
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