Protective effects of apigenin on methylmercury-induced behavioral/neurochemical abnormalities and neurotoxicity in rats

• Published in: Human & experimental toxicology 2022-01, Vol.41, p.9603271221084276-9603271221084276
• Main Authors: Yadav, Rajeshwar Kumar, Mehan, Sidharth, Sahu, Rakesh, Kumar, Sumit, Khan, Andleeb, Makeen, Hafiz Antar, Al Bratty, Mohammed
• Format: Article
• Language: English
• Subjects: Abnormalities; Amyotrophic lateral sclerosis; Animals; Apigenin - metabolism; Apigenin - pharmacology; Apigenin - therapeutic use; Apoptosis; BAX protein; Bcl-2 protein; Caspase-3; Cell activation; Cell death; Cognition; Cortex (motor); Demyelination; Dimethylmercury; Flavonoids; Glial cells; Grip strength; Inflammation; Mercury (metal); Methylmercury; Methylmercury Compounds - metabolism; Methylmercury Compounds - toxicity; Motor skill learning; Myelin; Myelin basic protein; Neuronal-glial interactions; Neurons - metabolism; Neuroprotection; Neurotoxicity; Neurotoxicity Syndromes - drug therapy; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - prevention & control; Neurotoxins; Oral administration; Pathogenesis; Phenotypes; Rats; Rats, Wistar; Spinal cord; Toxins
• ISSN: 0960-3271; 1477-0903
• DOI: 10.1177/09603271221084276

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. Graphical Abstract