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<p>Cadmium (Cd), the stronger neurodegenerating heavy metal, provokes oxidative insult and disturbances in the brain. This study has been structured to investigate the neuroprotective activity of agomelatine, a specific melatonin (MT<sub>1</sub> and MT<sub>2</sub>) receptor agonist, against cadmium chloride (CdCl<sub>2</sub>)-induced toxic changes in Wistar rats. The study involved 36 animals that were arbitrarily separated into six groups <i>i.e.</i> Group I (control), Group II (Carboxymethyl cellulose-CMC- 10&#xa0;mg kg<sup>-1</sup>), Group III (agomelatine- 4&#xa0;mg kg<sup>-1</sup> alone), Group IV (CdCl<sub>2</sub>- 5&#xa0;mg kg<sup>-1</sup>), Group V and VI (CdCl<sub>2</sub> with agomelatine 2&#xa0;mg kg<sup>-1</sup> and 4&#xa0;mg kg<sup>-1</sup>). Behavioral tests for depression, learning and memory, and cerebral oxidative injury (glutathione-GSH, and thiobarbituric acid reactive substances-TBARS) were assessed. Cerebral cholinergic impairment (acetylcholinesterase-AChE) and neuroinflammation (myeloperoxidase activity and interleukin-6, 10, tumor necrosis factor-α) were determined. Protein markers of cerebral health (brain-derived neurotrophic factor-BDNF, and cAMP response element-binding protein-CREB) were estimated in the brain. CdCl<sub>2</sub>-administered animals exhibited symptoms like depression, learning and memory deficit followed by disturbed neurotransmitter level (dopamine and AChE and serotonin), reduced antioxidant status (diminished GSH and elevated TBARS), increased neuroinflammation (<i>p</i> &lt; 0.05), and downregulated the expression of BDNF and CREB. Agomelatine administration reversed the depressive behavior, and cognitive impairments. It also restored the antioxidant status, neurotransmitter levels, cerebral health and suppressed neuroinflammation. The neuroprotective effects of agomelatine on CdCl<sub>2</sub> provoked toxic effects in experimental animals’ brains, suggesting its therapeutic potential as an antioxidant and neuroprotectant agent.</p> Graphical Abstract <p></p>

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Agonism of MT1 and MT2 Receptor Mitigates Oxidative Insult, Neuroinflammation, and Cerebral Injury in Cadmium Chloride Treated Animals

  • 期刊论文

  • 发表日期：

    2025年6月10日

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  • Mani Singh Jadaun,
  • Prabhat Singh,
  • Surbhi Gupta

摘要

Cadmium (Cd), the stronger neurodegenerating heavy metal, provokes oxidative insult and disturbances in the brain. This study has been structured to investigate the neuroprotective activity of agomelatine, a specific melatonin (MT1 and MT2) receptor agonist, against cadmium chloride (CdCl2)-induced toxic changes in Wistar rats. The study involved 36 animals that were arbitrarily separated into six groups i.e. Group I (control), Group II (Carboxymethyl cellulose-CMC- 10 mg kg-1), Group III (agomelatine- 4 mg kg-1 alone), Group IV (CdCl2- 5 mg kg-1), Group V and VI (CdCl2 with agomelatine 2 mg kg-1 and 4 mg kg-1). Behavioral tests for depression, learning and memory, and cerebral oxidative injury (glutathione-GSH, and thiobarbituric acid reactive substances-TBARS) were assessed. Cerebral cholinergic impairment (acetylcholinesterase-AChE) and neuroinflammation (myeloperoxidase activity and interleukin-6, 10, tumor necrosis factor-α) were determined. Protein markers of cerebral health (brain-derived neurotrophic factor-BDNF, and cAMP response element-binding protein-CREB) were estimated in the brain. CdCl2-administered animals exhibited symptoms like depression, learning and memory deficit followed by disturbed neurotransmitter level (dopamine and AChE and serotonin), reduced antioxidant status (diminished GSH and elevated TBARS), increased neuroinflammation (p < 0.05), and downregulated the expression of BDNF and CREB. Agomelatine administration reversed the depressive behavior, and cognitive impairments. It also restored the antioxidant status, neurotransmitter levels, cerebral health and suppressed neuroinflammation. The neuroprotective effects of agomelatine on CdCl2 provoked toxic effects in experimental animals’ brains, suggesting its therapeutic potential as an antioxidant and neuroprotectant agent.

Graphical Abstract