The role of multifunctional drug therapy as an antidote to combat experimental subacute neurotoxicity induced by organophosphate pesticides.

Organophosphate pesticides are used in agriculture where they are associated with numerous cases of intentional and accidental misuse. These toxicants are potent inhibitors of cholinesterases leading to a massive build-up of acetylcholine which induces an array of deleterious effects, including convulsions, oxidative damage and neurobehavioral deficits. Antidotal therapies with atropine and oxime yield a remarkable survival rate, but fail to prevent neuronal damage and behavioral problems.

Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.

Organophosphates (OP) are highly toxic compounds that cause cholinergic neuronal excitotoxicity and dysfunction by irreversible inhibition of acetylcholinesterase, resulting in delayed brain damage. This delayed secondary neuronal destruction, which arises primarily in the cholinergic areas of the brain that contain dense accumulations of cholinergic neurons and the majority of cholinergic projection, could be largely responsible for persistent profound neuropsychiatric and neurological impairments such as memory, cognitive, mental, emotional, motor, and sensory deficits in the victims of OP poisoning. The therapeutic strategies for reducing neuronal brain damage must adopt a multifunctional approach to the various steps of brain deterioration: (i) standard treatment with atropine and related anticholinergic compounds; (ii) anti-excitotoxic therapies to prevent cerebral edema, blockage of calcium influx, inhibition of apoptosis, and allow for the control of seizure; (iii) neuroprotection by aid of antioxidants and N-methyl-d-aspartate (NMDA) antagonists (multifunctional drug therapy), to inhibit/limit the secondary neuronal damage; and (iv) therapies targeting chronic neuropsychiatric and neurological symptoms.

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat.

Aim: Although, pharmacological activation of heme oxygenase (HO)-1 has shown to produce ameliorative effects in various experimental models of inflammation, but such beneficial effects have not been observed in adjuvant-induced arthritis. Further, the upregulated activity of HO-1 has been implicated in the pathogenesis of adjuvant arthritis. The present study was designed to investigate the anti-inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar rat.