Organophosphates (OP) produce animal damage by altering activity of neurotransmitters and by producing oxidative stress. There are over one hundred OP compounds that are insecticides. OP exposure is a common cause of toxicity in humans and animals. China is estimated to have 100,000 cases of pesticide poisoning, annually.
One OP is named Fenthion. The antioxidant, N-acetylcysteine (NAC) was studied with mice by the authors to see if it could reduce oxidative stress when used as a preventive (before Fenthion exposure) or therapeutically (after Fenthion exposure). NAC is a thiol antioxidant that increases intracellular levels of reduced glutathione, the active form.
Serum levels of glutathione (GSH), malondialdehyde (MDA), nitrites and nitrates were determined after the Fenthion exposure. Nitrite and nitrate levels are a measure of nitric oxide (NO) production, NO being an antioxidant. MDA is a measure of oxidative stress and glutathione is part of the cell’s defense system.
Serum markers of oxidative stress were increased in the mice by Fenthion and were reduced by NAC, both before and after Fenthion doses. NO levels were reduced by Fenthion and increased by NAC. GSH is necessary for many cellular functions, including DNA and protein synthesis. Low serum levels of GSH result in the buildup of oxidative damage.
CONCLUSION: Therapeutic and prophylactic N-acetylcysteine (NAC) has the ability to reduce the poisoning effects of Fenthion and NAC reduces the mortality of Fenthion poisoning. The mechanism by which NAC works is not known at this time, but could be by increasing GSH and NO as antioxidants. The mice were treated with intra-peritoneal NAC, 200 mg./kg. body weight, daily.
NOTE: Thiol antioxidants contain a sulfur and hydrogen group (-SH)and tend to have the odor of garlic. They cause the smell of a skunk and the fragrance of grapefruit.
Read about the role of NAC in treating heavy metal toxicity. Read about the toxicity of organophosphates.
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PMID: 17329844.
Summary #211.