Paraquat Poisoning : Anti-Oxidants Benefits

• A wide range of therapeutic substances have been studied experimentally.
• Some have been used in humans, but most of the published work is based on single or a small number of cases (for detailed reviews see Dinis-Oliveira et al., 2008, Lock and Wilks, 2010 and Gawarammana and Buckley, 2011).
• Furthermore, most therapies have been used in combination, thereby preventing an assessment of single components.
• The following list includes agents with some experimental evidence of benefit and for which therapeutic preparations are available (doses are based on Dinis-Oliveira et al., 2008):

Anti-Oxidants

1. Vitamin E

• 300 mg twice daily p.o.
• animal models have also failed to show either a survival benefit or an improvement in histology of lungs following paraquat toxicity

2. Vitamin C

• to reduce free radical toxicity
• In the only published human study, 10 patients with paraquat poisoning with positive urine paraquat but ‘stable vital signs’, all survived after a combination of high-dose vitamin C and multiple other anti-oxidants.
• various amounts of VC (100, 500, 1000, 3000 mg/day, and 3000 mg/8 h) were given for 5 consecutive days
• It was noted that the total anti-oxidant status increased progressively with increasing doses of vitamin C

3. N-acetyl cysteine

• Despite NAC having potentially beneficial effects through multiple mechanisms (scavenging of ROS, increasing glutathione and reducing inflammation, lipid peroxidation and apoptosis), strangely it has been minimally studied in human paraquat poisoning
• 150 mg/kg over 3h; 300 mg/kg over 24 h for up to 3 weeks, to increase intracellular glutathione;

4. Desferrioxamine

• Iron enhanced toxicity of paraquat in bacteria and in mice
• No human studies have looked at the efficacy of DFO in paraquat poisoning
• 100 mg/kg over 24 hours to chelate iron which acts as catalyst in the production of hydroxyl radicals

5. Salicylic acid

• can scavenge hydroxyl radicals and inhibit the activation of NF-κB.
• no published human studies
• A single dose of sodium salicylate (200 mg kg⁻¹) to Wistar rats, 2 h after exposure to a toxic dose of paraquat (25 mg kg⁻¹) resulted in no deaths compared with 100% mortality in the control group

Recommendations:

• Several anti-oxidants have been studied in the treatment of acute paraquat poisoning, but there are insufficient data in humans to support their routine use

References:

1. PARAQUAT POISONING :A practical guide to diagnosis, first aid and medical management. Revision 8 / Draft 2016-03-22
2. Medical management of paraquat ingestion. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243009/#b99 
3. Effect of vitamin C on plasma total antioxidant status in patients with paraquat intoxication. http://www.ncbi.nlm.nih.gov/pubmed/11738270
4. www.uptodate.com