Diagnostic and therapeutic approach for acute paraquat intoxication

Abstract

Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.

Keywords: Antioxidants; Hemoperfusion; Paraquat; Reactive Oxygen Species.

Fig. 1

Lung is a vulnerable organ in acute paraquat intoxication. Lethal dose of paraquat (25 mg/kg) was injected intraperitoneally in mice and 3 days later, the mice were sacrificed. The lung, liver and kidney were obtained and examined by light microscopy. (A) The lung parenchyma show interstitial widening and inflammatory infiltrates predominantly in the sub-pleural area (H&E, ×40). (B) High power examination of the lung reveals dense infiltration of lymphoplasma cells (H&E, ×400). The liver (C) and kidney (D) are histologically unremarkable (H&E, ×100).

Fig. 2

ROS mediated signal transduction in inflammation. Free radicals stimulate protein complexes, such as PI3K, NF-κB, and Activator protein-1 which control transcription of DNA, involved in cellular functions such as cell growth, proliferation, and differentiation.

Fig. 3

Sequential measures on HRCT of the lung. A forty-three old woman intentionally ingested on paraquat in a suicide attempt. She presented to the hospital within 3 hr of ingestion. Serum paraquat level was 2.63 µg/mL. Note that the area of the lung lesion was not expanded in the sequential HRCT. The process of lung fibrosis completes by one month.

Fig. 4

Identification of cases with acute PQ intoxication those are treatable. The upper and lower limit of paraquat levels among survivors and non-survivors among 375 patients with acute paraquat intoxication. These levels can be divided into a dead zone (above the upper line, no survivors), gray zone (between the two lines; uncertain final outcome), and a safe zone (below the lower line, no deaths).

Fig. 5

Production of reactive oxygen species (ROS) by PQ treatment in a dose-dependent manner in Swiss 3T3. After 40 min incubation of the cells with 20-500 µM PQ, intracellular ROS generation was assessed with 2, 7-dichlorofluorescein and a laser scanning confocal microscope (×400).

Fig. 6

Antioxidant effects of thiol-containing amino acid. Note that only 10 µM of both cysteine and methionine is enough to suppress ROS formation in PQ poisoning.