Kidney and lung injury in rats following acute diquat exposure

Abstract

Diquat (1,1'-ethylene-2,2'-bipyridylium) is a type of widely used agricultural chemical, whose toxicity results in damage to numerous tissues, including the lung, liver, kidney and brain. The aim of the present study was to establish a rat model of acute diquat exposure and explore the relationship between diquat concentration, and kidney and lung injury, in order to provide an experimental basis for clinical treatment. A total of 140 healthy adult male Wistar rats were randomly divided into control and exposure groups. The diquat solution was administered intragastrically to the exposure group at 1/2 of the lethal dose (140 mg/kg). An equal volume of water was administered to the control group. The dynamic changes in the plasma and tissue diquat levels were quantitatively determined at 0.5, 1, 2, 4, 8, 16 and 24 h following exposure using liquid chromatography mass spectrometry. The content of hydroxyproline (HYP) in the lung tissues, as well as the levels of blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), kidney injury molecule-1 (KIM-1) and tumor growth factor (TGF)-β1, were detected using western blot analysis at every time point. Lung and kidney morphology were also assessed. Electron microscopy showed that the degree of renal damage gradually increased with time. Vacuolation gradually increased, some mitochondrial bilayer membrane structures disappeared and lysosomes increased. The lung tissue damage was mild, and the cell membrane integrity and organelles were damaged to varying degrees. The plasma and organ levels of diquat peaked at ~2 h, followed by a steady decrease, depending on the excretion rate. Over time, the serum concentrations of UA, BUN, Cr and KIM-1 were all significantly increased (P<0.05). Serum KIM-1 in rats was increased after 0.5 h, and was significantly increased after 4 h, suggesting that KIM-1 is an effective predictor of early renal injury. Early TGF-β1 expression was clearly observed in renal tissue, while no clear TGF-β1 expression was observed in the lung tissue. In conclusion, the concentration of diquat in the serum and tissue of rats with acute diquat poisoning peaked at an early stage and then rapidly decreased. The renal function damage and pathological changes persisted, the lung tissue was slightly damaged with inflammatory cell infiltration, and early pulmonary fibrosis injury was not obvious.

Case series: Diquat poisoning with acute kidney failure, myocardial damage, and rhabdomyolysis

“…In this case report, diquat concentration in the blood was reduced via hemoperfusion and hemofiltration. Previous studies reported a higher concentration of diquat in the liver, brain, kidney, and skeletal muscles than in the blood in the early stages of poisoning (1,11,16). Thus, we hypothesized that hemoperfusion and hemofiltration eliminate poisons in tissues at a lower rate than that in blood.…”

“…Patients with severe cases may develop acute kidney injury, as noted in the present cases, as diquat accumulates in high concentrations in the kidneys ( 1 ). Animal studies demonstrate that diquat can easily cause edema, degeneration, and necrosis of the renal tubules ( 11 ). Major pathological changes observed on autopsy include congested kidneys, necrotic renal tubules, and intact glomeruli ( 12 , 13 ).…”

“…Jović-Stosić et al ( 5 ) reported on a 35-year-old woman with significant elevation of transaminase levels after ingesting diquat, but her liver only showed congestion at autopsy. Wu et al ( 11 ) reported acute tubular injury and minimal pathological findings in the liver of diquat-intoxicated rats. Jones et al ( 16 ) had hypothesized that diquat-induced liver injury is typically mild, transient, and resolves spontaneously.…”

Identification of A Novel Signature for Predicting the Prognosis of Patients with Diquat Poisoning

“…The Scr is an important response index of acute renal failure (29). As a risk factor for QD poisoning, the trend of Scr deterioration in DQ poisoning death group was significantly higher than that in survival group, and had a significant negative correlation with survival time, suggesting that Scr could reflect the severity and prognosis of DQ poisoning (30).…”

Clinical and pathological characteristics of diquat poisoning-related acute kidney injury

“…Unlike paraquat, diquat seldom causes pulmonary fibrosis, at least during a short period or at the early stage. In one study, it only caused infiltration of inflammatory cells, resulting in a diffuse exudative change in both lung fields [ 8 ]. However, differential diagnosis or underdiagnosis might lead to inefficient therapy, which might cause the patient to develop pulmonary fibrosis and result in respiratory failure, causing death.…”