Major component causing neurological toxicity in acute glufosinate ammonium poisoning: determination of glufosinate, 1-methoxy-2-propanol, and ammonia in serum and cerebrospinal fluid.

OBJECTIVE: To determine the primary contributor to neurotoxicity in patients with glufosinate ammonium (GLA) poisoning, by quantifying glufosinate, 1-methoxy-2-propanol, and ammonia in serum and the cerebrospinal fluid (CSF). MATERIALS AND METHODS: We collected and analysed data from confirmed cases of GLA poisoning between May 2018 and August 2020. Based on the occurrence of neurological complications (mental change, seizure, and central apnoea), patients were assigned to one of two groups: those with complications (NCx) and without (non-NCx) complications. Concentrations of glufosinate, 1-methoxy-2-propanol (1M2P), and ammonia were measured in the serum upon admission and during hospital stay. The concentrations of all these substances were again measured in the CSF following a decline in the mental status or seizure (NCx group) or on the day after hospitalisation (non-NCx group). RESULTS: Of the 20 patients included, ammonia levels in the serum and CSF at onset of altered sensorium in the NCx group (n = 16) were significantly higher than those at one day after hospitalisation in the non-NCx group (n = 4) (p = 0.011 in serum, p = 0.047 in CSF), with its concentration in the CSF being higher than that in the serum in 15/16 cases. The concentration of 1M2P was similar in the serum and CSF (8/16), but the concentrations of glufosinate (7/16) was lower in the CSF than in the serum. In the non-NCx group (n = 4), only ammonia was detectable. CONCLUSIONS: Among patients with GLA poisoning, increased CSF ammonia was significantly correlated with neurological complications.

A case of carboxyatractyloside intoxication by ingestion of the cocklebur (Xanthium strumarium) in a Korean native cow.

A 19-month-old Korean native cow died the following day after consuming new silage. Grossly, the liver showed enlargement, redness, and haemorrhages in all the lobes. Additionally, many of the bur-shaped fruits of the cocklebur (Xanthium strumarium) were found in the gastric contents. The histological evaluation confirmed centrilobular hepatic necrosis. Additionally, carboxyatractyloside (CATR), a material fatal to animals found in the cocklebur, was detected in the gastric contents using high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS). Based on the pathological findings and analytical confirmation, CATR intoxication was diagnosed. Therefore, careful feeding and elimination of the cocklebur is essential for minimising economic loss.

CCR5 knockout mice with C57BL6 background are resistant to acetaminophen-mediated hepatotoxicity due to decreased macrophages migration into the liver.

Overdose of acetaminophen (APAP) causes necrosis of centrilobular cells of the liver. Accumulating evidence suggests that innate immune system may contribute to APAP-induced hepatotoxicity. Interaction between RANTES and its receptor C-C chemokine receptor (CCR) 5 is related to recruitment of macrophages to sites of inflammation. In this study, we examined effects of CCR5 deficiency on APAP-mediated liver injury by employing CCR5 knockout (KO) mice. CCR5 wild-type (WT) and KO mice received intraperitoneal injection of APAP (300 mg/kg) and were killed 24 h after the injection. Hepatic injury was determined by using histological and biochemical analyses. Intraperitoneal APAP caused the hepatocytic necrosis, as evidenced by hematoxylin and eosin staining and an increase in alanine transaminase and aspartate transaminase levels in serum. Hepatic damage appeared to be larger in CCR5 WT animals compared with KO animals. There were no differences in cytochrome P450 2E1 between CCR5 WT and KO animals suggesting that the resistance of CCR5 KO mice did not come from alterations in APAP metabolism. Infiltration of macrophages into the liver was reduced in CCR5 KO mice, and this was accompanied decreased inflammatory responses. Inhibition of macrophage activity by pretreatment of gadolinium chloride significantly blocked APAP-caused hepatotoxicity. These results indicate that recruitment of macrophage into the inflammatory sites significantly contributes to APAP-mediated hepatocytic death and CCR5 gene deletion protects from APAP-induced liver injury by alleviating macrophage recruitment and inflammatory responses. This study represents a critical role of CCR5 in macrophage infiltration into the liver and subsequent hepatotoxicity upon challenge of APAP.