Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly with high mortality; however, there is no effective treatment, and the specific mechanism is not well understood. The antiaging protein klotho (KL) has multiple functions and exerts significant influences on various pathophysiological processes. This work evaluated the impact of KL on PQ-induced ALI and investigated its underlying mechanisms. As for in vivo research, C57BL/6 mice were treated with PQ (30 mg/kg) intraperitoneal (IP) injection to create a toxicity model of ALI (PQ group). The mice were divided into control group, KL group, PQ group, and PQ+KL group. For in vitro experiment, A549 cells were incubated with or without KL and then treated in the presence or absence of PQ for 24 h. In vivo result indicated that KL reduced the mortality, reduced IL-1β and IL-6 in the bronchoalveolar lavage fluid (BALF), attenuated ALI, and decreased apoptosis in situ. In vitro result revealed that KL significantly improved cell viability, reduced the levels of IL-1β and IL-6 in culture supernatants, suppressed cell apoptosis, inhibited caspase-3 activation, and enhanced mitochondrial membrane potential (ΔΨm) after PQ treatment. Besides, KL effectively abated reactive oxygen species (ROS) production, improved GSH content, and lowered lipid peroxidation in PQ-exposed A549 cells. Further experiments indicated that phosphorylated JNK and P38 MAPK was increased after PQ treatment; however, KL pretreatment could significantly lower the phosphorylation of P38 MAPK. Suppression of P38 MAPK improved cell viability, alleviated inflammatory response, and reduced apoptosis-related signals; however, it had no obvious effect on the production of ROS. Treatment with N-acetylcysteine (NAC), a classic ROS scavenger, could suppress ROS production and P38 MAPK activation. These findings suggested that KL could alleviate PQ-caused ALI via inhibiting ROS/P38 MAPK signaling-regulated inflammatory responses and mitochondria-dependent apoptosis.

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Background: Monensin is a commonly used veterinary antibiotic with a narrow safety range. Overdose of monensin can cause animal poisoning or even death. Monensin poisoning is rare in humans, and there is no effective detoxification protocol in clinical treatment. Objective: We report here two cases of monensin-induced rhabdomyolysis and hepatotoxicity by oral ingestion. The two patients were a couple and both were admitted to the hospital due to oral ingestion of monensin 5 days prior. Patient 1, with a past history of chronic bronchitis and hypertension, presented with severe rhabdomyolysis, hepatotoxicity, and hypoxemia. After treatment with fluid replacement and alkalinization of urine, his condition deteriorated the next day and irreversible cardiopulmonary arrest occurred. Patient 2 was diabetic and using oral hypoglycemic drugs and had obvious rhabdomyolysis from the fifth day of admission. After treatment with fluid replacement, urine alkalization, and continuous renal replacement therapy (CRRT), the patient recovered and was discharged 1 month later. Discussion: The ingestion of monensin can lead to life-threatening toxicity, with rhabdomyolysis and hepatotoxicity as the main manifestations. Comprehensive treatment including CRRT in the early stage of rhabdomyolysis may improve the condition and prognosis.