Pathophysiological Changes in Rhesus Monkeys with Paraquat-Induced Pulmonary Fibrosis

Abstract

Purpose Pulmonary fibrosis is a life-threatening lung disorder. A comprehensive understanding of the pathophysiological changes in the development of pulmonary fibrosis will lead to new insights into its treatment. Methods We used a paraquat (PQ)-induced rhesus monkey model of pulmonary fibrosis to comprehensively investigate the process of pulmonary fibrosis development. Rhesus monkeys were orally administered PQ at concentrations of 25 mg/kg, 40 mg/kg, and 80 mg/kg. The dose was given once. Behavior and clinical data, such as PQ concentration, arterial oxygen saturation, biochemical evaluation, lung histopathology, and medical imaging, were continuously observed. Results Paraquat-exposed monkeys developed pulmonary fibrosis following an expected time course, especially at 25 mg/kg. CT images showed ground-glass lesions in the lung after 4 weeks, and pulmonary fibrosis persisted until the end of follow-up. Using pathological examination, the lung sustained collagen deposition and slight inflammatory cell infiltration. All rhesus monkeys had obvious inflammatory infiltration within 1 week according to the immunohistochemical results and the number of leukocytes in the blood. The CT results showed that pulmonary fibrosis had not formed, indicating that drugs with powerful anti-inflammatory ability are potential candidates for early pulmonary fibrosis treatment. Conclusion Our study describes the dynamic process of paraquat-induced pulmonary fibrosis in rhesus monkeys and provided a pathophysiological basis for the treatment of pulmonary fibrosis. Supplementary Information The online version contains supplementary material available at 10.1007/s00408-022-00572-9.

Mechanism of action of miR-15a-5p and miR-152-3p in paraquat-induced pulmonary fibrosis through Wnt/β-catenin signaling mediation

“…Currently, animal models of pulmonary fibrosis are primarily induced using drugs ( e.g ., bleomycin or PQ) or toxins ( e.g ., silica or asbestos). The bleomycin-induced model ( Baek et al, 2020 ) is the most frequently employed; however, it has drawbacks, such as high animal mortality, complex surgical procedures, severe acute lung injury, and non-uniform lesion distribution ( Shao et al, 2022 ). Asbestos and silica are rarely utilized as inducers in animal studies because of the potential human health hazards associated with mishandling ( Shao et al, 2022 ).…”

“…In research settings, PQ exposure can be simulated using various methods such as gastric gavage or intraperitoneal injection. These models aim to replicate the damage resulting from oral, inhalation, and dermal exposure observed in clinical PQ patients ( Shao et al, 2022 ; Stevens et al, 2021 ). Animal models of PAQ-induced pulmonary fibrosis can decrease experimental animal mortality, enhance surgical success rates, and establish more suitable models for further investigation of pulmonary fibrosis ( Rychel et al, 2023 ).…”

“…Although paraquat (PQ) has been prohibited in numerous nations, it continues to be utilized in specific regions owing to its cost-effectiveness. The PQ-induced pulmonary fibrosis model has a higher success rate than other drug-induced models, making it conducive to pulmonary fibrosis research ( Shao et al, 2022 ). MicroRNAs (miRNAs) are highly conserved single-stranded small RNAs ( Barwari, Joshi & Mayr, 2016 ), operate via exosomal transport, and play a role in diverse signal transduction pathways ( He et al, 2018 ).…”

LUNG Year in Review: 2022

“…Appropriate to their significance in pulmonary medicine, interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF) were well represented in the journal. Studies of IPF investigated potential mechanisms [ 41 ], animal models of induced fibrosis [ 42 ], potential biomarkers [ 43 ] and clinical outcomes [ 44 ]. Contributions on the subject of ILD included evaluation of potential biomarkers [ 45 ], diagnostic cryobiopsy [ 24 ], pediatric ILD [ 46 ], ILD outcomes [ 47 ], as well as investigations of hypersensitivity pneumonitis [ 48 ] and bronchiectasis [ 49 , 50 ].…”

“…To that end, LUNG assigned a Deputy Editor for Basic Science Research to spearhead this effort going forward. Publications during the year included studies relevant to cigarette smoke-induced airway injury and COPD [ 12 , 13 ]; asthma [ 23 ]; pulmonary fibrosis [ 42 ]; pulmonary hypertension [ 63 ]; sarcoidosis [ 64 ]; allergic airway inflammation [ 65 ]; immunity [ 66 ]; and, acute lung injury [ 67 ].…”