The relation between oxidative stress, inflammation, and neopterin in the paraquat-induced lung toxicity

Abstract

<jats:p> Paraquat (PQ) is a well-known quaternary nitrogen herbicide. The major target organ in PQ poisoning is the lung. Reactive oxygen species (ROS) and inflammation play a crucial role in the development of PQ-induced pulmonary injury. Neopterin is synthesized in macrophage by interferon γ and other cytokines. We aimed to evaluate the utility of neopterin as a diagnostic marker in PQ-induced lung toxicity. Sprague Dawley rats were randomly divided into two groups (sham and PQ), administered intraperitoneally 1 mL saline and PQ (15 mg/kg/mL) respectively. Blood samples and lungs were collected for analyses. Lung injury and fibrosis were seen in the PQ group. Serum total antioxidant capacity, lactate dehydrogenase (LDH), and lung transforming growth factor-1β (TGF-1β) levels were significantly higher than the sham group (in all, p &lt; 0.001). In addition, in the PQ group, serum neopterin and lung malondialdehyde (MDA) levels were also significantly higher than the sham group (in all, p = 0.001). Serum neopterin levels were correlated with LDH activities, lung MDA, lung TGF-1β levels, and the degree of lung injury. These findings demonstrated that oxidative stress, reduction of antioxidant capacity, and inflammation play a crucial role in the PQ-induced lung injury. Elevated serum neopterin levels may be a prognostic parameter to determine extends of PQ-induced lung toxicity. Further studies may be performed to clarify the role of neopterin by different doses of PQ. </jats:p>

A positive feedback loop promotes HIF‐1α stability through miR‐210‐mediated suppression of RUNX3 in paraquat‐induced EMT

“…Irreversible pulmonary fibrosis leading to respiratory failure is still the main cause of PQ poisoning-induced death [23]. Oxidative stress, endoplasmic reticulum stress, inflammation and alveolar epithelial cell apoptosis are possible mechanisms of PQinduced pulmonary fibrosis [24][25][26][27]. Recent years, many studies have confirmed the role of EMT in the development of pulmonary fibrosis.…”

Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line

“…The major toxicity mechanism of PQ poisoning is production of ROS [6,31] and use of antioxidants is therefore applicable. Tan et al [32,33] demonstrated that Mel presented a potent antioxidant effect due to its ability to scavenge ROS, with better properties than vitamins C and E. This superior antioxidant capacity is attributed to the cascade reaction in which Mel participates when scavenging free radicals, involving formation of Mel metabolites that also act as radical scavengers [34].…”

PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice

“…b-actin was used as loading control cells in the lungs. Considering the fact that oxidative stress is known to play an important role in the pathogenesis of number of human inflammatory disorders including those inflicting lungs [71,72], and PARP being reported to be key mediator in such a process [73][74][75], we analyzed the levels of MDA and GSH in the lungs as markers of oxidative stress. Indeed LPS treatment in mice was found to alter redox balance as MDA level was found to be increased and conversely GSH was found to be decreased upon LPS treatment.…”