Immediate and late systemic and lung effects of inhaled paraquat in rats

Amin, Faisal Mohammad; Roohbakhsh, Ali; Memarzia, Arghavan; Kazerani, Hamid Reza; Boskabady, Mohammad Hossein

doi:10.1016/j.jhazmat.2021.125633

Cited by 20 publications

(7 citation statements)

References 32 publications

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“…It was indicated that PQ inhalation (54 mg/m 3 ), during 16 days, could effectively induce systemic inflammation and oxidative stress in male Wistar rats. 21,31 Importantly, the administration route of PQ in the current study was inhalation, which was more similar to the exposure routes of farmers. In agreement with our results, previous investigations showed that PQ increased airway resistance and tracheal responsiveness to methacholine via modifying ROS production in the lung in mice compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, inhalation of PQ aerosol (54 mg/m 3 ) induced systemic inflammation and lung injury which confirmed with body weight loss, increased tracheal responsiveness to methacholine, lung histology changes, as well as elevated TNF‐α and IL‐6 levels in the serum are supported by several previous studies. It was indicated that PQ inhalation (54 mg/m 3 ), during 16 days, could effectively induce systemic inflammation and oxidative stress in male Wistar rats 21,31 …”

Section: Discussionmentioning

confidence: 99%

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A dose‐related positive effect of inhaled simvastatin‐loaded PLGA nanoparticles on paraquat‐induced pulmonary fibrosis in rats

Shahabadi

Moshiri

Roohbakhsh

et al. 2022

Basic Clin Pharma Tox

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Objective Pulmonary fibrosis is an important complication of subacute paraquat (PQ) poisoning. Here, we reported a novel nanotherapeutic platform for PQ‐induced pulmonary fibrosis in animal inhalation models using simvastatin (SV)‐loaded into poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs). Methods and Materials Eight inhalations of normal saline, PQ (24 mg/kg), PQ plus SV (20 mg/kg), PQ plus SV‐loaded PLGA NPs at doses of 5, 10 or 20 mg/kg or PQ plus PLGA NPs were given to rats. After the end of the treatment period, inflammatory factors and creatine phosphokinase as well as lung pathological changes and tracheal responsiveness were evaluated. Results Inhalation of SV‐loaded PLGA NPs could significantly prevent the progression of PQ‐induced pulmonary fibrosis especially at a dose of 10 mg through decreasing the serum level of inflammatory factors as well as contractile responses (p < 0.001) compared to PQ group. Pathological findings also confirmed the results. However, inhalation of non‐formulated SV could not prevent tissue damage and fibrosis in comparision with SV‐loaded PLGA NPs. Conclusion Taken together, the present work provides us an idea about the pulmonary delivery of PLGA‐SV NPs using nebulizer for the treatment of PQ poisoning. However, the efficacy of this formulation in human beings and clinical use needs to be more investigated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A dose‐related positive effect of inhaled simvastatin‐loaded PLGA nanoparticles on paraquat‐induced pulmonary fibrosis in rats

Shahabadi

Moshiri

Roohbakhsh

et al. 2022

Basic Clin Pharma Tox

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“…Paraquat (1,1′‐dimethyl‐4,4′ bipyridinium dichloride) is a toxic and inexpensive bipyridylium herbicide that is widely used. Paraquat is fatal in very small amounts and provokes toxic effects on many organs such as the lungs, liver, kidney, heart, stomach, and intestine (Amin et al, 2021 ). In an animal model, EA showed a protective effect against paraquat‐induced kidney dysfunction by increasing the total antioxidant status (TAS) and decreasing the total oxidant status (TOS) (Table 3 ; Silfeler et al, 2017 ).…”

Section: Ea Against Chemicals Toxicitiesmentioning

confidence: 99%

“…One of the critical components of the non‐enzymatic antioxidant defense is GSH. GSH is a vital substance in detoxification, nutrient metabolism, cell physiology, and regulation of cellular events containing DNA and protein synthesis, apoptosis and cell proliferation, gene expression, immune response, signal transduction, and cytokine production (Amin et al, 2021 ; Ghasemzadeh Rahbardar et al, 2021 ). Several natural polyphenol compounds were established to scavenge hydroxyl radicals and superoxide anions, block lipid peroxidation, and influence processes containing free radical‐mediated injury (Ahmadi et al, 2021 ; Naraki et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

An overview on the protective effects of ellagic acid against heavy metals, drugs, and chemicals

Jamshidi,

Roohbakhsh,

Karimi

2023

Food Science & Nutrition

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Ellagic acid (EA) is a polyphenol extracted from many plants. EA modulates inflammatory mediators via antioxidant mechanisms, such as catalase (CAT) activities, superoxide dismutase (SOD), enhancement, increase in glutathione (GSH), and lipid peroxidation (LPO) suppression. EA has anti‐apoptotic properties that are thought to be mediated by regulating the expression of B‐cell lymphoma 2 (Bcl‐2), Bcl‐2‐associated X protein (Bax), and caspase‐3. In this article, we surveyed the literature dealing with the protective effects of EA against different heavy metals, drugs, and natural toxins. The findings indicated that EA has remarkable protective properties against various toxicants. Its protective effects were mostly mediated via normalizing lipid metabolism, oxidative stress, and inflammatory mediators, for example, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), and IL‐1β. The results of this study showed that EA has significant protective effects against a varied range of compounds, either chemical or natural. These effects are mainly mediated via intensifying the antioxidant defense system. However, other mechanisms such as inhibition of inflammatory responses and suppression of apoptosis are important.

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“…Therefore, improving the survival rate of patients with PQ poisoning is a medical problem seeking an urgent solution. The PQ toxicity affects many organs within the body, the lung being the primary target, manifesting as acute lung injury (ALI) or acute respiratory distress syndrome in the early stages and pulmonary fibrosis in the later stages (Dinis-Oliveira et al, 2008;Amin et al, 2021). Acute lung injury is the leading cause of death from PQ poisoning; the primary pathophysiological mechanism being the imbalances in inflammatory responses caused by the excessive immune response, leading to the inflammatory cascade effect (Subbiah and Tiwari, 2021).…”

Section: Introductionmentioning

confidence: 99%

Metformin Regulates Alveolar Macrophage Polarization to Protect Against Acute Lung Injury in Rats Caused by Paraquat Poisoning

Yuan

Hou

et al. 2022

Front. Pharmacol.

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This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.

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Immediate and late systemic and lung effects of inhaled paraquat in rats

Cited by 20 publications

References 32 publications

A dose‐related positive effect of inhaled simvastatin‐loaded PLGA nanoparticles on paraquat‐induced pulmonary fibrosis in rats

A dose‐related positive effect of inhaled simvastatin‐loaded PLGA nanoparticles on paraquat‐induced pulmonary fibrosis in rats

An overview on the protective effects of ellagic acid against heavy metals, drugs, and chemicals

Metformin Regulates Alveolar Macrophage Polarization to Protect Against Acute Lung Injury in Rats Caused by Paraquat Poisoning

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