The Role of Sodium Cromolyn in Treatment of Paraquat-Induced Pulmonary Fibrosis in Rat

Hemmati, Ali Asghar; Nazari, Zahra; Motlagh, Mohammad Esmaeil; Goldasteh, S.

doi:10.1016/s1043-6618(02)00122-6

Cited by 34 publications

(18 citation statements)

References 20 publications

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“…Many evidences have indicated that the mechanisms of PQ-induced PF are mainly associated with the systemic inflammatory response which is in-consistent with our results [1,5,19]. Based on our previous study, CS is one of the most successful drugs which we have tested to reduce PF in PQ toxicity [20]. In order to elucidate further mechanism by which CS may act to reduce the fibrogenic effect of PQ we examine the pathological changes in the lungs of PQ-treated rat with a focus on serum cytokines and HP content of lung tissue.…”

Section: Discussionsupporting

confidence: 91%

Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

et al. 2017

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The current study aimed to investigate the effects of Cromolyn Sodium (CS) on proinflammatory cytokines in Paraquat (PQ)-induced lung damage in rat. Animals were randomly divided into 5 groups. Group 1 and 2 received nebulized vehicle and CS (8 mg/kg) for 3 consecutive weeks, respectively. Group 3 was treated with single oral dose of PQ (40 mg/kg). Groups 4 and 5 were PQ groups which received nebulized CS (6 and 8 mg/kg/day, respectively) from 1 week before to 2 weeks after PQ administration. Finally, the animals were scarified and the changes of hydroxyproline (HP) and histology were evaluated in lung tissue. In addition, IL-1β, TNF-α and IL-8 levels were determined in serum samples. The results showed that lung HP level as well as IL-1β, TNF-α and IL-8 were significantly lower in the CS treated rats as compared to PQ group. The best response, however, was observed with the 8 mg/kg of CS as confirmed by histology findings. This study suggests that CS may prevent progression of PQ-induced lung damage by decreasing of inflammatory cytokines.

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Section: Discussionsupporting

confidence: 91%

Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

et al. 2017

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“…In the absence of these factors, newly formed capillaries are prone to rupture and can produce interstitial hemorrhages similar to those observed in our study. Furthermore, mast cells have been shown to be involved in regulating extracellular matrix and basement membrane turnover 27, 28, 29. Thus, it is conceivable that a weakness of the capillary basement membrane in the cromolyn‐treated mice could favor rupture of the new capillaries that are formed adjacent to the tumor.…”

Section: Discussionmentioning

confidence: 99%

Mast cell inhibitor cromolyn increases blood clotting and hypoxia in murine breast cancer

Samoszuk

Corwin

2003

Intl Journal of Cancer

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Human breast cancer is extensively infiltrated by mast cells that contain powerful anticoagulants such as heparin, tryptase and chymase. To determine if human breast cancer is associated with mast cell activation, we measured the levels of mast cell tryptase (an indicator of mast cell activation) in the blood of 20 women with varying stages of breast cancer. The mean level of tryptase in women with breast cancer (10.3 ؎ 4.2 g/L) was significantly higher than in 50 normal healthy women without breast cancer (3.0 ؎ 2.5 g/L, p < 0.05 by two-tailed t-test). To explore the role of mast cells in breast cancer in more detail, we then carried out experiments that were aimed at determining if an inhibitor of mast cell function, sodium cromolyn, could increase blood clotting and hypoxia within subcutaneous implants of the 4T1 mammary adenocarcinoma cell line in mice. We treated tumor-bearing mice with 5 consecutive daily doses of sodium cromolyn (10 mg/kg, i.p.). An average of 30% of the periphery of the tumors from the 5 drug-treated mice contained large lakes of clotted blood that were not evident in any of the tumors from the control (untreated) mice. By computerized image analysis of tumors immunostained for a hypoxia marker (pimonidazole), the tumors from the treated mice had significantly more hypoxia (35 ؎12 % hypoxic regions, n ‫؍‬ 5) than the tumors from untreated (control) mice (16 ؎ 7%, n ‫؍‬ 5). We conclude that sodium cromolyn enhanced peri-tumoral blood clotting and intratumoral hypoxia. These results suggest that mast cells may play an important role in regulating blood clotting and hypoxia within breast cancer.

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“…The PQ group was randomly divided into six subgroups according to the different times of examination (2,6,12,24,48 and 72 hrs), on average, after PQ treatment. Standard signs of PQ poisoning in rat models are as follows: loss of appetite, unresponsiveness, fluffy hair, rat-tail cyanosis, dyspnoea, inability to support own weight and easy to catch [27,28]. According to the different time-points, the rats were dissected after an intraperitoneal injection of sodium pentobarbital (50 mg/kg).…”

Section: Animal Modelsmentioning

confidence: 99%

HIF‐1α regulates EMT via the Snail and β‐catenin pathways in paraquat poisoning‐induced early pulmonary fibrosis

Zhu

Tan

Xie

et al. 2016

J Cellular Molecular Medi

104

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Paraquat (PQ) poisoning‐induced pulmonary fibrosis is one of the primary causes of death in patients with PQ poisoning. Hypoxia‐inducible factor‐1α (HIF‐1α) and epithelial‐mesenchymal transition (EMT) are involved in the progression of pulmonary fibrosis. Snail and β‐catenin are two other factors involved in promoting EMT. However, the relationship among HIF‐1α, Snail and β‐catenin in PQ poisoning‐induced pulmonary fibrosis is not clear. Our research aimed to determine whether the regulation of HIF‐1α in EMT occurs via the Snail and β‐catenin pathways in PQ poisoning‐induced pulmonary fibrosis. Sixty‐six Sprague–Dawley rats were randomly and evenly divided into a control group and a PQ group. The PQ group was treated with an intragastric infusion of a 20% PQ solution (50 mg/kg) for 2, 6, 12, 24, 48 and 72 hrs. A549 and RLE‐6TN cell lines were transfected with HIF‐1α siRNA for 48 hrs before being exposed to PQ. Western blotting, real‐time quantitative PCR, immunofluorescence, immunohistochemistry and other assays were used in our research. In vivo, the protein levels of HIF‐1α and α‐SMA were increased at 2 hrs and the level of ZO‐1 (Zonula Occluden‐1) was reduced at 12 hrs. In vitro, the transient transfection of HIF‐1α siRNA resulted in a decrease in the degree of EMT. The expression levels of Snail and β‐catenin were significantly reduced when HIF‐α was silenced. These data demonstrate that EMT may be involved in PQ poisoning‐induced pulmonary fibrosis and regulated by HIF‐1α via the Snail and β‐catenin pathways. Hypoxia‐inducible factor‐1α may be a therapeutic target for the treatment of PQ poisoning‐induced pulmonary fibrosis.

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The Role of Sodium Cromolyn in Treatment of Paraquat-Induced Pulmonary Fibrosis in Rat

Cited by 34 publications

References 20 publications

Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

Mast cell inhibitor cromolyn increases blood clotting and hypoxia in murine breast cancer

HIF‐1α regulates EMT via the Snail and β‐catenin pathways in paraquat poisoning‐induced early pulmonary fibrosis

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