Pulmonary Fibrosis In Wistar Rats Research Articles

Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats by Combination Treatment of Two Natural Phenolic Compounds: Quercetin and Gallic Acid

The present study aimed to investigate the protective effects of two potent natural antioxidants, gallic acid and quercetin as single or combination treatment against bleomycin-induced pulmonary fibrosis (PF). A total of 50 Wistar rats were randomly divided into 5 groups. Group 1 and 2 intratracheally received saline and bleomycin (7.5 UI/kg), respectively, on day 7, accompanied by oral saline administration for 28 day. Groups 3, 4, and 5 received a single dose of bleomycin on day 7, accompanied by oral administration of gallic acid, quercetin, and their combination, respectively, for 28 day. Finally, the lungs were removed for biochemical and histopathological tests. The combination treatment demonstrated a remarkable decrease in lung hydroxyproline and TNF-α level and increase in catalase activity as compared with both single phytochemical-treated groups. The combination treatment significantly enhanced lung SOD activity and GSH level and decreased NO and IL-6 levels as compared with quercetin-treated group. However, only combination treatment could decrease the lung index and completely reversed histopathological changes in the bleomycin-treated group. In sum, when compared to a single exposure, the combination treatment might be a more effective approach for PF treatment because of its superior efficacy in reversing lung histological changes in the bleomycin-treated group.

The Protective Effect of Naringin against Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats.

The aim of the current study was to investigate the protective effect of naringin on bleomycin-induced pulmonary fibrosis in rats. Twenty-four Wistar rats randomly divided into four groups (control, bleomycin alone, bleomycin + naringin 40, and bleomycin + naringin 80) were used. Rats were administered a single dose of bleomycin (5 mg/kg; via the tracheal cannula) alone or followed by either naringin 40 mg/kg (orally) or naringin 80 mg/kg (orally) or water (1 mL, orally) for 14 days. Rats and lung tissue were weighed to determine the lung index. TNF-α and IL-1β levels, hydroxyproline content, and malondialdehyde (MDA) levels were assayed. Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were determined. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and 0.1% toluidine blue. TNF-α, IL-1β, and MDA levels and hydroxyproline content significantly increased (p < 0.01) and GPx and SOD activities significantly decreased in bleomycin group (p < 0.01). Naringin at a dose of 80 mg/kg body weight significantly decreased TNF-α and IL-1β activity, hydroxyproline content, and MDA level (p < 0.01) and increased GPx and SOD activities (p < 0.05). Histological evidence supported the results. These results show that naringin has the potential of reducing the toxic effects of bleomycin and may provide supportive therapy for conventional treatment methods for idiopathic pulmonary fibrosis.

Evaluating the inhibitory potential of sulindac against the bleomycin-induced pulmonary fibrosis in wistar rats

The present study examined the protective effect of sulindac on bleomycin-induced lung fibrosis in rats. Animals were divided into saline group, bleomycin group (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally from day 1 to day 20). Bleomycin administration reduced the body weight, altered antioxidant status (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione) while it increased the lung weight, hydroxyproline content, collagen deposition and lipid peroxidation. However, simultaneous administration of sulindac improved the body weight, antioxidant status and decreased the collagen deposition in lungs. Moreover, the levels of inflammatory cytokine tumour necrosis factor-α increased in bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour necrosis factor-α were found reduced. Finally, histological evidence also supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The results of the present study indicate that sulindac can be used as an agent against bleomycin-induced pulmonary fibrosis.

Evaluating the Ameliorative Potential of Quercetin against the Bleomycin-Induced Pulmonary Fibrosis in Wistar Rats

The current study deals with the effect of a dietary flavanoid quercetin on fibrotic lung tissue in rats. Bleomycin was administered by single intratracheal instillation to Wistar rats to induce lung fibrosis. The pathologies associated with this included significantly reduced antioxidant capacity, ultimately leading to protracted inflammation of the lung tissue. The hallmark of this induced fibrosis condition was an excessive collagen deposition in peribronchial and perialveolar regions of the lung. Oral quercetin treatment over a period of twenty days resulted in significant reversal of the pathologies. The antioxidant defense in lung tissue was revived. Moreover, activity of the collagenase MMP-7, which was high in fibrotic tissue, was seen restored after quercetin administration. Trichome staining of lung tissue sections showed high collagen deposition in fibrotic rats, which may be a direct result of increased mobilization of collagen by MMP-7. This was appreciably reduced in quercetin treated animals. These results point towards an important protective role of quercetin against idiopathic lung fibrosis, which remains a widely prevalent yet incurable condition in the present times.

Daidzein attenuates inflammation and exhibits antifibrotic effect against Bleomycin-induced pulmonary fibrosis in Wistar rats

Among the acute and chronic lung diseases, pulmonary fibrosis (PF) is the most fatal one because of its prognosis and treatment is so far an unsuccessful task. In this study, we have used the well-known pulmonary fibrosis model, Bleomycin (BLM), to induce PF in Wistar rats. A single intratracheal instillation (3U/Kg BW) of BLM had been administered in fibrosis induced groups. The treatment drug daidzein (0.2 mg/KgBW) was administered by subcutaneous mode for 7 days. BLM administration reduces the bodyweight, antioxidant status (enzymic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and non-enzymic antioxidants such as vitamin A, vitamin C, vitamin E and reduced glutathione) whereas, it increases the lung wet to dry ratio, hydroxyproline content, collagen deposition, lipid peroxidation and myeloperoxidase. Daidzein treatment improves the body weight, enzymic and non-enzymic antioxidant status and decreases the collagen deposition in lung as confirmed by Masson's trichrome and Picro-sirius red staining. Daidzein treatment restored the lung architecture as revealed from histopathological and transmission electron microscopic studies. The levels of inflammatory cytokine Tumor necrosis factor(TNF-α) was found to be increased in BLM-induced experimental group, whereas, on treatment with daidzein expression of TNF-α was found to be reduced. The results of the present study speculate that daidzein can be used as an agent against BLM-induced pulmonary fibrosis.

An antisense oligonucleotide to HSP47 inhibits paraquat-induced pulmonary fibrosis in rats

The most common cause of death from poisoning by the widely used, but highly toxic herbicide paraquat is respiratory failure from pulmonary fibrosis, which develops through pathological overproduction of extracellular matrix proteins such as the collagens. Heat shock protein (HSP47) is a collagen-specific molecular chaperone that assists in the posttranslational modifications of procollagens during collagen biosynthesis. We investigated whether treatment with an HSP47-antisense oligonucleotide would inhibit paraquat-induced pulmonary fibrosis in Wistar rats. Rats randomized into three groups (control, paraquat, and paraquat + antisense). Paraquat (20 mg/kg/day) ( n = 16) or a saline control ( n = 10) was administered to groups of Wistar rats. Intratracheal administration of the antisense oligonucleotide (100 nmol/kg in saline) was performed after the initial paraquat treatment ( n = 16). Treatment with paraquat alone induced pulmonary fibrosis in the entire group, while treatment with the antisense oligonucleotide alone did not produce any substantial change in lung histology. Administration of antisense oligonucleotides produced a substantial reduction in paraquat-induced pulmonary fibrosis. An immunoblot analysis confirmed that the HSP47-antisense oligonucleotide inhibited HSP47 production. These findings indicate that the HSP47-antisense oligonucleotide inhibited paraquat-induced pulmonary fibrosis and pneumopathy in rats.

Evaluation of interferon-alfa 2b in a model of acute respiratory distress syndrome and pulmonary fibrosis induced by intratraqueal bleomycin in Wistar rats

2566 Background: The acute respiratory distress syndrome (ARDS) is a common clinical entity, characterized by severe and acute pulmonary dysfunction, caused by a non-cardiogenic pulmonary edema, secondary to an increased permeability in the alveolar-capillary barrier due to a local or systemic inflammatory reaction initiated and amplified by pro-inflammatory cytokines, mostly interleukin (IL) 1, 6 and 8, and TNF-α. Despite recent advances in intensive care, the mortality associated to this syndrome remains around 40–50%. Interferons are natural proteins with antiviral, antiproliferative, antiangiogenic and immunomodulatory properties. Interferon-α reduces the synthesis and deposition of collagen I and III in hepatic tissue in experimental models of hepatic fibrosis. Interferon-α also modulates inflammation by inhibiting the action of TNF-α. The objective of this study was to evaluate the effect of interferon-α 2b in an experimental model of bleomycin-induced pulmonary fibrosis in Wistar rats. Methods: We evaluated 34 Wistar rats that were anesthetized with ketamine 100 mg/kg by the intraperitoneal route and divided in two groups of 17 animals each. Both groups received an intratracheal instillation of 1,5U of bleomycin and 0,2ml of saline solution in the first day (D1). Starting on D1, Group B received subcutaneous interferon-α 2b in a dose of 100,000 U/Kg/day for 14 days. In the fifteenth day (D15), all rats in both groups were anesthetized with thiopental and sacrificed. Their right lungs medium lobes were prepared for histological evaluation. Hematoxylin eosin and picrosirius stains were performed on 4 μm cuts of each specimen under carefully controlled conditions. The areas of collagen in their lungs were quantified in (μm2) by digital image analysis with the Image Pro for Windows software. All statistical tests were two-sided, and P &lt; .05 was used to indicate statistical significance. Results: The mean pulmonary fibrosis area in the group A was 28,432 μm2 versus 8,866 μm2 in group B who used interferon-α 2b (P = 0,037). Conclusions: These results shows that the use of interferon-α 2b, in this animal model of ARDS, reduced the development of pulmonary fibrosis. No significant financial relationships to disclose.

S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis in rats

This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg) was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50, 100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC significantly reduced the increases of transforming growth factor beta, lipid peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4-induced systemic inflammation and fibrosis of lung. SAC also inhibited the decrease of thiol levels, the increase of inducible nitric oxide synthase expression, the infiltration of leukocytes, and the generation of reactive oxygen species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS according to their applied doses. These results indicate that SAC is more effective than other cysteine compounds in reducing CCl4-induced lung injury, and might be useful in prevention of interstitial pulmonary fibrosis.