Paraquat-induced Pulmonary Fibrosis In Rats Research Articles

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

Effect of Capparis spinosa Fruit Hydroalcoholic Extract on Paraquat-Induced Pulmonary Fibrosis in the Rat.

Pulmonary fibrosis (PF) is a lethal inflammatory disease and there has been no effective medication for this progressive disease up to now. Paraquat is commonly used in agricultural settings to control weed growth and is one of the important risk factors for PF. Additionally, emerging evidence has demonstrated Capparis spinosa (C. spinose) fruit extract has anti-fibrotic, anti-inflammatory, and antioxidant properties. We aimed to evaluate whether C. spinose fruit hydroalcoholic extract has a positive effect against Paraquat-induced PF in rats. 30 male Wistar rats were randomly divided into 5 groups, which included: a control group, a Paraquat control group, a C. spinose group with a dose of 20 mg/kg, a C. spinose group with a dose of 30 mg/kg, a C. spinose group with a dose of 50 mg/kg. After 21 days of the treatment, levels of hydroxyproline and malondialdehyde (MDA) in lung tissue were assessed and lung indices and semi-quantitative histopathological changes were determined. The results showed that treatment with C. spinose, led to increased weight gain, whereas reduced lung weight.C. spinose demonstrated a decreasing effect on levels of MDA, and hydroxyproline in lung tissue. Moreover, histopathological data and the number of lung indices indicated the preventive role of C. spinose Paraquat-induced PF in rats.

Effect of bone marrow mesenchymal stem cells on paraquat-induced pulmonary fibrosis in rats

Objective: To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism. Methods: From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10(6) cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results: High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-β1, TIMP-1 levels in serum were significantly higher in PQ group (P<0.05) , while TNF-α and MMP-9 had no significant difference (P>0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-β1 in BMSC-A and BMSC-B groups were lower than those in PQ group (P<0.05) . The Lung organ coefficients, TGF-β1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference (P>0.05) . Conclusion: Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-β1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .

Human amniotic mesenchymal stem cells alleviate paraquat-induced pulmonary fibrosis in rats by inhibiting the inflammatory response

AimsTo investigate the therapeutic effects of human amniotic mesenchymal stem cells (hAMSCs) on paraquat (PQ)-induced pulmonary fibrosis in rats and investigate the inflammatory mechanisms. Main methodshAMSCs were identified by morphological, flow cytometry and immunocytochemistry. A pulmonary fibrosis model was induced by administering PQ to rats. The hAMSCs group was treated with hAMSCs after 6 h of PQ poisoning. At 21 days after hAMSCs transplantation, lungs were harvested for H&E, Masson and immunohistochemical staining to evaluate pulmonary histopathology, collagen deposition, CD3+ cell infiltration and hAMSCs colonization. Arterial blood was used for lactic acid analysis and venous blood was used to detect TNF-α, IL-6, and TGF-β1 by ELISA method. Key findingshAMSCs can improve the lung structure and decrease collagen deposition induced by PQ. The membranes of CD3+ T cell in the PQ group were round and complete, while that in the hAMSCs group rats exhibited punctate or diffuse staining. In addition, the CD3+ cell was decreased by hAMSCs administration, and MAB1281-positive cells were detected in lung of hAMSCs group rats. The survival rate of the hAMSCs group was significantly higher than that of the PQ group at 21 days after injection. TNF-α, IL-6, TGF-β1 and lactic acid were significantly decreased by hAMSCs administration. SignificancehAMSCs have a significant therapeutic effect on pulmonary fibrosis induced by acute PQ poisoning and can improve survival rate in rats. Furthermore, hAMSCs administration can improve lung histopathology and reduce collagen deposition by reducing inflammatory CD3+ T cell infiltration, inflammatory cytokine expression and lactic acid levels.

Erratum to: The Ameliorative Effects of Allopurinol on Paraquat-Induced Pulmonary Fibrosis in Rats

Erratum to: The Ameliorative Effects of Allopurinol on Paraquat-Induced Pulmonary Fibrosis in Rats

The Ameliorative Effects of Allopurinol on Paraquat-Induced Pulmonary Fibrosis in Rats

Background: Pulmonary fibrosis is described as a chronic idiopathic inflammatory disease of the interstitial lungs. It is associated with a potentially fatal prognosis, and patients show insignificant response to treatment. To treat paraquat (PQ)-induced pulmonary injury and fibrosis, multiple approaches have been used. We aimed to determine the effects of allopurinol (Allo), a xanthine oxidase inhibitor, on PQ-induced pulmonary fibrosis in rats. Methods: A total of 30 female Sprague-Dawley rats were divided randomly into five groups (200±20 g). Group 1 (control) and group 2 (PQ group) were intraperitoneally administered PQ (20 mg/kg) once on day seven without any treatment, while groups 3–5 orally received 50, 100, and 200 mg/kg of Allo seven days before and three weeks following the administration of PQ, respectively. The animals were sacrificed three weeks after PQ administration. For the histopathological analysis and assessment of serum malondialdehyde (MDA) and hydroxyproline (HP) contents, the animals’ blood and lungs were collected. Results: The PQ group showed significantly higher lung HP, serum MDA, and lung index in comparison with the control. Treatment with Allo, especially at 100 and 200 mg/kg, decreased HP, MDA, and lung index significantly, compared to the PQ group. Allo could prevent inflammatory cell infiltration, presence of fibroblasts, and PQ-related alveolar thickening. Conclusion: The results revealed that Allo has potential protective effects on PQ-related pulmonary fibrosis, and the role of xanthine oxidase in the exacerbation of PQ-induced pulmonary fibrosis was confirmed.

Effects of small RNA interference targeting mammalian target of rapamycin on paraquat-induced pulmonary fibrosis in rats

To investigate the effects of small RNA interference targeting mammalian target of rapamycin (mTOR) expression on paraquat-induced pulmonary fibrosis in rats. Human embryonic kidney cells HEK-293 were cultured in vitro. The mTOR small interfering RNA (mTOR-siRNA) expression plasmid transfection lentivirus was constructed, and non-specific sequence plasmid with no homology to mTOR gene was set as the control. Seventy-two healthy male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, paraquat model group, mTOR unrelated sequence group, and mTOR-siRNA group, with 18 rats in each group. Paraquat poisoning animal model was reproduced by intraperitoneally injecting 20% paraquat solution 15 mg/kg, while the NS control group was intraperitoneally injected the same volumes of NS. Rats in the mTOR unrelated sequence group and mTOR-siRNA group were injected 1×109 TU/mL lentivirus solution 50 μL into the airway, respectively, while in the NS control group and paraquat model group were injected the same volumes of NS. At 7, 14 and 28 days after treatment, 6 rats in each group were sacrificed respectively for lung tissue, the pathological changes and fibrosis of lung tissues were observed under light microscope. The levels of hydroxyproline (HYP) in lung tissues were determined by alkaline hydrolysis. The mRNA and protein expressions of mTOR in lung tissues were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. Under light microscope, there was no obvious pathological changes in the lung tissues in the NS control group, while in the paraquat model group and mTOR unrelated sequence group, lung tissue in rats were damaged, there were a lot of inflammatory cell infiltration, a large number of matrix collagen and fibrous tissues hyperplasia, and gradually increased with time, and it was consistent with paraquat-induced lung tissue fibrosis process. The pathological and fibrotic changes in lung tissue of mTOR-siRNA group were obviously reduced after silencing mTOR gene. The levels of HYP and the expression levels of mTOR mRNA and mTOR protein of lung tissues in the paraquat model group and mTOR unrelated sequence group were continuously increased in time-dependent manner, and they were significantly higher than those in the NS control group at all of the time points, but no significant difference was found between mTOR unrelated sequence group and paraquat model group. In mTOR-siRNA group, silencing mTOR gene could inhibit paraquat poisoning induced HYP increase in lung tissue, and the expressions increase in mTOR mRNA and mTOR protein, the values were close to the levels of NS control group, and the significant difference was found as compared with paraquat model group at 7 days or 14 days, and the change was maintained to 28 days [7 days: HYP (μg/mg) was 1.13±0.06 vs. 1.25±0.07; 14 days: HYP (μg/mg) was 1.19±0.09 vs. 1.29±0.12, mTOR mRNA (2-Δ ΔCt) was 0.99±0.11 vs. 1.94±0.12, mTOR protein (gray value) was 0.39±0.08 vs. 0.75±0.09; 28 days: HYP (μg/mg) was 1.28±0.06 vs. 1.40±0.05, mTOR mRNA (2-Δ ΔCt) was 1.15±0.13 vs. 2.85±0.15, mTOR protein (gray value) was 0.45±0.10 vs. 0.86±0.12, all P < 0.05]. Lentivirus-mediated mTOR-siRNA could effectively inhibit the expressions of mTOR in lung tissues of paraquat-poisoned rats, and reduce the damage and fibrosis of lung tissues caused by paraquat.

Effects of Rho kinase inhibitor fasudil on paraquat-induced pulmonary fibrosis in rats

Objective To investigate the effect of Rho kinase inhibitor, fasudil, on pulmonary fibrosis induced by paraquat in rats in order to elucidate the underlying mechanisms. Methods A total of 72 Sprague-Dawley male rats of specific pathogen free (SPF) were randomly(random number) divided into four groups: the normal control group (NS group, n=18), fasudil control group (FS control group, n=18), paraquat poisoning group (PQ poisoning group, n=18) and fasudil intervention group (FS intervention group, n=18). On days 7, 14, 28 after paraquat exposure, six rats were respectively selected from each group. These rats were anesthetized and sacrificed immediately, and their lung tissues were collected. The hydroxyproline (HYP) in the lung tissue was detected by using alkaline hydrolysis. The expressions of type Ⅰ, Ⅲ collagen protein, connective tissue growth factor (CTGF) and ROCK1 mRNA in Rho/ROCK signaling pathway were assayed by using the real-time quantitative PCR (RT-PCR), and the levels of type Ⅰ, Ⅲ collagen protein, connective tissue growth factor (CTGF) and Rho / ROCK signaling pathway ROCK1 protein were measured by using Western blotting. The pathological changes of lung tissue were observed under light microscope. Results There were no significant differences in the observed biomarkers between FS control group and NS group (P>0.05). While in PQ poisoning group and FS intervention group on days 7, 14, 28 (all P<0.05), the amount of HYP increased obviously (P<0.05), the expressions of type Ⅰ, Ⅲ collagen protein, CTGF, ROCK1 mRNA and protein levels were increased significantly (P<0.05). Compared with the PQ poisoning group, the amount of HYP decreased significantly, and the expressions of type Ⅰ, Ⅲ collagen protein, CTGF, ROCK1 mRNA and protein levels were decreased significantly in FS intervention group on days 7, 14, 28 (all P<0.05). The pathological changes of lung tissue revealed that the degree of pulmonary fibrosis in the PQ poisoning group were most serious on 28 d after paraquat exposure, and the degree of pulmonary fibrosis were lessened in FS intervention group on days 7, 14, 28. Conclusions ROCK inhibitor, fasudil, has obvious therapeutic effects on paraquat-induced lung fibrosis, by regulating Rho / ROCK signaling pathway with down-regulated expression of CTGF, and decrease in the levels of type Ⅰ, Ⅲ collagen protein, thus reducing protein deposition. Key words: Paraquat; Pulmonary fibrosis; Fasudil; Rho / ROCK signaling pathway

Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats.

Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-β1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-α, IL-6 and TGF-β1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti-oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content.

Docosahexaenoic acid (DHA) ameliorates paraquat-induced pulmonary fibrosis in rats possibly through up-regulation of Smad 7 and SnoN

Paraquat (PQ) poisoning has caused a large number of human fatalities due to the progressive and irreversible pulmonary fibrosis. Docosahexaenoic acid (DHA) is well-recognized as important modulators of multiple biological pathways that affect health and disease. A line of studies have shown that DHA supplementation is associated with the alleviation of some tissue fibrosis. In the current study, pulmonary fibrosis of rats was produced by a single oral dose of 50 mg/kg bw PQ treatment. Daily 500 mg/kg bw DHA supplementation was provided 7 days before PQ treatment and lasted for consecutive 35 days. DHA was found to ameliorate the pulmonary fibrotic alterations induced by PQ, which was evidenced by significant reduction of histological changes, hydroxyproline content and level of the transforming growth factor-β₁ (TGF-β₁) mRNA. Furthermore, the protein levels of Smad 7 and SnoN in the DHA supplemented rats were significantly increased compared with those in the rats of the PQ group. These results suggested that DHA ameliorated pulmonary fibrosis induced by PQ might be attributed to its enhancement of Smad 7 and SnoN expression.

Paraquat-Induced Pulmonary Fibrosis Starts at an Early Stage of Inflammation in Rats

To investigate the starting point of paraquat-induced pulmonary fibrosis in rats. A total of 96 healthy Sprague-Dawley rats were randomly divided into eight groups (n = 12 in each group) including a control and paraquat-poisoning group. Control rats received treatment with saline. Samples were collected at 2, 6, 12, 24, 48, 72 and 120 h after paraquat administered by lavage. All lung tissues were stained with hematoxylin-eosin and Masson's trichrome. Collagen III expressed in bronchoalveolar lavage fluid was detected by ELISA. The α-smooth muscle actin in lung tissue was detected by western blotting. A rat model of paraquat poisoning was established. Histological examination results indicated that lung fibrosis started in rats 2 h after paraquat poisoning. Compared with the control group, the collagen III protein in bronchoalveolar lavage fluid was significantly upregulated in the 2-h group (α = 0.05) and the same level was maintained in the other poisoning groups. The expression of α-smooth muscle actin in the lung tissue was significantly increased in the 12-h group (α = 0.05) and remained at the same level after 12 h. The paraquat-induced pulmonary fibrosis in rats began at an early stage of inflammation. The therapy of antifibrosis should be applied at an early time of paraquat poisoning.

Protective Effect of Ambroxol against Paraquat-induced Pulmonary Fibrosis in Rats

To evaluate the possible therapeutic effect of ambroxol on pulmonary fibrosis induced by paraquat. Adult male Sprague-Dawley rats (n=144, 200-250 g) were divided into four groups (Control, Ambroxol, Paraquat, and Paraquat+Ambroxol group) and sacrificed on day 1, 3, 5, 7, 14 and 28. Several significant oxidant stress markers (MDA, SOD and GSH-PX), MPO activity, cytokines (TNF-α, MCP-1, TGF-β1, MMP-2 and TIMP-1), total inflammatory cell count, hydroxyproline content, collagen I and III mRNA were analyzed. In Paraquat group, the MDA, MPO activity, hydroxyproline contents, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1, collagen I, collagen III and the number of total inflammatory cells were up-regulated in lung tissue, but SOD and GSH-PX activity were down-regulated in lung tissue compared with Control group (p<0.05). In paraquat+ambroxol group, the MDA, MPO activity, hydroxyproline content, the mRNA expression of TNF-α, MCP-1, TGF-β1, MMP-2, TIMP-1 collagen I, collagen III and the number of total inflammatory cells were significantly decreased, while the SOD and GSH-PX activities in lung tissue were increased compared with Paraquat group (p<0.05). Histological examination of paraquat-treated rats showed lung injury with interstitial edema and widespread inflammatory cell infiltration in the alveolar space and septum, as well as pulmonary fibrosis. Ambroxol could markedly reduce such damage in lung tissue and prevent pulmonary fibrosis. The results of this study indicated that ambroxol could reduce lung damage and prevent pulmonary fibrosis induced by paraquat.

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.

Antifibrotic effect of captopril and enalapril on paraquat‐induced lung fibrosis in rats

Although different treatment modalities have been implemented for pulmonary fibrosis, the results have not been promising and these conditions have been considered untreatable and irreversible. Thus, a plethora of new drugs has been tried for the control of this condition in recent years. This study examined the effects of two angiotensin-converting enzyme inhibitors, captopril and enalapril, on paraquat-induced pulmonary fibrosis in rats, through biochemical and histopathological parameters. Male albino Wistar rats were divided into eight groups (n = 4-5 each), including control, paraquat, captopril alone, captopril treatment and pre-treatment, enalapril alone, enalapril treatment and pre-treatment. After 21 days of treatment, the lungs were removed and the levels of hydroxyproline, glutathione and lipid peroxidation were determined. Angiotensin-converting enzyme inhibitors showed no effect on glutathione and lipid peroxidation. The results also demonstrated that captopril and enalapril improved pulmonary fibrosis as shown by histopathology, as well as a decreased content of hydroxyproline (P < 0.001) in the lung tissue. In conclusion, the present findings suggest that the antifibrotic effect of these drugs may be related to the inhibition of angiotensin-converting enzyme.