Protective effects of selenium in tacrolimus-induced lung toxicity: potential role of heme oxygenase 1

Ibrahim, Samir; El-Tahway, Nashwa; Abdalla, Ahlam M.; Khalaf, Hanaa Mohamed

doi:10.1139/cjpp-2020-0547

Cited by 6 publications

(4 citation statements)

References 88 publications

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“…Moreover, our IHC results have revealed that there is a parallel glomerular, and tubular expression pattern of Nrf2 and its target downstream proteins with nearly equivalent immunostaining reactivity, which might suggest a functional relationship. Our findings confirm the results reported by Azouz et al [ 41 ], Ibrahim et al [ 42 ], and Gao et al [ 5 ]. Oppositely, the administration of Lina significantly increased the protein expression level of Nrf2 and HO-1 in kidney tissues of TAC-treated rats, as evidenced by an increase of the area % of the immunostaining of the corresponding proteins.…”

Section: Discussionsupporting

confidence: 93%

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

Nady,

El-Raouf,

El-Sayed

2024

Mol Biol Rep

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Background Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms. Methods and results Thirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations. Conclusion Lina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

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Section: Discussionsupporting

confidence: 93%

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

Nady,

El-Raouf,

El-Sayed

2024

Mol Biol Rep

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“…Finally, we have not yet evaluated if restoring pulmonary selenoproteins with postnatal Se supplementation attenuates or prevents altered pulmonary morphometrics. In adult rodents, supplementation with dietary or intraperitoneally delivered Se decreases pulmonary markers of oxidative stress and improves acute lung injury scores after multiple oxidative and inflammatory stressors, including cecal ligation puncture, porcine circovirus type 2 infection, radiation exposure, exhaust inhalation, and tacrolimus, paraquat and aluminum chloride exposure [ 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. Future studies will explore the potential of postnatal Se repletion on impaired alveolar development in our novel animal models.…”

Section: Discussionmentioning

confidence: 99%

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development

et al. 2022

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Decreased selenium (Se) levels during childhood and infancy are associated with worse respiratory health. Se is biologically active after incorporation into Se-containing antioxidant enzymes (AOE) and proteins. It is unknown how decreased maternal Se during pregnancy and lactation impacts neonatal pulmonary selenoproteins, growth, and lung development. Using a model of neonatal Se deficiency that limits Se intake to the dam during pregnancy and lactation, we evaluated which neonatal pulmonary selenoproteins are decreased in both the saccular (postnatal day 0, P0) and early alveolar (postnatal day 7, P7) stages of lung development. We found that Se deficient (SeD) pups weigh less and exhibit impaired alveolar development compared to Se sufficient (SeS) pups at P7. The activity levels of glutathione peroxidase (GPx) and thioredoxin reductase (Txnrd) were decreased at P0 and P7 in SeD lungs compared to SeS lungs. Protein content of GPx1, GPx3 and Txnrd1 were decreased in SeD lungs at P0 and P7, whereas Txnrd2 content was unaltered compared to SeS controls. The expression of NRF-2 dependent genes and several non-Se containing AOE were similar between SeS and SeD lungs. SeD lungs exhibited a decrease in selenoprotein N, an endoplasmic reticulum protein implicated in alveolar development, at both time points. We conclude that exposure to Se deficiency during pregnancy and lactation impairs weight gain and lung growth in offspring. Our data identify multiple selenoproteins in the neonatal lung that are vulnerable to decreased Se intake, which may impact oxidative stress and cell signaling under physiologic conditions as well as after oxidative stressors.

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“…Moreover, other inflammatory factors, such as oxidative stress, may also be involved in neutrophil migration. In this study, HO‐1 concentration, a marker of oxidative stress, 21 was also measured in the lung tissue and showed a sustained dose‐dependent increase.…”

Section: Discussionmentioning

confidence: 66%

Pulmonary disorder induced by cross-linked polyacrylic acid

Higashi

Morimoto

Nishida

et al. 2022

Journal of Occupational Health

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Objectives Organic polymers are materials widely used in our daily lives, such as daily necessities, foods, and medicines. There have been reports recently that cross‐linked polyacrylic acid (CL‐PAA) can possibly cause serious lung disease. We investigated whether intratracheal instillation of CL‐PAA causes pulmonary disorder in rats. Methods Male F344 rats were administered low (0.2 mg/rat) and high (1.0 mg/rat) doses of CL‐PAA intratracheally and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses in the lungs. Only the high‐dose specimens were subjected to ultrasonic dispersion treatment of the administered material. Results There was a dose‐dependent increase in the total cell count, neutrophil count, neutrophil percentage, lactate dehydrogenase (LDH), surfactant protein D (SP‐D), cytokine‐induced neutrophil chemoattractant (CINC)‐1 and CINC‐2 values in bronchoalveolar lavage fluid (BALF) from 3 days to at least 3 months after intratracheal administration of CL‐PAA. Heme oxygenase‐1 (HO‐1) in lung tissue was also persistently elevated from 3 days to 6 months after exposure. Alkaline phosphatase (ALP) in BALF was elevated at 3 days and 1 month after exposure only in the high‐dose group. Histopathological findings in lung tissue showed inflammatory and fibrotic changes from 3 days after administration, and we observed obvious inflammatory changes for up to 3 months and fibrotic changes for up to 6 months. Conclusion Intratracheal administration of CL‐PAA induced persistent neutrophilic inflammation and fibrosis in the rats' lungs, suggesting that CL‐PAA may have inflammogenic and fibrogenic effects.

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Protective effects of selenium in tacrolimus-induced lung toxicity: potential role of heme oxygenase 1

Cited by 6 publications

References 88 publications

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

Neonatal Selenium Deficiency Decreases Selenoproteins in the Lung and Impairs Pulmonary Alveolar Development

Pulmonary disorder induced by cross-linked polyacrylic acid

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