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Endocr Regul. 2018 Oct 1;52(4):192-198. doi: 10.2478/enr-2018-0024.

STAT3 and Nrf2 pathways modulate the protective effect of verapamil on lung injury of diabetic rats.

Author information

1
Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
2
Department of Histology, Faculty of Medicine, Minia University, 61511 Minia, Egypt.
3
Department of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt.

Abstract

OBJECTIVE:

We aimed to assess the protective role of verapamil, L-type calcium channel blockers, against early lung damage in diabetic rats. Lung injury has recently been recognized as a consequent complication of diabetes mellitus. Hyperglycemia induces inflammatory changes in lung tissue early in the disease.

METHODS:

Twenty four adult male rats were grouped into control, diabetic, diabetic treated with verapamil, and verapamil control. Streptozotocin (STZ) was used to induce diabetes. Oxidative parameters and antioxidative mechanisms were assessed in lung homogenate. Tumor necrosis factor alpha (TNFα) protein was measured as a pro-inflammatory mediator. Signal transducer and activator of transcription 3 (STAT3) gene expression and nuclear erythroid factor 2 (Nrf2) immunoexpression were screened.

RESULTS:

The lung showed oxidative damage and inflammatory infiltration in STZ diabetic rats early at 2 weeks. The parameters significantly improved in lung tissue treated with verapamil. Histopathology of the lung tissue confirmed the results. Inhibition of STAT3/TNFα pathway was involved in the protection offered by verapamil. Activation of Nrf2 together with an increasing antioxidant capacity of diabetic lung significantly ameliorates the injury induced by diabetes.

CONCLUSIONS:

Verapamil afforded protection in diabetic lung injury. The protection was mediated by the anti-inflammatory and antioxidant effects of verapamil.

KEYWORDS:

Nrf2; STAT3; TNFα; lung; streptozotocin; verapamil

PMID:
31517611
DOI:
10.2478/enr-2018-0024

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