Vitamin D treatment abrogates the inflammatory response in paraquat-induced lung fibrosis

Toxicol Appl Pharmacol. 2018 Sep 15:355:60-67. doi: 10.1016/j.taap.2018.06.020. Epub 2018 Jun 23.

Abstract

A high incidence of intentional or accidental paraquat (PQ) ingestion is related to irreversible lung fibrosis and no effective therapy is currently available. Vitamin D has emerged with promising results as an immunomodulatory molecule when abrogating the inflammatory responses of lung diseases. Therefore, we have investigated the role of vitamin D treatments on PQ-induced lung fibrosis in male C57/BL6 mice. Lung fibrosis was induced by a single injection of PQ (10 mg/kg; i.p.). The control group received PQ vehicle. Seven days later, after the PQ injection or the vehicle injection, the mice received vitamin D (5 μg/kg, i.p., once a day) or vehicle, for a further 7 days. Twenty-four hours after the last dose of vitamin D or the vehicle, the analysis were performed. The vitamin D treatments reduced the number of leukocytes in their BALF and they decreased the IL-6, IL-17, TGF-beta and MMP-9 levels and the abrogated collagenase deposits in their lung tissues. Conversely, the vitamin D treatments increased the resolvin D levels in their BALF. Moreover, their tracheal contractility was also significantly reduced by the vitamin D treatments. Altogether, the data that was obtained showed a promising use of vitamin D, in treating the lung fibrosis that had been induced by the PQ intoxications. This may improve its prognostic use for a non-invasive and low cost therapy.

Keywords: Collagen Production; Cytokines; Lung fibrosis; Metalloproteinases; Paraquat intoxication; Tracheal responsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Collagen / biosynthesis
  • Cytokines / metabolism
  • Herbicides / toxicity*
  • Inflammation / chemically induced
  • Inflammation / prevention & control*
  • Leukocyte Count
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction / drug effects
  • Paraquat / antagonists & inhibitors*
  • Paraquat / toxicity*
  • Pulmonary Edema / prevention & control*
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / prevention & control*
  • Vitamin D / therapeutic use*
  • Vitamins / therapeutic use*

Substances

  • Cytokines
  • Herbicides
  • Vitamins
  • Vitamin D
  • Collagen
  • Paraquat

Supplementary concepts

  • Paraquat lung