The effect of different drugs on hard metal lung disease in a rat model

Toxicol Ind Health. 2022 Feb;38(2):92-99. doi: 10.1177/07482337211062973. Epub 2022 Feb 22.

Abstract

Hard metal lung disease (HMLD) drugs include dexamethasone sodium phosphate (Dex), methylprednisolone (MP) injection, N-acetylcysteine injection (NAC), and a mix of Dex, MP, and NAC (MIX). In this study, we compared the effects of these drugs on different cytokines of hard metal lung disease in a rat model. Thirty-six adult female Sprague Dawley rats were distributed equally into the control group, hard metal (HM) group, Dex group, MP group, NAC group, and MIX group. HM powder (0.5 mL, 20 mg/mL; one time) was administered by intraperitoneal injection to the HM group through the pulmonary endotracheal tube, while the control group received normal saline (0.5 mL, 20 mg/mL; one time). After 4 weeks, the drugs were administered to the experimental groups (0.5 mL, 20 mg/mL; one time). After 8 weeks, bronchoalveolar lavage fluid (BALF) and serum were examined for cytokine levels. Biochemical analysis indicated that the Dex, MP, NAC, and MIX did not improve TGF-β1, TGF-β2, KL-6, and MMP-1 in the BALF, while MIX increased TIMP-1 in BALF. In addition, the NAC treatment significantly increased the expression levels of TGF-β1, TGF-β2, KL-6, and MMP-1. The MIX treatment significantly increased the expression levels of TGF-β1, TGF-β2, and KL-6. The MP treatment significantly increased the expression levels of KL-6, and MMP-1. The Dex treatment significantly increased the expression levels of TGF-β1, KL-6, and MMP-1. This study demonstrated that administered with NAC and MIX could improve TGF-β1, TGF-β2, and KL-6 in serum of hard metal lung disease in a rat model. Therefore, NAC injection may be considered a useful candidate in the development of a preventive agent against HMLD.

Keywords: Hard metal lung disease; bronchoalveolar lavage fluid; cytokine; pulmonary fibrosis; the effect of different drugs.

MeSH terms

  • Alloys
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Cobalt
  • Female
  • Lung Diseases*
  • Lung*
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta1 / metabolism
  • Tungsten

Substances

  • Alloys
  • Transforming Growth Factor beta1
  • hard metal
  • Cobalt
  • Tungsten