Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200–240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.

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1 The N-acetylation of dapsone (DDS) was studied in 108 unrelated Chinese subjects residing in the mainland of China. 2 The frequency of slow acetylators determined using the plasma monoacetyldapsone to DDS ratio (MADDS/DDS, slow acetylators < 0.30 and rapid acetylators > 0.35) at 3 h after an oral dose of DDS (100 mg) was 13.0% (14 of the 108 subjects) with a 95% confidence interval of 7.9 to 20.6%. 3 The mean plasma concentration of MADDS was about three times lower in the slow than in the rapid acetylators and there was a highly significant correlation (r, = 0.886, P < 0.001) between plasma MADDS concentration and acetylation ratio. 4 Urinary acetylation ratios (MADDS/DDS) and cumulative urinary excretion of MADDS were significantly (P < 0.001) lower in slow acetylators compared with rapid acetylators. In addition, there was a significant relationship (rs = 0.510 to 0.718, P < 0.001) between plasma and urinary acetylation ratios. However, the distribution of the urinary acetylation ratio was not bimodal. 5 The urinary acetylation ratio after an oral dose of DDS is not a discriminative index for determining acetylation phenotype.

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