Protective Effects of Thymoquinone, an Active Compound of Nigella sativa, on Rats with Benzo(a)pyrene-Induced Lung Injury through Regulation of Oxidative Stress and Inflammation

Molecules. 2021 May 27;26(11):3218. doi: 10.3390/molecules26113218.

Abstract

Benzopyrene [B(a)P] is a well-recognized environmental carcinogen, which promotes oxidative stress, inflammation, and other metabolic complications. In the current study, the therapeutic effects of thymoquinone (TQ) against B(a)P-induced lung injury in experimental rats were examined. B(a)P used at 50 mg/kg b.w. induced lung injury that was investigated via the evaluation of lipid profile, inflammatory markers, nitric oxide (NO), and malondialdehyde (MDA) levels. B(a)P also led to a decrease in superoxide dismutase (SOD) (34.3 vs. 58.5 U/mg protein), glutathione peroxidase (GPx) (42.4 vs. 72.8 U/mg protein), catalase (CAT) (21.2 vs. 30.5 U/mg protein), and total antioxidant capacity compared to normal animals. Treatment with TQ, used at 50 mg/kg b.w., led to a significant reduction in triglycerides (TG) (196.2 vs. 233.7 mg/dL), total cholesterol (TC) (107.2 vs. 129.3 mg/dL), and inflammatory markers and increased the antioxidant enzyme level in comparison with the group that was administered B(a)P only (p < 0.05). B(a)P administration led to the thickening of lung epithelium, increased inflammatory cell infiltration, damaged lung tissue architecture, and led to accumulation of collagen fibres as studied through haematoxylin and eosin (H&E), Sirius red, and Masson's trichrome staining. Moreover, the recognition of apoptotic nuclei and expression pattern of NF-κB were evaluated through the TUNEL assay and immunohistochemistry, respectively. The histopathological changes were found to be considerably low in the TQ-treated animal group. The TUNEL-positive cells increased significantly in the B(a)P-induced group, whereas the TQ-treated group showed a decreased apoptosis rate. Significantly high cytoplasmic expression of NF-κB in the B(a)P-induced group was seen, and this expression was prominently reduced in the TQ-treated group. Our results suggest that TQ can be used in the protection against benzopyrene-caused lung injury.

Keywords: TUNEL assay; antioxidant status; benzopyrene; immunohistochemistry; inflammatory markers; thymoquinone.

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Benzo(a)pyrene / chemistry*
  • Benzoquinones / analysis*
  • Benzoquinones / pharmacology*
  • Cholesterol / chemistry
  • DNA Fragmentation
  • Inflammation*
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipids / chemistry*
  • Lung / drug effects*
  • Lung / pathology
  • Lung Injury / chemically induced*
  • Male
  • Nigella sativa / metabolism*
  • Nitric Oxide / chemistry*
  • Oxidative Stress*
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / physiopathology
  • Rats
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antioxidants
  • Benzoquinones
  • ICAM1 protein, rat
  • IL1B protein, rat
  • Il6 protein, rat
  • Interleukin-1beta
  • Interleukin-6
  • Lipids
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Benzo(a)pyrene
  • Cholesterol
  • thymoquinone