Effects of Bryophyllum pinnatum on Dysfunctional Autophagy in Rats Lungs Exposed to Zinc Oxide Nanoparticles

Int Immunopharmacol. 2024 Nov 15:141:113005. doi: 10.1016/j.intimp.2024.113005. Epub 2024 Aug 29.

Abstract

Lung inflammation as a result of exposure to toxicants is a major pathological problem. Autophagy (AP) is a process of cell self-digestion and can be disrupted by environmental toxicants, leading to oxidative stress, inflammation and cellular damage. Bryophyllum pinnatum (Lam.) Oken has been used in folklore medicine to manage pathological abnormalities, including inflammation, but mechanisms remain unclear. This work investigated the effects of Bryophyllum pinnatum ethanol leaf extract (BP) on dysfunctional AP in the lungs of Wistar rats exposed to zinc oxide nanoparticles (ZONPs). The experimental rats were orally administered ZONPs for seven days (10 mg/kg). Some exposed rats were post-treated with BP (62.5 and 125 mg/kg) through oral gavage. Oxidative stress, inflammation, and apoptotic and autophagic parameters were assessed using biochemical assay and gene expression methods. Several indices of pulmonary damage were also evaluated. PCR analysis suggested that ZONP downregulated the expression of pro-autophagy-related genes (Beclin 2, ATG5, DAPK, and FOXP3) and upregulated the expression of the TNF-alpha, NF-Kb, LC3 and Bcl2 genes. In contrast, BP significantly (p < 0.0001) reversed ZONP-induced pulmonary toxicity and oxidative stress. It reduced MDA levels and increased SOD, CAT, GSH and GPxD activities. BP significantly (p < 0.0001) downregulated the expressions of proinflammatory genes (IL-6 and JNK) and upregulated the expressions of IL-10, CAT and SOD genes in ZONP-exposed rats. BP restored the lung's histoarchitectural structure after ZNOP-induced distortion. The results suggested that BP has antioxidant and anti-inflammatory properties, and could effectively restore ZNOP-induced dysfunctional AP in the lungs of Wistar rats.

Keywords: Antioxidant; Bryophyllum pinnatum; Lung inflammation; Oxidative stress; Zinc oxide nanoparticles.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Autophagy* / drug effects
  • Kalanchoe*
  • Lung* / drug effects
  • Lung* / immunology
  • Lung* / pathology
  • Male
  • Nanoparticles
  • Oxidative Stress* / drug effects
  • Plant Extracts* / pharmacology
  • Plant Leaves
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy
  • Pneumonia / pathology
  • Rats
  • Rats, Wistar*
  • Zinc Oxide* / toxicity

Substances

  • Zinc Oxide
  • Plant Extracts
  • Anti-Inflammatory Agents
  • Antioxidants