Inhibitory activity of flaxseed oil against CdCl2 induced liver and kidney damage: Histopathology, genotoxicity, and gene expression study

Autor: Emad M. Hassan, Noha E. Ibrahim, Kawthar A Diab, Maha A. Fahmy, Enayat A. Omara
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Toxicology Reports
Toxicology Reports, Vol 7, Iss, Pp 1127-1137 (2020)
ISSN: 2214-7500
Popis: Graphical abstract
Highlights • CdCl2 induced severe histological and genetic lesions in mouse liver and kidney. • Flaxseed oil successfully repaired hepatic and renal histological lesions induced by CdCl2. • Flaxseed oil effectively decreased comet tail formation induced by CdCl2 in mouse liver and kidney. • Flaxseed oil significantly downregulated relative mRNA expression levels of TNF-α and p53 in mouse liver. • Flaxseed oil remarkably downregulated immunohistochemical expression of caspase-9 in liver and kidney.
The present work evaluated the effect of flaxseed oil (FO) against toxicity induced by cadmium chloride (CdCl2) in the mouse liver and kidney. Male Swiss albino mice were treated with CdCl2 (4.5 mg/kg, intraperitoneally) with or without FO at three concentrations (4, 8, 12 mL/kg, orally) for two consecutive weeks. To analyze the effects of FO, we used the following techniques: (1) histopathological examination; (2) comet assay; (3) RT-PCR gene expression analysis of tumor necrosis factor (TNF-α) and tumor suppressor protein (p53); and (4) immunohistochemical analysis of caspase-9 protein expression. The gas chromatography-mass spectrometry results showed that FO had a high content of unsaturated fatty acids including, oleic acid, linolenic acid, and linoleic acid. Oral supplementation with FO (12 mL/kg) resulted in a normal histological appearance without alteration in the DNA integrity and gene expression of TNF-α, p53, and caspase-9 in liver and kidney tissues. As expected, CdCl2 remarkably induced loss of histological integrity, increased DNA comet formation, increased TNF-α and p53 mRNA expression levels and increased the immunoreactivity of caspase-9 expression. When FO was given before administration of CdCl2, these histopathological defects were reversed; necrosis, degeneration, inflammatory cell infiltration, hemorrhage, Kupffer cells, and pyknotic cells were all reduced. These histological improvements induced by FO were accompanied by reduced DNA breakage, downregulated mRNA expression of TNF-α and p53, and downregulated immunohistochemical expression of caspase-9 protein. In conclusion, FO and its constituents may act as signaling molecules and modify the expression of genes involved in proinflammatory cytokine production (TNF-α), cell cycle arrest (p53), and apoptosis (caspase-9), thereby improving biological activities and health.
Databáze: OpenAIRE