Secoisolariciresinol diglucoside mitigates benzo[a]pyrene-induced liver and kidney toxicity in mice via miR-101a/MKP-1-mediated p38 and ERK pathway. (January 2022)

• Record Type: Journal Article
• Authors: Ge, Junlin; Hao, Rili; Rong, Xue; Dou, Q. Ping; Tan, Xintong; Li, Guannan; Li, Feng; Li, Dapeng
• Is Part Of: Food and chemical toxicology. Volume 159(2022)
• Publication Date: 2022-01
• Subjects: Benzo[a]pyrene -- Secoisolariciresinol diglucoside -- Hepatotoxicity -- Nephrotoxicity -- miR-101a -- MAPK pathway; BaP Benzo[a]pyrene -- MAPK Mitogen-activated protein kinase -- miR-101 microRNA 101a -- MKP-1 protein-mitogen-activated protein kinase phosphatase 1 -- SDG Secoisolariciresinol diglucoside; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2021.112733
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Benzo[a]pyrene (BaP) can cause hepatorenal toxicity. Secoisolariciresinol diglucoside (SDG), a polyphenolic compound present in flaxseed, has shown a variety of biological activities including antioxidant, anti-inflammatory, anti-apoptotic effects. This study aimed to investigate the protective effects and working mechanisms of SDG against BaP-induced hepatorenal injury. Forty male mice were administrated daily (via gastric gavage; 4 weeks) with 0.9% saline (control), BaP (75 mg/kg body weight (b.w.)), SDG (100 mg/kg b.w.), SDG (100 mg/kg b.w.)+BaP (75 mg/kg b.w.). Results showed that the mice treated with SDG + BaP had significantly (P < 0.05) higher body weight, lower organ-to-body weight ratio, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) activities, and less levels of serum creatinine (CRE) and blood urea nitrogen (BUN) than those treated with BaP alone. SDG administration alleviated BaP-induced oxidative damages, inflammation and apoptosis. Furthermore, it significantly (P < 0.05) downregulated phosphor-p38 (p-p38) and phosphor-extracellular regulated protein kinases (p-ERK) levels, upregulated mitogen-activated protein kinase phosphatase-1 (MKP-1) level, and suppressed miR-101a expression compared with BaP alone group. Taken together, these results showed for the first time that SDG has protective effects against BaP-induced liver and kidney toxicity in mice through regulating oxidative stress, inflammation and apoptosis via miR-101a/MKP-1-mediated p38 and ERK pathway. Graphical abstract: Image 1 Highlights: BαP causes liver and kidney damage via inducing inflammation and apoptosis in mice. BαP exposure increases the levels of miR-101a and decreases the level of MKP-1. SDG mitigates BαP-induced liver and kidney injury via MAPK pathway. MiR-101a as a critical regulator of MKP-1 involves in the SDG's protective effect.