secoisolariciresinol-diglucoside and Chemical-and-Drug-Induced-Liver-Injury

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.

Topics: Acute Kidney Injury; Animals; Benzo(a)pyrene; Butylene Glycols; Chemical and Drug Induced Liver Injury; Dual Specificity Phosphatase 1; Glucosides; Male; MAP Kinase Signaling System; Mice; MicroRNAs; Protective Agents

The present study was designed to evaluate the in vitro and in vivo ameliorative antioxidant potential of secoisolariciresinol diglucoside (SDG). In vitro antioxidant activity of synthetic SDG was carried out using DPPH, reducing power potency, and DNA protection assays. Wistar albino rats weighing 180-220 g were used for in vivo studies and liver damage was induced in the experimental animals by a single intraperitoneal (I.P.) injection of CCl(4) (2 g/kg b.w.). Intoxicated animals were treated orally with synthetic SDG at (12.5 and 25 mg/kg b.w.) and Silymarin (25 mg/kg) for 14 consecutive days. The levels of catalase (CAT), superoxide dismutase (SOD), peroxidase (POX), and lipid peroxidase (LPO) were measured in liver and kidney homogenates. The synthetic SDG exerts high in vitro antioxidant potency as it could scavenge DPPH at a IC(50) value of 78.9 μg/ml and has dose-dependent reducing power potency and protected DNA at 0.5 mg/ml concentration. Oral administration of synthetic SDG at 12.5 and 25 mg/kg b.w. showed significant protection compared to Silymarin (25 mg/kg) and the activities of CAT, SOD, and POX were markedly increased (P < 0.05), whereas LPO significantly decreased (P < 0.001) in a dose-dependent manner in liver and kidney in both pre- and post-treatment groups when compared to toxin-treated group. The results of in vitro and in vivo investigations revealed that synthetic SDG at 25 mg/kg b.w. is associated with beneficial changes in hepatic enzyme activities and thereby plays a key role in the prevention of oxidative damage in immunologic system.

Topics: Animals; Biphenyl Compounds; Butylene Glycols; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Free Radical Scavengers; Free Radicals; Glucosides; Kidney; Lipid Peroxidation; Liver; Malondialdehyde; Oxidation-Reduction; Peroxidase; Picrates; Rats; Rats, Wistar; Superoxide Dismutase