Dietary D-glucarate effects on the biomarkers of inflammation during early post-initiation stages of benzo[a]pyrene-induced lung tumorigenesis in A/J mice

Abstract

Abstract. Previous studies showed that dietary calcium D-glucarate (CG) inhibited benzo[a]pyrene (B[a]P)-inducedA/J mouse lung tumorigenesis, suppressing cell proliferation and chronic inflammation and inducing apoptosis during late post-initiation stages. The present study aimed to investigate changes in the homeostasis of cytokines in blood serum, as well as alterations in biomarkers of inflammation and apoptosis in lung tissue caused by dietary CG during early post-initiation stages of B[a]P-induced lung tumorigenesis. Two doses of 3 mg of B[a]P were given intragastrically to A/J mice 2 weeks apart. CG administration in the AIN-93G diet (2 and 4%, w/w) commenced at 2 weeks following the second dose of B[a]P. The levels of interleukin (IL)-6, IL-10 and tumor necrosis factor α (TNFα) in blood serum were investigated by FCAP array analysis. Two weeks after the second dose of B[a]P, approximately 8-and 28-fold increases of TNFα and IL-6, respectively, occurred in the blood serum and an approximately 16% decrease of IL-10 levels compared to the untreated control group was noted. At 4 weeks after the second dose of B[a]P and after 2 weeks of CG administration in the diet, the 2 and 4% CG diets significantly reduced the levels of IL-6 and TNFα (by 70 and 33%, respectively). In a dose-related manner, the diets also increased the level of antiinflammatory cytokine IL-10 compared to the B[a]P group. At 6 weeks after the second dose of B[a]P, the cytokine levels in the serum continued to show a decrease in the CG-treated groups. These events are accompanied by an increased level of cleaved caspase-9 product with a molecular weight of 37 kDa. In conclusion, dietary D-glucarate decreases the level of proinflammatory cytokines, increases the level of the anti-inflammatory cytokine IL-10 during early post-initiation stages of B[a]P-induced lung tumorigenesis in A/J mice and affects apoptotic induction.

Novel colon‐available triterpenoids identified in raspberry fruits exhibit antigenotoxic activities in vitro

“…The presence of p ‐coumaroyl glucarate derivatives in raspberries, and their survival in ileal fluids, could be of significance as D‐glucaric acid has long been known to have anticancer effects in carcinogen‐induced animal models . Although originally thought to act through inhibition of β‐glucuronidase and increased detoxification of carcinogens, it may have more complex effects via anti‐inflammatory systems and apoptotic events . As these coumaroyl glucarate esters survive into the ileal fluid, they could deliver potentially bioactive glucaric acid throughout the GI tract, ultimately to the colon, where it could have a role in chemoprevention of cancer.…”

Disruption of Renal Tubular Mitochondrial Quality Control by Myo-Inositol Oxygenase in Diabetic Kidney Disease

“…Daily supplementation of D-glucarate has some key beneficial effects (i.e., detoxification of noxious substances and anticancer regimens). [41][42][43] The primary mechanisms of action of D-glucarate may be through its ability to enhance detoxification of toxins and carcinogens as well as its antioxidative potential, 44,45 which may be linked to the inhibition of MIOX. In addition, a derivative of D-glucaric acid, D-saccharic acid 1, 4-lactone, has been recently reported to be protective in both diabetes and its renovascular complications in rats.…”

“…D-glucarate (1% or 2% [wt/wt]) was mixed with dietary chow. 42 A diabetic state was induced by daily intraperitoneal injection of STZ (50 mg/kg body wt; Sigma-Aldrich) for 5 days. One week after the injection, mice with blood glucose levels.250 mg/dl were selected Figure 10.…”

A review on plastic bioaccumulation, potential health effects and the potential to enhance biotransformation using herbal medicine and nutritional supplements

“…Caclium D-Glucarate (CDG) inhibits β-glucuronidase, therefore enhances glucuronidation conjugation. 87 CDG is in cruciferous vegetables or vegetables from the Brassicaceae family.…”