Fig 1: Radioprotective capability of atorvastatin in the intestinal epithelium. (a) RT resulted in apoptosis, ROS-induced oxidative stress (DNA damage and inflammation), and the impairment of intestinal epithelium (fibrosis and impaired intestinal barrier integrity) in our murine model. (b) The expression level of autophagy-associated molecules might determine the integrity of the intestinal tissue after RT. Atorvastatin administration activates the biological functions of autophagy, including attenuating apoptosis, DNA damage, oxidative stress, inflammation, and fibrosis, and thus decreases the injury score of the intestinal epithelium. Additionally, atorvastatin administration stimulates the production of antioxidants molecules, such as HO-1 and Trx. Therefore, atorvastatin may effectively help escalate RT dose to increase tumor control in patients receiving abdominal and pelvic RT by reducing RT-associated enteritis.
Fig 2: Attenuation of anti-DENV activity of lucidone by inhibition of HO-1 expression and activity. (A, B) Silencing HO-1 expression attenuated the antiviral activity of lucidone. DENV-infected Huh-7 cells were transfected with different amounts of HO-1-specific shRNA (0.25–2 μg) or nonspecific shRNA, and then treated with or without lucidone (40 μM) for 3 days. (C, D) HO-1 inhibitor attenuated the antiviral activity of lucidone. DENV—infected Huh-7 cells were treated with different concentrations of SnPP (0–20 μM) with or without lucidone (40 μM) for 3 days. Protein synthesis and RNA replication were analyzed by western blotting and qRT-PCR, respectively. Western blotting was performed using anti-DENV NS2B antibody, anti-HO-1, and anti-GAPDH antibody. GAPDH protein levels showed equal loading of cell lysates. Total cellular RNA was extracted and analyzed by qRT-PCR. The DENV RNA level was normalized by cellular gapdh mRNA. “0” indicates treatment with 0.1% DMSO. DENV RNA levels were presented as percentage changes compared to those in parental Huh-7 cells, in which the level was presented as 1. Results are expressed as mean ± SD (error bar) of three independent experiments. *P versus non-SnPP treated or non-specific shRNA transfected control group; #P versus lucidone alone treated control group.
Fig 3: Protein levels in isolated rat hearts at T3. (A) Changes in relative expression levels of Nrf2, NQO1, HO-1 and SOD1. (B) Western blotting was performed to evaluate the protein expression levels of Nrf2, HO-1, NQO1 and SOD1. The IR group exhibited the lowest protein expression levels of Nrf2, HO-1, NQO1 and SOD1. The P50 group exhibited the highest protein expression levels. aP<0.05 vs. N. bP<0.05 vs. IR. cP<0.05 vs. P50. Data are presented as the mean ± SD (n=3). T3, end of reperfusion; Nrf2, nuclear factor-E2 related factor 2; HO-1, heme oxygenase 1; NQO1, NADH-quinone oxidoreductase-1; SOD1, superoxide dismutase 1; IR, ischemia-reperfusion; P10, 10 µmol/l pinacidil; P30, 30 µmol/l pinacidil; P50, 50 µmol/l pinacidil; N, normal.
Fig 4: Gene expression levels in isolated rat hearts at T3. Nrf2 pathway-associated mRNA expression levels were lowest in the IR group. The P50 group exhibited the highest mRNA expression levels. aP<0.05 vs. N. bP<0.05 vs. IR. cP<0.05 vs. P50. Data are presented as the mean ± SD (n=3) and were analyzed by one-way ANOVA followed by Bonferroni's correction. T3, end of reperfusion; Nrf2, nuclear factor-E2 related factor 2; IR, ischemia-reperfusion; P10, 10 µmol/l pinacidil; P30, 30 µmol/l pinacidil; P50, 50 µmol/l pinacidil; N, normal; HO-1, heme oxygenase 1; NQO1, NADH-quinone oxidoreductase-1; SOD1, superoxide dismutase 1.
Fig 5: Atorvastatin reduces RT-induced ROS levels by increasing the expression of antioxidants. (a) IHC analysis of the 4-HNE expression in jejunum tissue sections from five groups. Scale bar = 100 μm. (b) The expression level of 4-HNE was determined by western blot analysis. The relative amount of 4-HNE was quantified as the 4-HNE to GAPDH ratio. The relative ratios of the five groups are represented in the bar graph (the control group is arbitrarily presented as 1). The data are expressed as mean ± SE of three independent experiments. ∗P < 0.05; ∗∗P < 0.01. (c) IHC analysis of the expression of HO-1, Trx1, and Gpx4 in jejunum tissue sections from five groups. Scale bar = 100 μm. (d) The expression levels of HO-1, Trx1, and Gpx4 were determined by western blot analysis. The relative amounts were quantified as the HO-1, Trx1, or Gpx4 to actin or GAPDH ratios and are represented in the bar graph. The data are expressed as mean ± SE of three independent experiments. The relative ratio of the control group is arbitrarily presented as 1. ∗P < 0.05; ∗∗P < 0.01. (e) TrxR activity of five groups was measured and is represented as mU/mg protein. The data are expressed as mean ± SE of three independent experiments. ∗P < 0.05; ∗∗P < 0.01.
Supplier Page from Abcam for Anti-Heme Oxygenase 1 antibody