The Acute toxicity study of bufadienolides on KM mice (n = 10).

<p>The Acute toxicity study of bufadienolides on KM mice (n = 10).</p

Evaluation of antitumor effects of different Cinobufacin components.

<p>Growth inhibition effects of different concentrations of bufadienolides (Buf), alkaloids (Alk), nucleosides (Nuc), and peptides (Pep) extracted from Cinobufacin on BEL-7402 (A) and BGC-823 cells (B). Cells was monitored for 48hrs after adding different Cinobufacin extracts.</p

IC₅₀ of Cinobufacin components.

<p>IC₅₀ of Cinobufacin components.</p

Effect of bufadienolides on H22 and MFC tumors.

<p>Effect of bufadienolides on H22 and MFC tumors.</p

Tamoxifen-induced recombinase activity of Cre-ER^T2 in the lung tissues of SPC-Cre-ER^T2/TSC1^fx/fx transgenic mice.

<p>DNAs from the lung tissues of SPC-Cre-ER^T2/TSC1^fx/fx transgenic mice treated with vehicle or tamoxifen were examined by PCR to detect <i>TSC1</i> deletion as an indication of Cre-ER^T2 recombinase activity. M, DNA marker; +, a transgenic mouse with <i>TSC1</i> deletion; -, C57BL/6J mouse. Other lanes, offspring from F42 and F67 founders treated with vehicle (vehi) or tamoxifen (tam).</p

Generation of SPC-Cre-ER^T2 mice.

<p>A) Schematic map of SPC-Cre-ER^T2 expression cassette. HSPC-P, human surfactant protein C promoter; Cre-ER^T2, Cre coding sequence fused with a tamoxifen-inducible estrogen receptor. pA, a polyA sequence from SV40 virus. Cre-F primer binding sites, 561–579 bp of Cre-ER^T2 transgene; Cre-R primer binding sites, 976–997 bp of Cre-ER^T2 transgene. The map is drawn in scale. B) Screening SPC-Cre-ER^T2 transgenic mice using PCR. Genomic DNA from each mouse tail was used as template to specifically PCR-amplify the Cre-ER^T2 transgene. M, DNA marker; +, SPC-Cre-ER^T2 plasmid DNA control; -, water control; F8, F13, F16, F42, F67 are five representative founder transgenic mice generated by microinjection of SPC-Cre-ER^T2 expression cassette into fertilized embryos. C) Cre-ER^T2 fusion proteins were detected using Western blot in lung tissues of SPC-Cre-ER^T2 transgenic mice. Lane 1, C57BL/6J mouse; Lane 2, an offspring of F42 founder without Cre-ER^T2 transgene when genotyped using PCR; Lane 3, 4, 5, offspring of F42 founder; Lane 6, 7, 8, offspring of F67 founder. Notice the variable expression levels of Cre-ER^T2 in offspring from the same founder.</p

Tamoxifen-inducible and tissue-specific recombinase activity of Cre-ER^T2 in SPC-Cre-ER^T2/ROSA26R transgenic mice.

<p>A) β-galactosidase activity was detected in the lung alveolar epithelia from a SPC-Cre-ER^T2/ROSA26R transgenic mouse receiving tamoxifen treatment. a & b, lung tissue sections from ROSA26R mice (without Cre-ER^T2 transgene) receiving vehicle (a) or tamoxifen (b); c & d, lung tissue sections from SPC-Cre-ER^T2/ROSA26R transgenic mice receiving vehicle (c) or tamoxifen (d). B) Endogenous β-galactosidase activity was found in lung bronchial epithelia of ROSA26R mouse receiving vehicle (a) and SPC-Cre-ER^T2/ROSA26R transgenic mouse after tamoxifen treatment (b). C) X-gal stained lung tissues of SPC-Cre-ER^T2/ROSA26R transgenic mouse receiving tamoxifen were also immune-stained for proSP-C, an alveolar type II cell-specific marker. Arrows indicate three representative alveolar type II cells co-expressing proSP-C (brown) and β-galactosidase (blue). D) β-galactosidase activity was detected only in the lung alveolar epithelium, but not in other organs from a SPC-Cre-ER^T2/ROSA26R transgenic mouse receiving tamoxifen treatment. a, heart; b, liver; c, kidney; d, intestine; e, lung. All scale bars in this figure equal 100 µm.</p

Omeprazole Alleviates <i>Aristolochia manshuriensis Kom</i>-Induced Acute Nephrotoxicity

<div><p><i>Aristolochia manshuriensis Kom</i> (AMK) is a member of the <i>Aristolochiaceae</i> family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity.</p></div

Omeprazole blocks AA-induced cell injury by upregulating CYP 1A1.

<p>(A) OM induced CYP 1A1 in HKCs. (B) HKCs cells were treated with or without 90 μM OM for 18 h before the addition of 20 μM AA-Na for 48 h. Cell viability was then detected using an MTT assay. **P≤0.01 <i>vs</i>. HKCs; ^## P≤0.01 <i>vs</i>. HKCs after 20 μM AA-Na administration. (C-D) HKCs were stably transfected with PCDNA6-CYP 1A1 (HKC-CYP 1A1) or PCDNA6 (HKC-V; control), and CYP 1A1 was ectopically expressed at the (C) mRNA and (D) protein levels in the targeted cell line. (E) HKC-V and HKC-CYP 1A1 cells were treated with or without 20 μM AA-Na or solvent control for 48 h. Cell viability was detected using an MTT assay. **P≤0.01 <i>vs</i>. HKC-V cells; ^#P≤0.05 <i>vs</i>. HKC-V cells treated with AA-Na. OM, omeprazole; AA-Na, aristolochic acid sodium salt. Data are expressed as mean ± SEM.</p

Omeprazole protects rats against <i>Aristolochia manshuriensis Kom</i>-mediated renal injury.

<p>Alterations in (A) female and (B) male body weight, (C) female and (D) male Kidney weight body weight ratio (KW/BW), (E) female and (F) male serum BUN, and (G) female and (H) male serum CRE in the four rat cohorts. qPCR analysis of (I) female and (J) male renal <i>ngal</i> mRNA levels in the four rat cohorts. Urine Ngal levels of (K) female and (L) males in each cohort. CTL, control; AMK, <i>Aristolochia manshuriensis Kom</i>; OM, omeprazole; O+A, omeprazole and AMK. Data are expressed as mean ± SEM. *P<0.05 <i>vs</i>. CTL cohort; **P<0.01 <i>vs</i>. CTL cohort; ***P<0.001 <i>vs</i>. CTL cohort; ^# P<0.05 <i>vs</i>. AMK cohort; ^## P<0.01 <i>vs</i>. AMK cohort; ^### P<0.001 <i>vs</i>. AMK cohort. n = 6~7.</p