Altered cisplatin pharmacokinetics during nonalcoholic steatohepatitis contributes to reduced nephrotoxicity

Disease-mediated alterations to drug disposition constitute a significant source of adverse drug reactions. Cisplatin (CDDP) elicits nephrotoxicity due to exposure in proximal tubule cells during renal secretion. Alterations to renal drug transporter expression have been discovered during nonalcoholic steatohepatitis (NASH), however, associated changes to substrate toxicity is unknown. To test this, a methionine- and choline-deficient diet-induced rat model was used to evaluate NASH-associated changes to CDDP pharmacokinetics, transporter expression, and toxicity. NASH rats administered CDDP (6 mg/kg, i.p.) displayed 20% less nephrotoxicity than healthy rats. Likewise, CDDP renal clearance decreased in NASH rats from 7.39 to 3.83 mL/min, renal secretion decreased from 6.23 to 2.80 mL/min, and renal CDDP accumulation decreased by 15%, relative to healthy rats. Renal copper transporter-1 expression decreased, and organic cation transporter-2 and ATPase copper transporting protein-7b increased slightly, reducing CDDP secretion. Hepatic CDDP accumulation increased 250% in NASH rats relative to healthy rats. Hepatic organic cation transporter-1 induction and multidrug and toxin extrusion protein-1 and multidrug resistance-associated protein-4 reduction may contribute to hepatic CDDP sequestration in NASH rats, although no drug-related toxicity was observed. These data provide a link between NASH-induced hepatic and renal transporter expression changes and CDDP renal clearance, which may alter nephrotoxicity.

Simultaneous Determination of Ornidazole and Dexamethasone Sodium Phosphate in Compound Ornidazole Film by HPLC / 中国药房

OBJECTIVE:To establish a method for the simultaneous determination of ornidazole and dexamethasone sodium phosphate in Compound ornidazole film. METHODS:HPLC was performed on the column of Inertsil ODS-3 with mobile phase of methanol-20 mmol/L phosphate buffer(pH was adjusted to 7.40 with glacial acetic acid)(55∶45,V/V)at a flow rate of 1.0 ml/min, column temperature was 30 ℃,detection wavelength was 242 nm and volume injection was 10 μl. RESULTS:The linear range were 1-100μg/ml for both ornidazole(r=0.999 7)and dexamethasone sodium phosphate(r=0.999 9);RSDs of precision,stabili-ty and reproducibility tests were lower than 2.0%;recoveries were 96.50%-99.80%(RSD=1.02%,n=9) and 96.50%-99.60%(RSD=0.99%,n=9). CONCLUSIONS:The method is specific with good precision and stability and high accuracy,and can be used for the simultaneous determination of ornidazole and dexamethasone sodium phosphate in Compound ornidazole film.

Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1

The differentiation of periodontal ligament (PDL) progenitor cells is important for maintaining the homeostasis of PDL tissue and alveolar bone. Vitamin C (VC), a water-soluble nutrient that cannot be biosynthesized by humans, is vital for mesenchymal stem cells differentiation and plays an important role in bone remodeling. Therefore, the objective of this study was to determine the function and mechanism of VC in PDL progenitor cells osteogenic differentiation at the molecular level. We demonstrated that VC could induce the osteogenic differentiation and maturation of PDL progenitor cell without other osteogenic agents. During the process, VC preferentially activated ERK1/2 but did not affect JNK or p38. Co-treatment with ERK inhibitor effectively decreased the Vitamin C-induced expression of Runx2. ERK inhibitor also abrogated Vitamin C-induced the minimized nodules formation. PELP1, a nuclear receptor co-regulator, was up-regulated under VC treatment. PELP1 knockdown inhibited ERK phosphorylation. The overexpression of PELP1 had a positive relationship with Runx2 expression. Taken together, we could make a conclude that VC induces the osteogenic differentiation of PDL progenitor cells via PELP1-ERK axis. Our finding implies that VC may have a potential in the regeneration medicine and application to periodontitis treatment.

cDNA cloning and sequencing of MH2 domain of Smad1 from human dental papilla cells / 实用口腔医学杂志

Objective:To clone and sequence cDNA of MH2 domain of Smad1 gene from human dental papilla cells. Methods:Total RNA was isolated from primarily cultured human dental papilla cells and reversely transcribed into single stranded cDNA.The desired DNA product was obtained by PCR with two gene specific primers.The segment was inserted into PUC19 vector and the plasmid was transformed into E.coli JM109.The double stranded cDNA of positive clone was sequenced.Results:The sequence of MHz domain of Smad1 cloned from human dental papilla cells was consistent with that reported by Hoodless et al. Conclusion:Smad1 exists in human dental papilla cells,BMP signaling may be mediated by smad1 in human dental papilla cells.

Transforming growth factor ?1 induces apoptosis in mouse odontoblast cell line MDPC-23 / 实用口腔医学杂志

Objective:To investigate if transforming growth factor-?1 (TGF-?1) induces apoptosis in odontoblast cell line MDPC-23. Methods:MDPC-23 cells were treated with TGF-?1 at 0.5,2.5 or 10 ng/ml for 48 h,apoptosis of MDPC-23 cells was detected by annexin V and propidium iodide (PI) staining, cell death detection ELISA and DNA electrophoretic analysis. Results: Consistent results were obtained from three different methods.TGF-?1 at 0.5-10 ng/ml induced apoptosis of MDPC-23 cells in a dose-dependent manner. Conclusion:TGF-?1 may paly a role in apoptosis of odontoblasts.