Search

Aims: Transient receptor potential (TRP) channels are non-selective cation channels that promote influx of Ca2+, Mg2+ and monovalent cations into cells. TRP channel subfamily C, member 6 (TRPC6) is widely expressed - next to several other tissues - in the kidney, and gene variations were linked to fibrosing renal disease. Here we aimed to investigate the putative role of TRPC6 channels in acute kidney injury (AKI). Since ischemia/reperfusion injury is known relate to Ca2+ overload, we hypothesized that inhibition of TRPC6 ameliorates AKI. Methods: We used Trpc6-/- mice and SH045, a pharmacological inhibitor of TRPC6, to evaluate short-term AKI outcomes. Ischemia was induced after right–sided nephrectomy by clipping the renal pedicle of the left kidney for 20 or 17.5 minutes. SH045 was used for intravenous injection (2 mg/kg) 30 minutes before I/R surgery in the pharmacological studies with WT mice. Results: Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influence the short-term outcomes of AKI. Blood markers (Creatinine in WT [131.4±33.3 µmol/l] vs Trpc6-/- [159.6±41.7 µmol/l] mice after 24 hours of reperfusion and in the pharmacological study: 17.5 min-I/R vehicle [199.5±21.8 µmol/l] versus 17.5 min-I/R SH045 [172.6±31.6 µmol/l], and 20 min-I/R vehicle [212.2±8.4 µmol/l] versus 20 min-I/R SH045 [226.2±28.6 µmol/l], all comparisons are n.s.), renal expression of epithelial damage markers, tubular injury and renal inflammatory response assessed by histological analysis were similar in wild-type mice compared to Trpc6-/- mice as well as in vehicle-treated versus SH045-treated mice. In addition, our results also found no effect of TRPC6 modulation on renal myogenic tone by using SH045 to perfuse isolated kidneys. Conclusion: Therefore, we conclude that TRPC6 does not play role on the acute phase of AKI. Further studies should focus if TRPC6 inhibition could be protective in terms of long-term outcome of an AKI.

A linear relationship between the standard enthalpy of formation from binary oxides, ΔfH°ox, and the Goldschmidt tolerance factor, t, for some AIIBIVO3 (A = Ca, Sr, Ba; B = Ti, Zr, Hf, Ce, Pr, Tb, U, Pu, Am) perovskite oxides was used for estimation of ΔfH°ox of Pr-substituted barium zirconates BaZr1–xPrxO3. A dependence of the relative change of the standard entropies, S°298, on the relative change of the molar volumes in the reactions of formation of AIIBIVO3 (A = Ca, Sr, Ba; B = Ti, Zr, Hf, Ce) from binary oxides was also found to be linear. Using this dependence, a relatively precise method of estimating S°298 was proposed, and S°298 of BaPrO3 was calculated as (162.8 ± 2.8) J·mol–1·K–1. Knowing S°298 of BaPrO3 and using the literature data for S°298 of BaZrO3, the values of S°298 of BaZr1–xPrxO3 were predicted on the assumption that BaZr1–xPrxO3 is a regular or ideal solution of BaPrO3 in BaZrO3 as evidenced by the very small enthalpy of mixing calculated based on the estimated ΔfH°ox. The values of standard entropy changes, ΔfS°ox, and Gibbs energy changes, ΔfG°ox, for the reactions of formation of BaZr1–xPrxO3 from BaO, ZrO2 and PrO2 were also estimated. Substituting Pr for Zr in BaZr1–xPrxO3 results in ΔfH°ox and ΔfG°ox becoming more positive, indicating the decrease of the relative stability with respect to the corresponding binary oxides. Expanded uncertainties of the estimated values of ΔfH°ox and ΔfG°ox are equal to 14 kJ · mol–1, and those of S°298 and ΔfS°ox — less than 2.8 J · mol–1·K–1 and 3.5 J · mol–1·K–1, respectively, for BaZr1–xPrxO3 (x = 0.0–1.0).

Crystal structure of mono-β-alaninium chloride has been studied by single crystal X-ray diffraction. The compound crystallizes in the orthorhombic system. The space group is Pbca, with the following lattice constants: a = 9.7414(5) Å, b = 7.4671(6) Å, c = 16.5288(11) Å, V = 1202.31(14) Å3, Z = 8. The asymmetric unit contains one β-alaninium cation (+NH3CH2CH2COOH) and one chloride anion. The structure was shown to consist of layers stacked along the c-axis and connected with each other by weak van der Waals forces. Each layer consists of two halves linked by hydrogen bonds between carbonyl and NH3 + groups and, also, between NH3 + groups and Cl– anions. Fourier transform infrared spectrum of β-alaninium chloride was recorded and analyzed. The spectroscopic results were found to support the conclusions of the structural study.