Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: Two birds with one stone.

Deposition of calcium oxalate (CaOx) crystals and oxidative stress-induced injury of renal tubular epithelial cell are the primary pathogenic factors of nephrolithiasis. In this study we investigated the beneficial effects of metformin hydrochloride (MH) against nephrolithiasis and explored the underlying molecular mechanism. Our results demonstrated that MH inhibited the formation of CaOx crystals and promoted the transformation of thermodynamically stable CaOx monohydrate (COM) to more unstable CaOx dihydrate (COD). MH treatment effectively ameliorated oxalate-induced oxidative injury and mitochondrial damage in renal tubular cells and reduced CaOx crystal deposition in rat kidneys. MH also attenuated oxidative stress by lowering MDA level and enhancing SOD activity in HK-2 and NRK-52E cells and in a rat model of nephrolithiasis. In both HK-2 and NRK-52E cells, COM exposure significantlylowered the expressions of HO-1 and Nrf2, which was rescued by MH treatment even in the presence of Nrf2 and HO-1 inhibitors. In rats with nephrolithiasis, MH treatment significantly rescued the down-regulation of the mRNA and protein expression of Nrf2 and HO-1 in the kidneys. These results demonstrate that MH can alleviate CaOx crystal deposition and kidney tissue injury in rats with nephrolithiasis by suppressing oxidative stress and activating the Nrf2/HO-1 signaling pathway, suggesting the potential value of MH in the treatment of nephrolithiasis.

An Assessment of Engineered Calcium Oxalate Crystal Formation on Plant Growth and Development as a Step toward Evaluating Its Use to Enhance Plant Defense.

The establishment of new approaches to control chewing insects has been sought not only for direct use in reducing crop loss but also in managing resistance to the pesticides already in use. Engineered formation of calcium oxalate crystals is a potential strategy that could be developed to fulfill both these needs. As a step toward this development, this study investigates the effects of transforming a non-calcium oxalate crystal accumulating plant, Arabidopsis thaliana, into a crystal accumulating plant. Calcium oxalate crystal accumulating A. thaliana lines were generated by ectopic expression of a single bacterial gene encoding an oxalic acid biosynthetic enzyme. Biochemical and cellular studies suggested that the engineered A. thaliana lines formed crystals of calcium oxalate in a manner similar to naturally occurring crystal accumulating plants. The amount of calcium oxalate accumulated in leaves also reached levels similar to those measured in the leaves of Medicago truncatula in which the crystals are known to play a defensive role. Visual inspection of the different engineered lines, however, suggested a phenotypic consequence on plant growth and development with higher calcium oxalate concentrations. The restoration of a near wild-type plant phenotype through an enzymatic reduction of tissue oxalate supported this observation. Overall, this study is a first to provide initial insight into the potential consequences of engineering calcium oxalate crystal formation in non-crystal accumulating plants.

Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study.

To investigate that lemon juice could be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia, 30 patients with hypocitraturic urinary calcium stones were enrolled into study. The patients were divided into three groups equally. Exactly 60 mEq/day fresh lemon juice ( approximately 85 cc/day) and potassium citrate (60 mEq/day) were given to the patients of first and second group, respectively. Dietary recommendations were made for the third group. Blood and 24-h urine tests were performed before treatment and repeated 3 months later. The differences between demographic datas of groups were not significant. There was no significant difference between values of blood tests performed before and after treatment in all groups. Statistically significant differences were found between pre- and post-treatment urine values in each group. Although there was no significant difference between pre-treatment citrate levels of the groups. A significant difference was found between post-treatment citrate levels of the groups. There was 2.5-, 3.5- and 0.8-fold increase in urinary citrate level of lemon juice, potassium citrate and dietary recommendation groups, respectively. Urinary calcium level was decreased only in lemon juice and potassium citrate groups after treatment. While there was no significant difference between pre- and post-treatment urinary oxalate levels in all groups, a significant decrease in urinary uric acid levels was determined in all groups. We suggest that lemon juice can be an alternative in the treatment of urinary calcium stones in patients with hypocitraturia. Additionally, dietary recommendations can increase effectiveness of the treatment.

Independent assessment of the growth and aggregation of calcium oxalate crystals using the Coulter counter.

The growth and aggregation of calcium oxalate seed crystals in a metastable solution of this salt were assessed separately by using the Coulter counter to measure the net increase in total crystal volume and the percentage change in total crystal number respectively. The value of assessing crystal growth and aggregation in these terms was shown by using these parameters to measure the inhibitory effect of a normal human urine. Independent assessment of growth and aggregation enabled a more accurate interpretation of experimental events than was possible by considering the two processes in combination. The method therefore has the potential of improving the discrimination between the inhibitory activities of different urines.