Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 (HIF1) and associated proteins. Dapagliflozin improved renal function. Dapagliflozin reduced renal expression of Bax, renal tubule injury and TUNEL-positive cells and increased renal expression of HIF1 in IR-injured mice. HIF1 inhibition by albendazole negated the renoprotective effects of dapagliflozin treatment in IR-injured mice. In vitro, dapagliflozin increased the expression of HIF1, AMP-activated protein kinase (AMPK), and ERK and increased cell survival of hypoxic HK2 cells in a dose-dependent manner. In conclusion, dapagliflozin attenuates renal IR injury. HIF1 induction by dapagliflozin may play a role in renoprotection against renal IR injury.

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Neutral pH and low-GDP PDF likely produce fewer changes in markers of endothelial dysfunction compared to conventional PDF in incident PD patients.

Although titanium-based implants are widely used in orthopedic and dental clinics, improved osseointegration at the bone–implant interface is still required.

Aliskiren has anti-inflammatory and antifibrotic effects in an experimental unilateral ureteral obstruction mouse model.

These studies were performed to determine if changes in luminal sodium chloride concentration ([NaCl]) might alter macula densa intracellular pH. Isolated thick ascending limbs with attached glomeruli were bathed in a 150 mM NaCl Ringer's solution and perfused in vitro with a 25 mM NaCl solution; N-methyl-D-glucamine cyclamate was used to substitute for NaCl. Macula densa cells were loaded with BCECF and intracellular pH was monitored using a microscope based-dual excitation photometer system. Control intracellular pH for all experiments in which tubules were initially perfused with 25 mM NaCl averaged 7.22 +/- 0.06; N = 28. Increasing luminal [NaCl] from 25 to 150 mM elevated macula densa pH by 0.15 +/- 0.03 (N = 6; P < 0.05) while increasing just luminal [Na] from 25 to 150 mM alkalinized macula densa cells by 0.17 +/- 0.05 (N = 6; P < 0.05). In addition, there was a highly significant linear relationship between luminal [Na] and intracellular pH between 25 and 150 mM NaCl. Other studies were performed to assess the effects of amiloride, an inhibitor of Na:H exchange, on macula densa intracellular pH. Addition of amiloride, to the 25 mM NaCl perfusate acidified macula densa cells by 0.09 +/- 0.03 (N = 6; P < 0.001) and significantly attenuated the increase in pH obtained when luminal [NaCl] was raised from 25 to 150 mM. Other studies evaluated the effects of inhibition of Na:2Cl:K cotransport on macula densa pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin exerts renoprotective effects in an experimental unilateral ureteral obstruction rat model via anti-apoptotic and anti-inflammatory actions.

Although cisplatin is a highly effective antineoplastic agent, nephrotoxicity is its major clinical problem. Recently, it was reported that Spirulina, a blue-green algae, has potent antioxidant properties. The aim of this study was to establish the possible protective role of C-phycocyanin (PC), one of the active ingredients of Spirulina, against cisplatin-induced nephrotoxicity. This study was carried out using human kidney-2 (HK-2) cells and male C57BL6 mice. Cells and mice were divided into four groups; untreated control group, PC-treated control group, cisplatin-treated group, and PC plus cisplatin-treated group. The molecular, functional, and structural parameters were measured. PC significantly attenuated blood urea nitrogen, serum creatinine, renal histological damages, and apoptotic cell death in cisplatin-treated mice. The cisplatin-induced cell death was significantly attenuated in cells pretreated with PC. PC also significantly attenuated the elevation of p-ERK, p-JNK, and p-p38 induced by cisplatin treatment. The expression of Bax, caspase-9, and caspase-3 in cisplatin-treated cells were also decreased by PC treatment. In conclusion, PC ameliorates cisplatin-induced nephrotoxicity and, at least in part, suppression of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 may be involved in this mechanism.