The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na and Ca . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.

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Renal ischemia/reperfusion (I/R) injury resulting in acute renal failure, is a major clinical problem due to its high mortality rate. Renal I/R increases the reactive oxygen species, secretion of inflammatory cytokines, chemokines and other factors. This suggests that initiating the apoptosis process in the presence of oxidative stress may play a role in life‐threatening conditions, such as ischemia. Ischemia reperfusion‐induced renal damage can result in renal failure and death. Although many treatment procedures have been carried out to reduce or destroy renal I/R damage in experimental models, so far, a routine method of treatment has not yet been found. For this reason, the current study was planned to investigate the possible protective effects of evodiamine on tissue damage caused by ischemia‐reperfusion in kidney tissue in rats and an experimental renal I/R model was used for this purpose. Four groups were formed in the study: the control, sham control, ischemia reperfusion (I/R), and evodiamine (10 mg/kg) + I/R groups. The effects of evodiamine against kidney I/R injury were investigated. TAS (total oxidant status), TOS (total oxidant status), interleukin‐1β (IL‐1β), IL‐6, IL‐10 and tumor necrosis factor‐α levels were determined by enzyme‐linked immunosorbent assay. The oxidative stress index was calculated from TAS and TOS levels. In addition, the renal ischemia reperfusion injury was examined histopathologically. The IL‐10 and TAS levels in the I/R group decreased when compared with the control and Sham groups, while these levels increased in the evodiamine group. Histopathologic examination revealed that caspase 3 and nuclear factor‐κB levels decreased in the evodiamine group compared with the I/R group. The application of evodiamine significantly reduced ischemia reperfusion‐induced kidney damage due to its antioxidant, anti‐inflammatory and antiapoptotic properties.

Objective:High altitude and hypoxic preconditioning have cardioprotective effects by increasing coronary vascularity, reducing post-ischemic injury, and improving cardiac function. Our purpose was to examine if intermittent hypoxia treatment has any restoring effects related to the possible role of the HIF-1/VEGF pathway on diabetic cardiomyopathy.Methods:Wistar Albino male rats (n=34) were divided into four groups: control (C), intermittent hypoxia (IH), diabetes mellitus (DM), and diabetes mellitus plus intermittent hypoxia (DM+IH). Following a streptozotocin (STZ) injection (50 mg/kg, i.p.), blood glucose levels of 250 mg/dL and above were considered as DM. IH and DM+IH groups were exposed to hypoxia 6 h/day for 42 days at a pressure corresponding to 3000 m altitude. Twenty-four hours after the IH protocol, hearts were excised. Hematoxylin and eosin-stained apical parts of the left ventricles were evaluated. Hypoxia inducible factor-1 (HIF-1), vascular endothelial growth factor 164 (VEGF164), and VEGF188 polymerase chain reaction products were run in agarose gel electrophoresis. Band density analysis of UV camera images was performed using Image J. The data were compared by one-way ANOVA, repeated measures two-way ANOVA, and the Kruskal-Wallis test.Results:The percent weight change was lower in the DM group than in the controls (p=0.004). The tissue injury was the highest in the DM group and the least in the IH group. Diabetes decreased, whereas the IH treatment increased the vascularity. A decrease was observed in the VEGF188 mRNA levels in the DM+IH group compared with the C group, but there were no difference in HIF-1α and VEGF164 mRNA levels between the groups.Conclusion:The IH treatment restored the diabetic effects on the heart by reducing tissue injury and increasing the capillarity without transcriptional changes in HIF-1/VEGF correspondingly.

In this study, we evaluated the anti-oxidant and anti-inflammatory effect of caftaric acid against ulcer produced by indomethacin in gastric mucosa. Female Sprague Dawley albino rats were divided into five groups: control (saline group, n = 8), negative control (indomethacin group, n = 8), positive control (omeprazole group, n = 8), low dose therapy (caftaric acid, n = 8), and high dose therapy (caftaric acid, n = 8). At the end of the experiment, all rats were sacrificed and gastric mucosa samples were removed for macroscopic and biochemical analysis. In our study, we detected that oxidant parameter values and cytokine levels increased in the negative control group, but total antioxidant status reduced, whereas, cytokine and oxidant parameter levels were significantly reduced due to low and high doses of caftaric acid administration. But another important point to note is that high dose caftaric acid therapy performed gastroprotective effect as omeprazole. In the macroscopic evaluation, there were reductions in ulcer sizes with a low and high dose of caftaric acid administration in contrast to the negative control group. As a result of our study, caftaric acid showed anti-oxidant and anti-inflammatory effects in indomethacin-induced gastric ulcer in rats.