Melatonin in preservation solutions prevents ischemic injury in rat kidneys.

Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The transplantation success depends on the functional preservation of organs prior to transplantation. Currently, the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most commonly used preservation solutions. Despite intensive efforts, the functional preservation of solid organs prior to transplantation is limited to hours. In this study, we modified the UW solution containing components from both the UW and HTK solutions and analyzed their tissue-protective effect against ischemic injury. The composition of the UW solution was changed by reducing hydroxyethyl starch concentration and adding Histidine/Histidine-HCl which is the main component of HTK solution. Additionally, the preservation solutions were supplemented with melatonin and glucosamine. The protective effects of the preservation solutions were assessed by biochemical and microscopical analysis at 2, 10, 24, and 72 h after preserving the rat kidneys with static cold storage. Lactate dehydrogenase (LDH) activity in preservation solutions was measured at 2, 10, 24, and 72. It was not detectable at 2 h of preservation in all groups and 10 h of preservation in modified UW+melatonin (mUW-m) and modified UW+glucosamine (mUW-g) groups. At the 72nd hour, the lowest LDH activity (0.91 IU/g (0.63-1.17)) was measured in the mUW-m group. In comparison to the UW group, histopathological damage score was low in modified UW (mUW), mUW-m, and mUW-g groups at 10, 24, and 72 hours. The mUW-m solution at low temperature was an effective and suitable solution to protect renal tissue for up to 72 h.

Opuntia ficus indica Fruits Ameliorate Cisplatin-Induced Nephrotoxicity in Mice.

This study aims to determine the potential renal protective effects of Opuntia ficus-indica (L.) Miller (OFI) fruits against cisplatin-induced nephrotoxicity in mice. The antioxidant activity of OFI methanol extract was calculated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) free radical scavenging assays. Furthermore, the LC-mass spectroscopy (MS) analysis of the OFI fruit extract was carried out. Mice were treated with OFI extract (250 mg/kg) for 10 d and injected with a single dose of cisplatin (20 mg/kg) on the 7th day. The blood samples were collected to measure blood urea nitrogen (BUN) and serum creatinine level on the 10th day. Their kidneys were removed for histopathological examination. The renal morphological alterations were assessed through the mesangial matrix index and transmission electron microscopy (TEM). The OFI fruit extract showed significant in vitro antioxidant activity. In further, it was revealed that the cisplatin-induced nephrotoxicity in mice was ameliorated; this outcome was supported by both histological examination results and the depicted reduced levels of BUN and serum creatinine. The potent antioxidant compounds which were detected in the extract of OFI fruits such as myricetin, quercetin, luteolin might be responsible for the observed renoprotective effect. The results clarified that the OFI fruit extract could ameliorate cisplatin-induced renal toxicity in mice via including antioxidant and renoprotective compounds.

Protective effect of hyperbaric oxygen treatment on rat intestinal mucosa after mesenteric ischaemia and reperfusion.

INTRODUCTION: Mesenteric ischaemia results from a lack of adequate blood flow to and oxygenation of the mesentery and intestines. The aim of the present study was to evaluate the effect of hyperbaric oxygen treatment (HBOT) on the healing process in intestinal mucosa of rats undergoing mesenteric ischaemia and reperfusion. METHODS: Thirty-two Wistar-Albino rats were divided into four groups of eight: 1) ischaemia/reperfusion (I/R); 2) sham operation; 3) I/R+HBOT started 6 hours after reperfusion; 4) I/R+HBOT started 12 hours after reperfusion. In the I/R groups, a vascular clamp was placed across the superior mesenteric artery to occlude arterial circulation for 60 minutes, followed by reperfusion. A dose of HBOT consisted of 100% oxygen breathing for 90 minutes at 2.5 atmospheres absolute pressure. Thirteen doses of HBOT were administered after ischaemia. The rats were sacrificed on the eighth day, and their intestinal tissues were harvested for histopathologic analysis. The tissue levels of catalase, malondialdehyde, and glutathione were determined. RESULTS: The histopathological scores (HSCORE) were consistent with macroscopic examinations. The scores were significantly higher (worse) in Group 1 compared to Group 2, Group 3, and Group 4 (for all comparisons, P < 0.05). Group 4's HSCORE was significantly higher than those of Group 2 and Group 3 (for both comparisons P < 0.05). Group 3's HSCOREs were only marginally higher than Group 2. Group 3 exhibited higher glutathione levels than Group 1 (P < 0.05). There were no significant differences across the groups with respect to malondialdehyde and catalase levels. CONCLUSION: A beneficial effect of HBOT was observed on oxidative stress and inflammation in acute mesenteric ischaemia-reperfusion.

Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway.

We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl4 group; the CCl4 plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p⟨0.001) in the CCl4 group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p⟨0.001) in fibrotic areas in the CCl4 group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling.

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli.

BACKGROUND: In experimentally induced puromycine aminonucleoside nephrosis (PAN) animal models, nephrotic syndrome with minimal change disease and focal and segmental sclerosis-like nephritis similar to that in human is demonstrated; however, the real mechanism of PAN is not yet elucidated. Platelet derived endothelial cell growth factor (PD-ECGF), an endothelial mitogen protein, is believed to take part in microvessel formation and in stimulation of angiogenesis and its expression has not been totally demonstrated in PAN rats yet. In this study, we aimed to examine PD-ECGF expression in acute and chronic PAN induced in rats and find out the association between its expression and the stages of angiogenesis in kidney. METHODS: For the experiment, twenty-four Male Wistar Albino rats were used and divided into four groups; control group (n = 6), pre-proteinuria group (n = 6), acute group (n = 6) and chronic group (n = 6). We compared statistically all data by One-way ANOVA Test followed by Dunn Multiple Comparison Test. RESULTS: Proteinurea levels in control and pre-proteinuria groups were not statistically different; however, it was remarkably higher in the acute nephrosis group and significantly greater in the chronic nephrosis group than control group (p < 0.0025). In pre-proteinuria group, the serum albumin and creatinine clearances also did not significantly differ from the control group. On the other hand, in the acute and chronic nephrosis groups, serum albumin and creatinine clearances progressively decreased (p < 0.05). In our immunohistochemical studies, we showed elevated PD-ECGF expression in glomeruli of acute and chronic PAN rats. Microscopic and ultrastructural appearances of the glomeruli of acute and chronic PAN showed various sequential steps of angiogenesis, macrophages and immature capillaries with primitive lumens and apoptotic endothelial cells in the increased mesangial matrix. CONCLUSIONS: It is reported that acute and chronic PAN progressively increase PD-ECGF expression and following induction of angiogenesis in the affected glomeruli.