Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3... more Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3 could be activated also by oxidative stress make Puromycin Aminonucleoside (PAN) Nephrosis model very appropriate for examination of STAT3 expression changes in glomerular pathology. Along with a control group, three PAN groups sacrificed on different days were formed by the i.p. injection of PAN for 5 consecutive days. Throughout the experiment, 24-hour-urines were collected on specific days and proteinuria levels were monitored. At the end of the experiments, tissue specimens were stained immunohistochemically for both total and phosphorylated STAT3 and evaluated subjectively. They were also examined ultrastructurally in transmission electron microscope. The proteinuria levels did not increase significantly on 5th day but showed a dramatic increase on 10th and 15th days. On 20th and 25th days, urinary protein levels gradually decreased. Ultrastructural examinations showed glomerular damages such as significant decrease in slit pore number, a significant gradual increase in glomerular basement membrane thickness and podocyte hypertrophy on 5th and 15th days; besides significant increase in mesangial matrix. The first significant increases in phosphorylated and total STAT3 levels occurred in 5th day and 15th day groups respectively. These increases diminished in 25th day group. Regarding all the findings, it was deduced that STAT3 is one of the active factors in glomerular pathologies.
Proceedings, annual meeting, Electron Microscopy Society of America
Experiments points out that renomedullary interstitial cells (RIC) are responsible for antihypert... more Experiments points out that renomedullary interstitial cells (RIC) are responsible for antihypertensive function of kidney medulla, but functional roles of lipid granules (LG) of the cell in prostaglandin and renomedullary hormone synthesis are still being discussed. We searched, the relationship in between LG and PGE2 synthesis capacity of RIC in rats induced with a prostaglandin synthetase inhibitor (indomethacin). Three months old 6 Wis-tar rats used in control and experiment groups. Daily doses of 5 mg/kg indomethacin introduced orally to rats in experiment group for 12 days. PGE2 levels were determined in blood samples obtained from left renal vein (Tab.1). Electron microscopic specimens prepared from inner medulla of right kidneys. We caunted LG in 100 RIC of each rat (Tab.1). Frequency of LG groups in control and experiment groups are shown in (Tab.2).Observations in experiment group; increased cytoplasmic matrix density, mitochondrial swelling, both enlargement of GER and pe...
Totally 25 cases without any fetal anomaly, 10 with polyhydramnios, 10 with oligohydramnios and 5... more Totally 25 cases without any fetal anomaly, 10 with polyhydramnios, 10 with oligohydramnios and 5 with normal volume of amniotic fluid were taken into consideration. Their amnion covering the placenta and umbilical cord were examined under electron microscope. In the group with polyhydramnios the microvilli facing the amniotic cavity were denser in certain regions. The intercellular space was widened and the terminal bars were opened. Within the cells the number of vesicles were increased and there were large cysternas within these vesicles. It was postulated that the large cysternas found in the basal and apical parts of the cell were composed of macropinocytotic vesicles of the basal membrane. In the group with oligohydramnios the microvilli on the apical side were diminished. The intercellular space of the lateral side was narrowed. The electron density of the basal lamina was increased. The cellular structures were apparently reduced having just a few vesicles and lipid granules. Both in polyhydramnios and oligohydramnios the amniotic epithelium cells covering the placenta and umbilical cord are responsible for the transfer of the fluid into the amniotic cavity. Possibly they control the amount of fluid by reducing or increasing its passage.
Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed b... more Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.
This study aims to determine the potential renal protective effects of Opuntia ficus-indica (L.) ... more 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.
Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The t... more 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 72 nd 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.
Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3... more Recent studies showed that JAK/STAT pathway plays role in glomerular damages. The fact that STAT3 could be activated also by oxidative stress make Puromycin Aminonucleoside (PAN) Nephrosis model very appropriate for examination of STAT3 expression changes in glomerular pathology. Along with a control group, three PAN groups sacrificed on different days were formed by the i.p. injection of PAN for 5 consecutive days. Throughout the experiment, 24-hour-urines were collected on specific days and proteinuria levels were monitored. At the end of the experiments, tissue specimens were stained immunohistochemically for both total and phosphorylated STAT3 and evaluated subjectively. They were also examined ultrastructurally in transmission electron microscope. The proteinuria levels did not increase significantly on 5th day but showed a dramatic increase on 10th and 15th days. On 20th and 25th days, urinary protein levels gradually decreased. Ultrastructural examinations showed glomerular damages such as significant decrease in slit pore number, a significant gradual increase in glomerular basement membrane thickness and podocyte hypertrophy on 5th and 15th days; besides significant increase in mesangial matrix. The first significant increases in phosphorylated and total STAT3 levels occurred in 5th day and 15th day groups respectively. These increases diminished in 25th day group. Regarding all the findings, it was deduced that STAT3 is one of the active factors in glomerular pathologies.
Proceedings, annual meeting, Electron Microscopy Society of America
Experiments points out that renomedullary interstitial cells (RIC) are responsible for antihypert... more Experiments points out that renomedullary interstitial cells (RIC) are responsible for antihypertensive function of kidney medulla, but functional roles of lipid granules (LG) of the cell in prostaglandin and renomedullary hormone synthesis are still being discussed. We searched, the relationship in between LG and PGE2 synthesis capacity of RIC in rats induced with a prostaglandin synthetase inhibitor (indomethacin). Three months old 6 Wis-tar rats used in control and experiment groups. Daily doses of 5 mg/kg indomethacin introduced orally to rats in experiment group for 12 days. PGE2 levels were determined in blood samples obtained from left renal vein (Tab.1). Electron microscopic specimens prepared from inner medulla of right kidneys. We caunted LG in 100 RIC of each rat (Tab.1). Frequency of LG groups in control and experiment groups are shown in (Tab.2).Observations in experiment group; increased cytoplasmic matrix density, mitochondrial swelling, both enlargement of GER and pe...
Totally 25 cases without any fetal anomaly, 10 with polyhydramnios, 10 with oligohydramnios and 5... more Totally 25 cases without any fetal anomaly, 10 with polyhydramnios, 10 with oligohydramnios and 5 with normal volume of amniotic fluid were taken into consideration. Their amnion covering the placenta and umbilical cord were examined under electron microscope. In the group with polyhydramnios the microvilli facing the amniotic cavity were denser in certain regions. The intercellular space was widened and the terminal bars were opened. Within the cells the number of vesicles were increased and there were large cysternas within these vesicles. It was postulated that the large cysternas found in the basal and apical parts of the cell were composed of macropinocytotic vesicles of the basal membrane. In the group with oligohydramnios the microvilli on the apical side were diminished. The intercellular space of the lateral side was narrowed. The electron density of the basal lamina was increased. The cellular structures were apparently reduced having just a few vesicles and lipid granules. Both in polyhydramnios and oligohydramnios the amniotic epithelium cells covering the placenta and umbilical cord are responsible for the transfer of the fluid into the amniotic cavity. Possibly they control the amount of fluid by reducing or increasing its passage.
Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed b... more Puromycin aminonucleoside (PA) has been generally utilized as model of podocyte injury followed by massive proteinuria, severe damage on endocytotic activity of epithelial cells and postmodification of endocytosed compounds. However, total PA nephrosis (PAN) mechanism cannot be understood. We aimed to study glomerular function, foot process degeneration and transport pathways of podocytes in pre-proteinuria and acute PAN rats. Eighteen male Wistar albino rats were divided into three groups: control, pre-proteinuria and acute nephrosis groups (n=6). PA was injected into pre-proteinuria group for three times and acute group for nine times. Proteinuria levels in urine, creatinine and albumin levels in blood were detected 24 hours after PA injections. Renal cortex samples were prepared for transmission electron microscopy. Proteinuria levels in acute group significantly elevated, whereas creatinine clearance, serum albumin levels and urine volumes diminished compared to control and pre-proteinuria groups. In pre-proteinuria group, hypertrophy and structurally rich cytoplasm were detected only within podocytes. Acute group had various protein absorption granules secreted from podocyte cytoplasm to the urinary space through exocytosis after lysosomal digestion; but not observed in pre-proteinuria group. The number of slit pores in pre-proteinuria group decreased, particularly related to fusion of foot processes, subsequently leading to proteinuria. We concluded that foot process fusion begins prior to development of proteinuria although their serum albumin and creatinine clearance levels do not differ significantly. Additionally, we suggested that in acute PAN, first affected glomerular cells could be podocytes and there could be a correlation between glomerular function and number of slit pores.
This study aims to determine the potential renal protective effects of Opuntia ficus-indica (L.) ... more 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.
Transplantation is lifesaving and the most effective treatment for end-stage organ failure. The t... more 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 72 nd 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.
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