Sebahattin Muhtaroglu

Role of Oxygen Free Radical Scavengers in Acute Renal Failure Complicating Obstructive Jaundice

Obstructive jaundice is associated with high morbidity and mortality. Major complications such as pulmonary dysfunction, renal failure and sepsis are frequently encountered. Recent studies and observations suggest that the free oxygen radicals (FORs) produced in obstructive jaundice may play a significant role in the etiopathogenesis of acute renal failure (ARF). Thirty rats were divided into three groups, as sham, control and treatment groups containing 10 rats each. Laparatomy was performed on each animal in the control and treatment groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection was begun on the first day of surgical procedure and repeated once a day during the following 5 days. The same procedure was performed with oxygen radical scavenger dimethyl sulfoxide (1.5 mg/kg/day i.p.) instead of saline in the treatment group. The rats were sacrificed on the 7th postoperative day. On the 7th postoperative day, the bilirubin, urea and creatinine levels of the control and treatment groups were significantly higher in comparison with the sham group (p < 0.01). Although there was no statistically significant difference between the bilirubin levels of the control and treatment groups (p > 0.05), the urea and creatinine levels in the treatment group were significantly lower (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and treatment groups were significantly lower than those of the sham group (p < 0.01), whereas renal and erythrocyte malondialdehyde (MDA) levels were significantly higher (p < 0.01). Although SOD and GSH-Px levels did not differ significantly between the treatment and control groups (p > 0.05), renal and erythrocyte MDA levels of the treatment group were significantly lower than those of the control group (p < 0.01). The histopathological scores were significantly higher in the control and treatment groups (p < 0.01); there was no significant difference between the control and treatment groups (p > 0.05). FORs seem to play a significant role in the etiopathogenesis of renal failure in obstructive jaundice. Antioxidant treatment may decrease oxidative damage due to FORs and may prevent renal failure.

Twenty two weeks of transdermal estradiol increases sex hormone-binding globulin in surgical menopausal women

OBJECTIVE To compare the effects of continuous noncombined transdermal estradiol versus oral conjugated estrogen on serum sex hormone-binding globulin (SHBG) levels prior to and during the 10th and 22nd weeks of therapy in patients with surgical menopause. STUDY DESIGN Open, comparative trial. Patients were consecutively assigned to three groups: group 1 (n = 18) received continuous transdermal estradiol (0.050 mg/day), group 2 (n = 18) continuous oral conjugated estrogens (0.625 mg/day), whereas group 3 (n = 15) received no treatment. Serum SHBG levels were determined before treatment and after 10 and 22 weeks of treatment. RESULTS Serum SHBG increased significantly with oral conjugated estrogens at 10 (p < 0.01) and 22 weeks (p < 0.01) compared with baseline. With transdermal estrogens there was a much smaller increase of SHBG. At 22 weeks, this increase was significant compared with baseline (p < 0.05), but not compared with the control group (p > 0.05). CONCLUSION Transdermal estrogen has no effect on SHBG, whereas oral conjugated estrogens causes considerable increase.

Portosystemic Shunt Prevents Apoptosis in Rat Intestinal Mucosa Caused by Total Hepatic Ischemia

Background: Prolonged splanchnic congestion due to total hepatic ischemia (THI) has been shown to induce damage to the intestinal mucosa. The present study was conducted to examine whether the protective effect of portosystemic shunt (PSS) can be seen on apoptosis of intestinal mucosa in a rat model of THI. Methods:Adult male Wistar rats were divided into the following 3 groups: control group; the THI group underwent THI for 30 min, and the PSS group was subjected to THI for 30 min with PSS. Rats were killed after 1, 2, and 6 h of reperfusion. For each time point, levels of serum liver enzymes, intestinal morphology, malondialdehyde (MDA) contents and DNA fragmentation in intestinal tissue were determined. In addition, the 7-day survival rate was measured. Results: The 7-day survival rate of THI group remained at 50%, whereas that of PSS group was significantly higher at 90% (p < 0.01). Serum AST and ALT levels of the THI and PSS groups rapidly increased after reperfusion, reaching peak values at 2 h. MDA levels after 1 and 2 h of reperfusion in the THI group were significantly increased as compared with the control group (p < 0.001). Increases in the percentage of fragmented DNA peaked 1 h after reperfusion in the THI group. PSS resulted in the reduction of DNA fragmentation and preserved the macroscopic and microscopic appearance of the intestinal mucosa. Conclusions: Splanchnic congestion due to portal occlusion increased apoptosis in the rat intestinal mucosa. PSS is very effective in counteracting the principal negative effects of total hepatic ischemia.

The Effects of Dimethylsulfoxide in Experimental Obstructive Jaundice

Abstract Material and methods: Thirty rats were divided into three groups, as sham, control and DMSO groups. Laparatomy was performed on each animal in the control and DMSO groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection (1.5 mg/kg/intraperitoneally (ip)) was begun on the first day of surgical procedure and repeated once a day for the next 5 days. The same procedure was performed with DMSO (1.5 mg/kg/ip) instead of saline in the DMSO group. The rats were sacrificed on the postoperative seventh day, at which time venous blood and liver tissue specimens were taken. Main outcome measurements: On the 7th postoperative day, the bilirubin, AST, ALT, ALP and GGT levels of the control and DMSO groups were significantly higher in comparison with the sham group (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and DMSO groups were significantly lower than those of the sham group (p < 0.01), but there was no statistical difference between the two groups (p > 0.05). Erythrocyte and liver malondialdehyde (MDA) levels in the control and DMSO groups were significantly higher compared with the sham group (p < 0.01). However, the MDA levels were significantly lower in the DMSO group compared to the control group (p < 0.01). Conclusion: It is stated that free oxygen radicals seem to play a role in the liver tissue injury, secondary to obstructive jaundice. In our experimental study, exogenic DMSO seems to have decreased lipid peroxidation and to have improved some of the parameters of liver tissue injury due to the obstructive jaundice in rats.

Effects of amrinone in an experimental model of hepatic ischemia-reperfusion injury.

BACKGROUND During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischemia-reperfusion (IR) injury. Recent studies suggest that type 3 phosphodiesterase inhibitors may have a beneficial effect on liver IR injury. The aim of this study was to investigate whether amrinone, a type 3 phosphodiesterase inhibitor, could have a protective effect on liver having experimental liver IR injury. MATERIALS AND METHODS Sixty Wistar albino rats were randomly divided into three groups. The IR and amrinone groups were subjected to 1 h total hepatic ischemia, followed by 2 h of reperfusion. The sham group underwent midline laparotomy only. Amrinone 10 microg/kg/min was infused to the amrinone group during the 3 h of the IR period. Histopathological examination, biochemical liver function, and liver adenosine triphosphate concentration after reperfusion and survival rate on the seventh day after the IR insult were recorded. RESULTS Serum aspartate aminotransferase, alanine aminotransferase, lactic dehydrogenase levels, and histological damage scores in the amrinone and IR groups were significantly higher compared with the sham group (P < 0.01). However, all of these values were significantly lower in the amrinone group than in the IR group (P < 0.05). Liver adenosine triphosphate levels and the rat survival rate in the amrinone and IR groups were significantly lower than those in the sham group (P < 0.01). However, these values were significantly higher in the amrinone group compared to those in the IR group (P < 0.01). CONCLUSIONS These results suggest that amrinone plays a significant role in the protection of liver against IR injury and that this treatment may be a novel pharmacological agent for safe and efficient liver surgery.

Role of Granulocyte-Macrophage Colony-Stimulating Factor on Apoptosis Induced by Ischemia-Reperfusion in the Intestinal Epithelium

Background: To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on ischemia-reperfusion-induced apoptosis in the intestinal epithelium. Methods: In this study, 50 male Wistar albino rats were used. After midline laparotomy superior mesenteric artery (SMA) was identified only in the sham group, while 60 min of ischemia and 2 h of reperfusion were performed in the control group. In the treatment groups, after 15, 30 and 60 min of ischemia, respectively, 1 µg/kg GM-CSF was administered subcutaneously, followed by 2 h of reperfusion. Malondialdehyde (MDA), campothecin (CAM), an indicator of DNA fragmentation, and histopathology were evaluated in the intestinal mucosa. Results: Tissue MDA levels were found significantly high in all groups at various times of ischemia and 2 h of reperfusion compared with the sham group (p < 0.001). Administration of GM-CSF following 60 min of ischemia caused a significant increase in the MDA levels compared with the control group (6,430 ± 725 vs. 4,174 ± 565 nmol/g protein for jejunum. 7,576 ± 618 vs. 4,938 ± 809 nmol/g protein for ileum, p < 0.05). Intestinal ischemia and reperfusion resulted in a significant increase in tissue CAM levels (p < 0.05). The highest CAM value was found in the group in which 60 min of ischemia and 2 h of reperfusion were performed (50 ± 3.2 ng/ml for jejunum, 52.8 ± 2.7 ng/mg for ileum). Compared with the control group, GM-CSF administration following 1 h of ischemia aggravated the tissue injury. Conclusions: Apoptosis was induced in the small intestine by ischemia-reperfusion. GM-CSF increased the apoptosis of intestinal epithelial cells and exacerbated mucosal injury due to ischemia-reperfusion.