The combined effect of rosuvastatin and ischemic pre- or post-conditioning on myocardial ischemia-reperfusion injury in rat heart.

OBJECTIVE: To investigate the combined effect of rosuvastatin and ischemic preconditioning or postconditioning on ischemia-reperfusion injury in in vivo rat heart. MATERIALS AND METHODS: Ninenty-six male adult Wistar rats were randomly assigned to eight groups: Sham group, ischemia-reperfusion, rosuvastatin preconditioning, rosuvastatin postconditioning, ischemic preconditioning, ischemic postconditioning, ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups. Blood samples were taken for creatine kinase evaluation at selected time points. Six rats in each group were separated for either infarct size assessment or immunohistochemical staining with Bcl-2 antibody. RESULTS: The staining with Bcl-2 was significantly lower in groups Sham, ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups which is well correlated with the decrease in infarct size for the same groups. The creatine kinase enzyme levels were also reduced to their lowest levels in ischemic + pharmacologic preconditioning and ischemic + pharmacologic postconditioning groups. CONCLUSIONS: These findings suggest that enriching the composition of reperfusate with rosuvastatin along with ischemic preconditioning or postconditioning procedures at the opposite sides of ischemia may interact synergistically for protecting ischemic myocardium from reperfusion injury. The combined application of rosuvastatin with ischemic preconditioning or ischemic postconditioning may provide a new therapeutic option in clinical interventions when compared to single treatment with ischemic and rosuvastatin preconditioning or postconditioning.

Protective effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase in distant liver injury induced by renal ischemia-reperfusion in rats.

BACKGROUND AND AIMS: Renal ischemia followed by reperfusion causes remote liver injury. This research was planned to investigate whether 3-aminobenzamide (3-AB), has any preventive effect against distant liver injury triggered by renal IR. MATERIALS AND METHODS: Twenty four rats were randomly divided into three different groups Each group has 8 rats. The groups were as follows: (1) Sham operated group; (2) Renal ischemia-reperfusion (IR) group; (3) Renal IR+ 3-AB group. 3-AB (10 mg/kg) was given intraperitoneally 10 minute before reperfusion. At the end of study, the rats were sacrificed. Their liver tissues and serum samples were collected for measurement of malondialdehyde (MDA) levels, total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). RESULTS: Renal IR injury significantly increased Oxidative stress index (OSI) and MDA, TOS levels and significantly decreased PON-1 actvity and TAS, NO levels in serum and liver tissue (p < 0.05). Despite that, changes in these biochemical parameters related with IR injury were diminished by 3-AB administration (p < 0.05). CONCLUSIONS: The inhibition of PARP [Poly(ADP-Ribose)Polymerase] by 3-AB showed protective effects against distant liver injury triggered by renal ischemia-reperfusion by the ameliorating effects of 3-AB on oxidative stress.

Investigating the effect of the poly(ADP-ribose) polymerase inhibitor 5-aminoisoquinolinone and the Na⁺-H⁺ exchanger inhibitor zoniporide on isolated perfused rat hearts during ischemia-reperfusion injury.

The goal of this study was to investigate whether the combination of the Poly(ADP-ribose) polymerase inhibitor 5-aminoisoquinolinone (5-AIQ) and the Na+-H+ exchanger inhibitor zoniporide (ZN) provides increased protection against ischemia-reperfusion (I/R) injury. Rats were separated into 5 groups (n=8): Group 1: Control group, Group 2: I/R, Group 3: 5-AIQ, Group 4: ZN and Group 5: Mix (5-AIQ+ZN). Isolated rat hearts were subjected to 30 min of global ischemia, followed by 120 min of reperfusion using Langendorff's apparatus. In groups 3, 4 and 5, 5-AIO (7.5 µM/L) and ZN (50 nM/L) were added to Tyrode Solution after a stabilization period. The level of lactate dehydrogenase (LDH) was determined in the sample perfusate. Myocardial infarct size was determined using the triphenyltetrazolium chloride method. Heart tissues were stored to determine the malondialdehyde (MDA) content, total oxidant status (TOS) and total antioxidant status (TAS). Compared to the 5-AIQ and ZN groups, there was no notable difference in the LDH, MDA, TOS, TAS and hemodynamic parameters of the 5-AIQ+ZN group, but myocardial infarct size decreased significantly, as determined by volume and weight measurements. These results show that the combined use of Zoniporide and 5-Aminoisoquinolinone provides increased protection against I/R injury by reducing myocardial infarct size.

The insertion/deletion polymorphism in the ACE gene and chronic obstructive pulmonary disease.

An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.

Protective effect of ethyl pyruvate on liver injury in streptozotocin-induced diabetic rats.

BACKGROUND AND AIMS: Diabetes Mellitus, leading to an increase in oxidative stress, can cause liver damage. Our aim was to investigate the antioxidant effects of Ethyl Pyruvate (EP) on the liver tissue in diabetic rats. MATERIALS AND METHODS: Thirty-two Wistar albino rats were separated into four equal groups. Groups were assigned as follows: (1) Non-diabetic group; (2) EP-treated non-diabetic group; (3) diabetic group; and (4) EP-treated diabetic group. In order to induce diabetes mellitus, 45 mg/kg b.w. streptozotocin was administered intraperitoneally to the rats in groups 3 and 4. On the 3rd day, blood glucose was assessed. Rats with blood glucose levels higher than 300 mg/dl were considered to be diabetic. The EP solution was administered intraperitoneally at a dose of 50 mg/kg b.w. twice daily for 14 days to the rats in groups 2 and 4. The other rats were simultaneously given the same amount of Ringer's lactate solution intraperitoneally. Liver tissue was obtained for malondialdehyde (MDA) analyses and histopathological examination. RESULTS: In group 4, Total Antioxidant Status (TOS) and MDA levels were significantly lower as compared to group 3. Also, morphological abnormalities occurred in group 3 when compared with non-diabetic groups (groups 1 and 2), whereas the disorders resulting from diabetes improved significantly in group 4. CONCLUSIONS: These findings show that EP has protective effects against diabetes-induced liver injury.

Postsurgical complications in living-related liver donors.

From September 2001 until March 2007, we performed 127 living-donor liver transplantations in our transplantation center. Of 127 donors, 74 were men and 53 women, of overall mean donor age of 35.2 +/- 9.3 years (range, 20-56 years). Ninety-six (75.6%) were first-degree relatives, 18 (14.1%) were second-degree relatives, and 13 (10.3%) were spouses. We performed 34 (26.7%) left hepatic lobectomies, 33 (25.3%) left lateral segmentectomies, and 60 (48%) right hepatic lobectomies. The mean percentages of remnant to donor total liver volume for the right, left, and left-lateral lobectomies were 41.7%, 67.8%, and 75.1%, respectively. The mean length of patient postoperative hospital stay was 7.4 +/- 3.1 days (range, 3-33 days). There was no postoperative mortality. Ten complications occurred in 7 of the 127 donors (5.5%). Most complications were treated with radiologic interventions. In conclusion, donor safety should be the primary focus in living-donor liver transplantation. More experience, improved surgical techniques, and meticulous donor evaluation will help to minimize morbidity and mortality for living liver donors.

Tacrolimus-related seizure in the early postoperative period after liver transplantation.

The aim of this study was to analyze liver transplant patients who had tacrolimus (TAC)-related seizures at our institution during the early postoperative period. Between September 2001 and June 2006, liver transplantation (LT) was performed in 132 patients. All received a TAC-based immunosuppressive protocol after LT. Twelve (9%; 1 woman, 11 men; mean age 20 +/- 12 years; range, 12-49 years) of those 132 patients had a seizure during the first month. Three of these patients had received grafts from cadaveric donors and nine from living donors. All patients presented with generalized tonic-clonic seizures, and most had minor symptoms just hours before the attack. Blood TAC levels were within the therapeutic range, and there were no other factors that could have initiated a seizure at that time. Eleven patients were changed from TAC to cyclosporine (CsA), and one was switched to sirolimus. They also received antiepileptic therapy. All patients recovered and seizures disappeared. There were no nephrotoxicity or surgical complications related to drug conversion. Death (unrelated to seizure) occurred in one patient at 2 months after LT. Eleven patients are alive with good graft function at a mean follow-up of 20 +/- 19.7 months (range, 1-52 months). In conclusion, during the early posttransplant period, each neurologic disturbance, even a minor one, should alert the clinician, as it might be a warning sign of a coming seizure. These patients should be followed closely, and the clinician should not hesitate to do a drug conversion in suspicious cases.