Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Comparison of the effects of losartan, captopril, angiotensin II type 2 receptor agonist compound 21, and MAS receptor agonist AVE 0991 on myocardial ischemia-reperfusion necrosis in rats.

Myocardial ischemia may occur as a result of pathophysiological and therapeutical applications such as atherosclerosis, thromboembolism, percutaneous transluminal coronary angioplasty, coronary artery bypass, and transplantation. In this study, we aimed to compare the effects of angiotensin (Ang) II type 2 (AT2 ) selective receptor agonist Compound 21 (C21), MAS receptor agonist AVE 0991, Ang II type 1 (AT1 ) selective receptor blocker losartan, and Ang-converting enzyme inhibitor captopril on haemodynamic parameters and infarct size on myocardial ischemia/reperfusion (MI/R)-induced necrosis in rats. To induce necrosis in the heart of rats, reperfusion for 2 h following ischemia for 30 min to the descending branch of the left main coronary artery was achieved. C21 (0.03 mg/kg), AVE 0991 (576 µg/kg), losartan (2 mg/kg), and captopril (3 mg/kg) were administered as an intravenous infusion at 10 min before and throughout the ischemia. Then, the infarct size and risk area were calculated from the heart. The percentage of myocardial infarct size to area at risk ratio (%IS/AR) of groups was Control (MI/R) group: 48.9 ± 8.8%; C21 group: 31.1 ± 7.8%; AVE 0991 group: 29.9 ± 4.8%; C21 + AVE 0991 group: 28.2 ± 3.3%; Losartan + AVE 0991 group: 30.8 ± 5.8%; Captopril + AVE 0991 group: 31.7 ± 7.7%. %IS/AR of the drug-treated groups decreased significantly when compared to the MI/R group (P < 0.05). Our results indicate that the importance of AT1 , AT2 , and MAS receptors in the MI/R injury. Inhibition of Ang II formation by captopril, blockade of AT1 receptor with losartan, and stimulation of AT2 receptor with C21 and MAS receptor with AVE 0991 showed beneficial effects by reducing infarct size.

Acute and Subacute Effects of Low Versus High Doses of Standardized Panax ginseng Extract on the Heart: An Experimental Study.

Panax ginseng is commonly used in Chinese medicine and Western herbal preparations. However, it has also been recently noted to be associated with some cardiac pathologies-including cardiogenic shock due to acute anterior myocardial infarction, trans-ischemic attack, and stent thrombosis. This study was aimed to elucidate acute and subacute effects of the low and high doses of standardized Panax ginseng extract (sPGe) on cardiac functions. Rats were randomly assigned to control group, acute low-dose group (ALD), subacute low-dose group (SALD), acute high-dose group (AHD), and subacute high-dose group (SAHD). The cardiac effects of sPGe were evaluated using hemodynamic, biochemical, echocardiographic, genetic, and immunohistopathologic parameters. Mean blood pressures were significantly lower in all sPGe-treated groups compared with the control group. Troponin I and myoglobin levels were increased in the SALD, AHD, and SAHD groups. Mitral E-wave velocity was reduced after sPGe administration in all the groups. Acidophilic cytoplasm and pyknotic nucleus in myocardial fibers were observed in AHD and SAHD groups. Cu/Zn-SOD1 gene expressions were significantly higher in the sPGe-treated groups whereas caveolin 1 and VEGF-A gene expressions were not changed. According to our results, sPGe may have a potential effect to cause cardiac damage including diastolic dysfunction, heart failure with preserved ejection fraction, and reduction of blood pressure depending on the dose and duration of usage. Healthcare professionals must be aware of adverse reactions stemming from the supplementation use, particularly with cardiac symptoms.

Protective and therapeutic effects of dexpanthenol on isoproterenol-induced cardiac damage in rats.

The purpose of the study was to explore the protective and therapeutic effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage. Forty rats were distributed into four groups: group I (Control); group II (ISO); ISO (150 mg/kg/day) was given to rats once a day for 2 consecutive days with an interval of 24 h; group III (DEX+ISO): DEX (250 mg/kg) was applied 30 min before the first ISO administration and continued in the next two days after second ISO administration; group IV (ISO+DEX): After the ISO treatment at 1st and 2nd days, DEX was given at 3rd and 4th days. Rats were monitored for mean arterial blood pressure (BP), heart rate, oxygen saturation (%SO2 ), and electrocardiography (ECG). Heart tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), total oxidant status (TOS); total antioxidant capacity (TAC), oxidative stress index (OSI), and caspase-3 were determined. BP and SO2 values indicated a significant decrease in the ISO group. Also, T wave negativity was observed in 6 of 10 rats, SOD, CAT, and GPX levels were significantly lower in ISO group than control group. ISO administration increased TOS and OSI levels, whereas DEX treatment significantly reduced these parameters. Also, ISO-induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization whereas these histological damages were significantly decreased in ISO+DEX and DEX+ISO groups when compared to the ISO group. This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity.

Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats.

Preventive and/or therapeutic interventions for ischemic heart disease have gained considerable attention worldwide. We investigated the mechanism(s) underlying cardioprotection of apocynin (APO) and whether it attenuates isoproterenol (ISO)-induced myocardial damage in vivo. Thirty-two male Wistar Albino rats were randomised into four groups (n = 8 for each group): Group I (Control); Group II (ISO), ISO was given intraperitoneally (ip) (150 mg/kg/d) daily for 2 consecutive days; Group III (APO + ISO), APO was applied ip 20 mg/kg 30 min before the first ISO administration and continued for the next 2 d after the second ISO administration; Group IV (ISO + APO), after the ISO treatment on days 1 and 2, 20 mg/kg APO was given ip on days 3 and 4. Cardioprotective effects of APO were evaluated by biochemical values, histopathological observations and the antiapoptotic relative proteins. Mean blood pressure, heart rate, and electrocardiography (ECG) were also monitored. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), caspase-3 and connexin 43 levels were determined. Major ECG changes were observed in the ISO-treated rats. MDA, TOS, OSI and creatine kinase levels decreased and SOD, CAT, GSH and TAC levels increased, indicating that APO reduced cardiac injury and oxidative stress compared with controls. APO also decreased the number of cardiomyocytes with pyknotic nuclei, inflammatory cell infiltration, intracytoplasmic vacuolisation and myofibrils. APO provides preventive and therapeutic effects on ISO-induced myocardial injury in rats by inhibiting reactive oxygen species production, blocking inflammation and enhancing antioxidant status.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

Effect of endogen-exogenous melatonin and erythropoietin on dinitrobenzene sulfonic acid-induced colitis.

Inflammatory bowel disease has been linked to elevated T cells. Excessive production of reactive oxygen species and apoptosis are known to be accompanied by intestinal inflammation. This study was designed to investigate the effects of melatonin (MEL) and erythropoietin (EPO), which is a known anti-inflammatory and antiapoptotic agent, in dinitrobenzene sulfonic acid (DNBS)-induced colitis in pinealectomized (Px) rats. In microscopically results, epithelial and goblet cell loss, absence of crypts, and increased colonic caspase-3 activity were observed in the DNBS group. Also, in flow cytometric analysis, the percentage of CD4+ T cells was highest in the DNBS group. Treatment with MEL or EPO had a curative effect on DNBS-induced colitis. The MEL + EPO groups showed significantly greater improvement when compared with the other treatment groups. Our results indicate that the combination of EPO and MEL may exert more beneficial effects than either agent used alone.

Protective effect of infliximab on ischemia/reperfusion-induced damage in rat kidney.

OBJECTIVE: To investigate the protective effect of infliximab on ischemia-reperfusion (I/R) injury of the rat kidney. METHODS: Twenty-eight male Wistar albino rats were divided into four groups: sham-operated, I/R, I/R with infliximab administered before ischemia [I/R + infliximab (bi)], and I/R with infliximab administered before reperfusion [I/R + infliximab (br)]. After a right nephrectomy to produce damage, the left renal vessels were occluded for 60 min, followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin-eosin (H&E)-stained and periodic acid-Schiff (PAS) sections. RESULTS: The MDA and MPO levels in the I/R group were significantly higher than in the other groups (p < 0.05), and the SOD and GSH levels in the I/R + infliximab (bi) and I/R + infliximab (br) groups were significantly higher than in the I/R group (p < 0.05). However, histological examination revealed that the I/R + infliximab (bi) group and the I/R + infliximab (br) group had significantly fewer tubular changes and interstitial inflammatory cell infiltration than the I/R group. CONCLUSION: These results show that infliximab may protect against I/R injury in the rat I/R model.

Intravesical hyaluronic acid and chondroitin sulfate alone and in combination for urinary tract infection: assessment of protective effects in a rat model.

OBJECTIVE: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. METHODS: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. RESULTS: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 × 10(3) cfu/mL) and chondroitin sulfate (1 × 10(4) cfu/mL) groups relative to the control group (5 × 10(4) cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 × 10(2) cfu/mL; P < 0.05). In the bladder tissues, statistically significant decreases in median bacterial growth rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium damage decreased in the treatment groups. However, this effect was prominent in hyaluronic acid + chondroitin sulfate group. CONCLUSION: Our experimental findings show that the hyaluronic acid + chondroitin sulfate combination has a potential benefit in reducing the bacterial load in urine and the thickness of the transitional epithelium.

Effects of electromagnetic radiation from 3G mobile phone on heart rate, blood pressure and ECG parameters in rats.

Effects of electromagnetic energy radiated from mobile phones (MPs) on heart is one of the research interests. The current study was designed to investigate the effects of electromagnetic radiation (EMR) from third-generation (3G) MP on the heart rate (HR), blood pressure (BP) and ECG parameters and also to investigate whether exogenous melatonin can exert any protective effect on these parameters. In this study 36 rats were randomized and evenly categorized into 4 groups: group 1 (3G-EMR exposed); group 2 (3G-EMR exposed + melatonin); group 3 (control) and group 4 (control + melatonin). The rats in groups 1 and 2 were exposed to 3G-specific MP's EMR for 20 days (40 min/day; 20 min active (speech position) and 20 min passive (listening position)). Group 2 was also administered with melatonin for 20 days (5 mg/kg daily during the experimental period). ECG signals were recorded from cannulated carotid artery both before and after the experiment, and BP and HR were calculated on 1st, 3rd and 5th min of recordings. ECG signals were processed and statistically evaluated. In our experience, the obtained results did not show significant differences in the BP, HR and ECG parameters among the groups both before and after the experiment. Melatonin, also, did not exhibit any additional effects, neither beneficial nor hazardous, on the heart hemodynamics of rats. Therefore, the strategy (noncontact) of using a 3G MP could be the reason for ineffectiveness; and use of 3G MP, in this perspective, seems to be safer compared to the ones used in close contact with the head. However, further study is needed for standardization of such an assumption.

Dose-dependent protective effect of ivabradine against ischemia-reperfusion-induced renal injury in rats.

BACKGROUND/AIMS: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats. METHODS: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6-6 mg/kg ivabradine; and groups 5 and 6, sham+0.6-6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined. RESULTS: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels. CONCLUSION: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.

Effects of captopril and angiotensin II receptor blockers (AT1, AT2) on myocardial ischemia-reperfusion induced infarct size.

The renin-angiotensin system (RAS) plays a major role in regulating the cardiovascular system, and disorders of the RAS contribute largely to the cardiac pathophysiology, including myocardial ischemia-reperfusion (MI/R) injury. Two subtypes of angiotensin II (Ang II) receptors have been defined on the basis of their differential pharmacological properties. The current study was undertaken to address the question as to whether the inhibition of the angiotensin converting enzyme (ACE) by captopril and the AT1 and AT2 receptor blockers losartan and PD123319 modulate MI/R-induced infarct size in an in vivo rat model. To produce necrosis, a branch of the descending left coronary artery was occluded for 30 min followed by two hours of reperfusion. ECG changes, blood pressure, and heart rate were measured during the experiment. Captopril (3 mg/kg), losartan (2 mg/kg), and PD123319 (20 µg/kg/min) were given in an IV 10 min before ischemia and were continued during the ischemic period. The infarcted area was measured by TTC staining. The volume of infarct and the risk zone was determined by planimetry. Compared to the control group (55.62±4.00%) both captopril and losartan significantly reduced the myocardial infarct size (30.50±3.26% and 37.75±4.44%), whereas neither PD123319 nor PD123319+losartan affected the infarct size volume (46.50±3.72% and 54.62±2.43%). Our data indicates that captopril and losartan exert cardioprotective activity after an MI/R injury. Also, infarct size reduction by losartan was halted by a blockade of the AT2 receptor. Therefore, the activation of AT2 receptors may be potentially protective and appear to oppose the effects mediated by the AT1 receptors.

Beneficial effects of apricot-feeding on myocardial ischemia-reperfusion injury in rats.

The present study was undertaken to evaluate the cardio-protective potential of apricot-feeding in the ischemia-reperfusion (I/R) model of rats in vivo. Rats were divided into three groups of 12 rats each. Group 1 was fed with a standard rat chow, groups 2 and 3 were fed with a standard rat chow supplemented with 10% or 20% dried apricot during 3 months before the beginning of I/R studies. To produce I/R, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Infarct sizes were found significantly decreased in 10% (55.0 +/- 4.3%) and 20% (57.0 +/- 2.9%) apricot-fed groups compared to control group (68.7 +/- 2.0%). Light and electron microscopic evaluations of hearts also demonstrated similar beneficial effects on I/R injury in apricot-fed both groups. Total phenolic contents, DPPH radical scavenging and ferric-reducing power as in vitro antioxidant capacities of rat chows were significantly increased after supplementation with apricot for each ratio. Cu, Zn Superoxide dismutase (Cu, Zn SOD) and catalase (CAT) activities were increased, and lipid peroxidation was decreased significantly in the hearts of 20% apricot-fed group after I/R. In conclusion, we clearly demonstrated in vivo cardio-protective activity of apricot-feeding related to its antioxidant phenolic contents in rats subjected to myocardial I/R.

Assessment of myoelectrical signal parameters in estrogen, progesterone, and human chorionic gonadotropin administered in nonpregnant rat myometrium after ovariectomy.

OBJECTIVE: To investigate the correlation of myoelectrical signals with spontaneous contractile events and physiological states in the nonisolated uterine horn of rats. DESIGN: In vivo uterine myoelectrical activity recording study. SETTING: Animal and pharmacology laboratory at Inonu University. ANIMAL(S): Thirty-six female Wistar albino rats. INTERVENTION(S): Six animals were not castrated and served as a sham-operated control group; the other 30 were ovariectomized (OVX) and put into groups: unbiased OVX subjects, estrogen (E)-biased OVX subjects, P-biased OVX subjects, E-plus-P-biased OVX subjects, and hCG-biased OVX subjects. An MP100 A-CE was used for data acquisition, and a personal computer was used for processing. MAIN OUTCOME MEASURE(S): Besides the temporal, spectral, and joint time-frequency (spectrotemporal) analysis, some quantitative measures such as standard deviation and mark to space power ratios of myoelectrical signals were measured. RESULT(S): Progesterone, E, and hCG administration down-regulated the power and contraction frequency of the uterine electrical signal. The spectral concentrations that occurred around the 0.9, 0.35, and 0.7 Hz frequency ranges may be distinguishing characteristics for P, E, and hCG, respectively. CONCLUSION(S): Based on the obtained results, uterine contractions change with ovariectomy and administration of hormones. Progesterone, E, and hCG particularly prolong the quiescent periods of the uterus by reducing the frequency of uterine contractions as well as the power of the myoelectrical activity. Individual or combined use of P, E, or hCG might favor quiescence of the uterine muscle and the maintenance of pregnancy.

Investigating the protective effect of melatonin on liver injury related to myocardial ischemia-reperfusion.

BACKGROUND: An animal model of myocardial ischemia-reperfusion (MI/R) was used to test the hypothesis that free radicals released with MI/R have hazardous effects on liver through remote organ injury. MATERIAL/METHODS: Twenty-one rats were divided into three groups: sham-treated, MI/R, and MI/R+melatonin. To produce MI/R, a branch of the left coronary artery was occluded for 30 min followed by two hours of reperfusion. Melatonin or vehicle was given 10 min before ischemia. At the end of the study, liver tissue was obtained for biochemical determination. The false discovery rate (FDR) is explained and was used for multiple comparisons of the groups' means. RESULTS: Compared with the sham group, MI/R significantly decreased glutathione (GSH) content and increased levels of nitric oxide (NO) and malondialdehyde (MDA). Melatonin administration significantly increased GSH levels and decreased the levels of NO and MDA compared with the MI/R group. CONCLUSIONS: Melatonin could prevent liver damage due to its strong antioxidant and free radical scavenger effects. Therefore, melatonin may have beneficial effects on remote organ injury such as MI/R-induced liver disorders.

Protective effects of melatonin on renal failure in pinealectomized rats.

AIM: The purpose of the current study was to investigate the effects melatonin on renal function. METHODS: The histological appearance of the kidney and malondialdehyde, nitric oxide, glutathione and superoxide dismutase contents were determined. Serum creatinine and blood urea nitrogen levels were also assayed. Rats were divided as: Sham, pinealectomized (Px) and pinealectomized and treated with melatonin. RESULTS: In Px group, malondialdehyde and nitric oxide levels were elevated when compared with the sham group. The Px group exhibited reduced superoxide dismutase activity and glutathione content. All of these harmful changes were restored by melatonin. Melatonin also ameliorated serum creatinine and blood urea nitrogen levels related to renal injury. The score for glomerular, tubular and interstitial changes was significantly higher in the Px group. Melatonin supplementation significantly reduced these parameters. CONCLUSIONS: This protective effect may be associated with both melatonin's lipophilic and hydrophilic effects, thus providing on-site protection against free radical mediated damage.

Beneficial effects of caffeic acid phenethyl ester (CAPE) on the ischaemia-reperfusion injury in rat skin flaps.

BACKGROUND: Reperfusion injury is a phenomenon that occurs when tissues are subjected to ischaemia for a variable period of time, after which they are reperfused. Many factors have been implicated in the cause of reperfusion injury including free radicals and neutrophils. Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE) is an active component of propolis from honeybee; it has anti-inflammatory and immunomodulatory properties, and protective effects against ischaemia-reperfusion (I/R) injury. We investigated the effects of CAPE on the survival of skin flaps in the rat. MATERIALS AND METHODS: Eighteen Wistar rats were used, and randomly divided into three groups (n=6 rats each group): the control group (Group 1), ethanol group (Group 2), and CAPE group (Group 3). A caudally based rectangular flap, 3x10 cm in size, was elevated on the back of the rat, according to the method described by Khouri and colleagues. The flap was sutured back into its original place. In the control group, saline 0.2 ml/day was given intraperitoneally (i.p.). Five percent ethanol 0.2 ml/day was administered i.p. in the ethanol group, and CAPE 50 micromol/kg/day i.p. in the CAPE group. To observe the effects of CAPE, levels of malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Flap viability was evaluated seven days after the initial operation, measuring necrotic areas of flaps and total flap areas. RESULTS: MDA and NO levels were significantly decreased in CAPE group; and however, GSH, GSH-Px, and SOD enzyme activities were significantly increased in CAPE group. We believed that the CAPE had beneficial effects to improve the survival of skin flaps since it has antioxidative and anti-inflammatory properties, and protective effects against I/R injury.

Renal damage in rats induced by myocardial ischemia/reperfusion: Role of nitric oxide.

BACKGROUND: It has been demonstrated that myocardial ischemia/reperfusion (MI/R) causes renal damage. However, the mechanism underlying this damage in kidneys during revascularization of myocardium is unclear. Direct renal ischemia/reperfusion has been implicated in the induction of inducible nitric oxide synthase (iNOS) that leads to increase production of nitric oxide (NO). Recently, excessive production of NO has been found to be involved in causing renal injury by formatting peroxinitrite (ONOO(-)). The aim of this study was to investigate whether NO has a role in this damage, using aminoguanidine (AMG), a known iNOS inhibitor and an antioxidant, in rats undergoing MI/R. METHODS: Male Wistar rats were used for the experiments (n = 7 each group). In the MI/R group, the left coronary artery was occluded for 30 min and then reperfused for 120 min; the same procedure was used for the AMG group, with the additional step of AMG (200 mg/kg) administered 10 min prior to ischemia. A control group underwent sham operation. At the end of the reperfusion period, all rats were killed and their kidneys removed for biochemical determination and histopathological analysis. RESULTS: Myocardial ischemia/reperfusion in the rat kidney was accompanied by a significant increase in malondialdehyde and NO production, and a decrease in glutathione content. Administration of AMG reduced malondialdehyde and NO production and prevented depletion of glutathione content. These beneficial changes in the biochemical parameters were also associated with parallel changes in histopathological appearance. CONCLUSION: These findings suggest that MI/R plays a causal role in kidney injury and AMG exerts renal-protective effects, probably by inhibiting NO production and antioxidant activities.

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats.

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.

Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment.

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.