Osman Gökalp

Increased Caspase-3 Immunoreactivity of Erythrocytes in STZ Diabetic Rats

Eryptosis is a term to define apoptosis of erythrocytes. Oxidative stress and hyperglycemia, both of which exist in the diabetic intravascular environment, can trigger eryptosis of erythrocytes. In this experimental study, it is presented that the majority of erythrocytes shows caspase-3 immunoreactivity in streptozocin- (STZ)-induced diabetic rats. Besides that, caspase-3 positive erythrocytes are aggregated and attached to vascular endothelium. In conclusion, these results may start a debate that eryptosis could have a role in the diabetic complications.

The protective effects of caffeic acid phenethyl ester in isoniazid and ethambutol-induced ocular toxicity of rats

Abstract Purpose: This study intended to examine the effect of caffeic acid phenethyl ester (CAPE) on isoniazid (INH) and/or ethambutol (ETM)-induced retina and optic nerve toxicity in a rat model. Methods: This study included eight groups, each containing 10 rats. The groups were Control, INH, ETM, CAPE, INH+CAPE, ETM+CAPE, INH+ETM and INH+ETM+CAPE. Rats were given orally 50 mg/kg/d of INH and 50 mg/kg/d of ETM in tap water for 30 d. 10 μmol/kg of CAPE were intraperitoneally injected for 30 d. The first dose of CAPE was given 24 h before the INH and ETM treatment and continued until sacrifice. Control group was given only tap water for 30 d. Rats were anaesthetized and sacrificed on the 30th day of experiment. Superoxide dismutase (SOD) activities, malondialdehyde (MDA), total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the retinal ganglion cell (RGC) count. In addition, CAPE, INH and ETM interaction with SOD isoforms were calculated in silico. Results: The SOD activity and TAS levels were found significantly higher in CAPE-treated groups compared to INH and/or ETM-treated groups (p < 0.0001). But the MDA, and TOS levels were significantly lower in CAPE-treated groups (p < 0.0001). The mean RGC count is significantly decreased in INH, ETM and INH+ETM groups compared with INH+CAPE, ETM+CAPE and INH+ETM+CAPE groups, respectively (p values 0.001, 0.042, and 0.001 respectively). Besides, in silico calculations showed that binding affinity of CAPE to SOD isotypes was higher than that of INH and ETM. Conclusion: This study demonstrates that CAPE treatment may decrease the oxidative stress in the retina and optic nerve of INH- and ETM-treated rats and may prevent RGC loss. As an underlying mechanism, CAPE and SOD interaction seems crucial for alleviation of ocular oxidative stress and RGCs toxicity.

The protective role of caffeic acid phenethyl ester against streptomycin ototoxicity.

OBJECTIVE The aim of this experimental study was to investigate the efficacy of caffeic acid phenethyl ester (CAPE) in the prevention of streptomycin-induced ototoxicity. MATERIALS AND METHODS Thirty-two adult Wistar albino rats were divided into 4 groups: control (n = 8), streptomycin (n = 8), CAPE (n = 8), and streptomycin + CAPE (n = 8). Rats were tested with distortion product otoacoustic emissions (DPOAEs) before drug administration. The animals in all groups were killed under general anesthesia on the 45th day following last DPOAE measurements. Hearing results were analyzed statistically to determine differences in amplitudes of DPOAE. Also, the cochleas of each rat were evaluated by histopathological and immunohistochemical examination. RESULTS Significant difference was not observed in cochlear hair cells in the control and CAPE groups. In the streptomycin group, severe degeneration of hair cells and increased apoptotic cells were observed. In the streptomycin + CAPE group, although some deteriorations were observed, hair cells were mostly preserved. The DPgram of the streptomycin and streptomycin + CAPE groups was significantly deteriorated (P < .05). The analysis of the DPgram results revealed statistically significant differences between the groups of streptomycin and streptomycin + CAPE (P < .05). CONCLUSIONS Caffeic acid phenethyl ester treatment attenuated hair cells injury in the inner ear, possibly via its antioxidant effect. Prophylactic administration of CAPE for streptomycin ototoxicity ameliorated hearing deterioration in rats.

Histopathologic results of long-term sildenafil administration on rat inner ear.

OBJECTIVES Sildenafil, a selective inhibitor of phosphodiesterase type 5, is widely used for the treatment of erectile dysfunction. Although cochlear effects of phosphodiesterase type 5 inhibitors remain still unclear because of inadequate data, some evidence that recently emerged indicates that these medications may be responsible for hearing impairment. In the present study, we aimed to examine the histopathologic effects of long-term sildenafil use on the cochlea in a rat model. METHODS The study was performed with adult male Wistar albino rats. The control group was fed on standard laboratory diet. The study group was applied orally with sildenafil therapy, 1.5 mg/kg once a day for 45 days. Rats were anesthetized and decapitated. Each temporal bone was dissected, and the cochleas were removed en bloc. The inner-ear biopsy specimens were examined histologically with hematoxylin and eosin and caspase 3 immunoreaction under light microscopy. RESULTS Hematoxylin and eosin staining showed no distinctive difference between the control group and the sildenafil group. With immunohistochemical examination, caspase 3 immunoreactivity was observed in the sildenafil group. In the control group, caspase 3 immunoreactivity was not observed. CONCLUSIONS The caspase 3 immunoreactivity in the sildenafil group was strongly associated with an increase in apoptotic events in the cochlea. Long-term use of sildenafil can cause hearing impairment through increased apoptosis.

Routine enzymes in the monitoring of type 2 diabetes mellitus.

We examined the relationships of glucose and HbA1c levels with the routinely screened serum enzyme activities in type 2 diabetes mellitus, and we designed an in vitro study to evaluate the direct effect of glucose levels on enzyme activities. The study was performed on a consecutive series of outpatients with type 2 diabetes who were followed up at Dicle University Medical Faculty Hospital from May 2009 to May 2010 for the first time. Effects of aspartate transaminase, aminotransferase, gamma‐glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities, glucose and HbA1c levels and in vitro glucose (492, 287, 184, 131, 82 mg dl−1, respectively) on enzymes were determined. The patients were categorized on the basis of glucose and HbA1c levels and grouped according to a range of values. In patients with high HbA1c levels (>10.1%), ALP, GGT activities and creatine kinase (CK)‐MB/CK (p = 0.008, 0.026, 0.014) ratio were increased significantly when compared with those in the control group. In patients with high glucose levels (>200 mg dl−1), ALP, GGT activities and CK‐MB/CK ratio (p = 0.003, 0.001, 0.001) were increased significantly when compared with those in the control group. Glucose, which was added to serum in different concentrations in vitro, did not directly affect enzyme activities such as ALP, GGT and CK. We concluded that increased glucose levels could damage the liver and the heart muscle cells. Monitoring of blood glucose levels is a more valuable parameter than monitoring HbA1c in the momentary evaluation of diabetes. Copyright

The effects of caffeic acid phenethyl ester in acute methanol toxicity on rat retina and optic nerve

Abstract Purpose: We aimed to test caffeic acid phenethyl ester (CAPE) as an antidote for acute methanol (MeOH) toxicity and to compare it with ethanol. Methods: This study included five groups, each containing eight rats. The groups were control, methotrexate (MTX), MeOH, ethanol and CAPE. All rats except control group were treated with intraperitoneal (i.p.) MTX (0.3 mg/kg/d) for 7 d. At the 8th day of the experiment, i.p. injection of MeOH (3 g/kg) was administered in MeOH, ethanol and CAPE groups. Four hours after MeOH treatment, 0.5 g/kg ethanol was injected i.p. in ethanol group; 10 μmol/kg CAPE i.p. in CAPE group; serum physiologic i.p. in other groups. After 8 h, rats were anaesthetized and sacrificed. Total anti-oxidant status (TAS), total oxidant status (TOS) were measured on the dissected and excised retina and optic nerve samples. Fellow eyes were used for histopathologic evaluation and the cell count of retinal ganglion cell (RGC) layer. In addition, interactions of alcohol dehydrogenase with CAPE, ethanol, MeOH and pyrazole derivatives were investigated. Results: Either CAPE or ethanol co-treatment decreased the TOS levels and increased the TAS levels compared to the MeOH group. MeOH treatment decreased the mean cell count in RGC layer. CAPE co-treatment significantly prevented cell loss (p = 0.040). Besides, in silico calculations showed that binding affinity of CAPE to alcohol dehydrogenase was higher than those of MeOH, ethanol, and pyrazole derivatives were. Conclusion: This study demonstrated that CAPE treatment decreased the oxidative stress in acute MeOH intoxication in the retina and optic nerve; beside that, protected RGC layer histology. In silico, CAPE had higher affinity score than MeOH, ethanol, pyrazole and pyrazole derivatives in the case of interaction with alcohol dehydrogenase.

Magnesium and diltiazem relaxes phenylephrine-precontracted rat aortic rings

Perioperative vasospasm during cardiovascular surgery is a challenging problem. Several vasodilator agents are frequently utilized for its prevention in surgical practice. Magnesium and diltiazem both have known potential vasorelaxant effects. We planned to compare the efficacy of diltiazem and magnesium in relieving phenylephrine-precontracted rat aortic rings. Ten young adult female Wistar albino rats weighing 230-260 g were used in this study. The aortic rings in the organ bath equilibrated and reached their baseline tension. Precontraction was induced by 0.001 mmol/l phenylephrine and cumulative concentration-relaxation curves were obtained by consecutively increasing the addition of either diltiazem (10(-6)-0.1 mmol/l) or magnesium (0.1-10 mmol/l). The mean maximal relaxation responses observed by diltiazem and magnesium on separate aortic rings were 90 ± 3 and 53 ± 2%, respectively. The calculated EC50 of diltiazem was 0.01035 mmol/l, whereas the EC50 of magnesium was 4.064 mmol/l (P < 0.05). Both magnesium and diltiazem produced vasorelaxation on phenylephrine-precontracted rat aortic rings in this study, but the potency of diltiazem regarding the EC50 value was significantly higher than that of magnesium. Magnesium could be a candidate together with diltiazem to inhibit vasospasm on arterial grafts during coronary bypass surgery.

HISTOPATHOLOGIC EFFECTS OF GLASS IONOMER BONE CEMENTS APPLICATION TO MAXILLOFACIAL AREA: AN EXPERIMENTAL STUDY IN RABBITS

ABSTRACT Reconstruction of the maxillofacial bone defects and fractures poses a challenge to the surgeons. Various alternatives and materials have been described for these defects and fractures. Glass ionomer bone cements (GICs) have been used extensively in dentistry but recently they have also been utilized in otolaryngology. We hypothesized that GIC can be an alternative material for maxillofacial reconstruction. However, their biocompatibility is of primary importance because this material will be in direct contact with the tissue for a prolonged time and might affect it. Therefore the aim of this study was to investigate the tissue responses to GIC in the maxillofacial area in rabbits. The study was carried out on 16 New Zealand White rabbits, which were divided into study (n: 8) and control (n: 8) groups. Experimental defects and fractures were created in the nasal bone, maxilla and zygoma in both the study and the control group. The experimental fractures and defects were reconstructed by GIC in the study group. However, the rabbits in the control group were left to natural healing process. The inflammatory reaction and fibrosis in the rabbits of both the study and the control group were compared by using descriptive histopathological analysis 180 days after application. The tissue reactions were graded. GIC showed a slight inflammatory and fibrous reaction in the rabbit of the study group. Nevertheless, statistical difference between the groups was not observed in terms of inflammatory reaction and fibrosis (P>0.05). The results of this study indicated that GIC is a well tolerated material in maxillofacial reconstruction.

Impact of caffeic acid phenethyl ester treatment on vancomycin-induced pancreatic damage in rats

This study investigates the preventive effect of caffeic acid phenethyl ester (CAPE) on pancreatic damage induced by vancomycin (VCM) in rats. Rats were equally divided into three groups: group I (control), group II (only VCM-treated group) and group III (VCM + CAPE-treated groups). VCM was intraperitoneally administered at a dose of 200 mg kg−1twice daily for 7 days. CAPE was administered orally at 10 µM mL−1 kg−1 dose once daily for 7 days. The first dose of CAPE administration was performed 24 h prior to VCM injection. Blood and pancreas tissue samples were removed and collected after the study. Serum alkaline phosphatase (ALP), amylase, γ-glutamyl transferase (GGT) and lipase activities were determined. Pancreas tissue samples were evaluated with the light microscope. Group II significantly increased serum ALP, amylase, GGT and lipase activities when compared with the control group. Group III significantly decreased serum ALP, amylase, GGT and lipase activities when compared with group II. In histopathological examination, it has been observed that there was a significant pancreatic damage in group II. CAPE exerted prominent structural protection against VCM-induced pancreatic damage and this effect was statistically significant. CAPE caused a marked reduction in the extent of pancreatic damage. We have concluded that it may play an important role in the VCM-induced pancreatic damage and reduce the pancreatic damage both at the biochemical and histopathological aspects.