Bunyamin Unal

Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study

Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)‐induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD‐treated CLP group; (ii) 20 mg/kg SLD‐treated CLP group; (iii) CLP group; and (iv) sham‐operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil‐treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham‐operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)‐α level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP‐induced sepsis via maintenance of the oxidant–anti‐oxidant status and decrease in the level of TNF‐α.

Effects of diabetes and ovariectomy on rat hippocampus (A biochemical and stereological study)

Oxidative stress is one of the main reasons of both menopause and diabetes. So, it plays crucial role in the pathogeneses of that condition and disease. Therefore, the objective of the present study was to investigate the effects of menopause and diabetes upon the hippocampus using a rat model. Adult female Sprague Dawley rats (n = 24) were allocated randomly as follows; control (C group) ovariectomized (O group), diabetic (D group) and ovariectomy plus diabetic groups (DO group) (n = 6; in each group), respectively. For evaluating the results, tissue biochemistry and stereological analysis were made. Biochemistry results (lipid peroxidase (LPO); catalase (CAT); superoxide dismutase (SOD); total glutatyon (GSH); and myeloperoxidase (MPO) values) in Group C-DO were determined as 12.27, 21.88, 23.08 and 29.90 nmol/gr tissue; 59.3, 70.06, 69.7 and 78.1 mmol/min/mg tissue; 174.2, 156.4, 159.7 and 154.6 mmol/min/mg tissue; 3.63, 3.61, 4.21 and 3.97 nmol/mg tissue; and 5.05, 5.68, 5.58 and 6.19 µmol/min/mg tissue, respectively. Moreover, both menopause and diabetes led to change of lipid profiles. There were significant differences between the control and other groups (Group C and D-DO) (p < 0.01) and among experimental groups (p < 0.01) in terms of neuron number. When the volumes of the hippocampus were compared, there were no significant differences between the all groups (P > 0.05). At this point, we suggested that diabetes could aggravate deleterious effects of ovariectomy.

Relationship between Oxidative Stress and Cardiomyopathic Changes in Ovariectomized Rats

Objectives: Menopause has a negative effect on cardiovascular functions. However, very little is known of the overall effect of menopause on the cardiac ultrastructure or the pathophysiological basis of this. Methods: A group of 12-week-old female Sprague Dawley rats were randomly allocated to healthy control (n = 6) and ovariectomy groups (n = 6). Twelve weeks after ovariectomy, the rats’ cardiac tissues were histopathologically analyzed for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of glutathione (GSH) and lipid peroxidation (LPO)]. Results: When compared to the control group, the ovariectomy group showed cardiomyopathic changes. In tissue, activities of CAT (185 ± 2.4 vs. 112 ± 1.4 mmol/min/mg tissue; p < 0.05), SOD (153 ± 1.0 vs. 146 ± 0.7 mmol/min/mg tissue; p < 0.05) and MPO (19 ± 0.8 vs. 8.6 ± 0.11 µmol/min/mg tissue; p < 0.05) and LPO levels (32.1 ± 0.77 vs. 14.4 ± 0.20 nmol/g tissue; p < 0.05) were significantly increased in the ovariectomy group when compared to the control group. However, GSH levels (3.43 ± 0.02 vs. 3.73 ± 0.01 nmol/g tissue; p < 0.05) were significantly lower in the ovariectomy group when compared to the control group. Conclusion: Using an experimental animal model, we were able to demonstrate that menopause causes cardiomyopathic changes, and we propose that these changes could be mediated by oxidative stress.

Stereological and histological analysis of the developing rat heart.

With 9 figures and 1 table

Evaluation of patients with multiple sclerosis using a combination of morphometrical features and clinical scores

Our aim was to measure cerebellum volume (CV), sclerotic plaque numbers (PN), and plaque surface area (SA) in the parietal lobe, and to investigate the relationship between CV and PN or SA in the parietal lobe, and the clinical status of patients with multiple sclerosis (MS). MRIs were performed in 14 patients with relapsing-remitting MS (RRMS), 13 patients with secondary progressive MS (SPMS), and 26 healthy control participants. The Cavalieri method was used to measure CV and SA. The cerebellum volume was significantly reduced in MS patients compared to controls (p < 0.01). In all patients, CV was negatively correlated with the duration of the disease, relapse number, and Expanded Disability Status Scale (EDSS) scores (p < 0.01). CV was related to mean PN in both the right and left parietal lobes (p < 0.01) and mean SA (p < 0.05) in RRMS patients; CV was also correlated with mean PN (p < 0.01) and mean SA (p < 0.05) in SPMS patients. The progression index (Pi) values were 2.03 +/- 0.4 in RRMS patients and 0.83 +/- 0.2 in SPMS patients (p = 0.023, t = 2.612) (where Pi = EDSS/time from onset in years). We propose that atrophy begins both in the supratentorial and infratentorial areas simultaneously in the RR stage, and that the Cavalieri method can be used to predict SPMS among patients with RRMS.