Synergistic effects of ozone with doxorubicin on the proliferation, apoptosis and metastatic profile of luminal-B type human breast cancer cell line.

OBJECTIVE: Luminal-B type human breast cancer cell line (BT-474) to assess the synergistic effects of ozone applied after chemotherapeutic treatment with various dosages of doxorubicin, and compare the results with the effects on L929 fibroblast cell line. METHODS: Doxorubicin (1-50 M) was added to each cell lines and left to sit for 24 h at 37 °C. Then, as combination groups, half of the groups were incubated with 30 g/mL ozone for 25 min. Tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), and matrix metalloproteinase-2 and - 9 (MMP-2 and MMP-9) levels were measured using the MTT test, flow cytometry, and immunocytochemistry, respectively. RESULTS: When compared to simply doxorubicin-applied cells without ozone treatment, each dose of doxorubicin + ozone treatment considerably boosted L929 viability but significantly decreased BT-474 viability. Additionally, the combination increased the apoptotic impact of doxorubicin on BT-474 but not L929 (P < 0.001). TGF-, MMP-2, and MMP-9 levels of L929 after combination were substantially higher than those of the other groups (P < 0.01). Doxorubicin's effect on BT-474's protein levels, which had significantly decreased in comparison to those of the other groups, was reversed by the combination treatment (P < 0.05). CONCLUSION: Doxorubicin's anti-proliferative and apoptotic effects were enhanced by ozone treatment in BT-474 cells, but it also repaired and healed healthy fibroblast cells that had been harmed by the cytotoxicity of the chemotherapy drug. If doxorubicin and ozone treatment are coupled, BT-474 cells may develop resistance to it through expressions of TNF-α, TGF-ß, MMP-2, and MMP-9.

Ozone combined with doxorubicin exerts cytotoxic and anticancer effects on Luminal-A subtype human breast cancer cell line.

OBJECTIVE: We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line. METHODS: Both cell lines were incubated with increasing doses of doxorubicin (1-50 µM) for 24 h at 37°C. Then, half of groups were incubated with 30 µg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry. RESULTS: Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively). CONCLUSION: Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.

Evaluation of the appendectomy cases performed under emergency conditions during the COVID-19 pandemic and discussed with the pathology reports.

BACKGROUND: The aim of this study is to examine the cases underwent appendectomy during the COVID-19 pandemic and to discuss the pathology reports of patients. METHODS: During the COVID-19 pandemic, the pathological reports of the appendectomy materials of 588 patients over the age of 15 who applied to the emergency department between January 1, 2020, and June 1, 2021, were examined. A total of 565 patients with a diagnosis of acute (AA), subacute (SA), or perforated appendicitis (PA) were included and divided into three groups according to diagnosis. Twenty-three patients were excluded from the study due to other pathologies. The age, gender, duration of pain, ASA score, operational technique, operation time, Clavien-Dindo score, hospitalization time, post-operative complications, pre- and post-operative PCR and thoracic tomography findings in suspected cases of COVID-19, and laboratory and radiological findings of patients were retrospectively analyzed. RESULTS: Of 565 patients diagnosed with appendicitis, 464 (82.1%) had AA, 35 (6.2%) SA, and 66 (11.7%) PA. The median age of the PA group was higher than in the AA group (p=0.0139). The incidence of diabetes mellitus in the PA group and of asthma in the SA group were highest among other groups (p=0.004 and 0.0037, respectively). The duration of pain was longer in the SA and PA groups than the AA group (p<0.0001), therefore, the patients applied to hospital later than the acute group. The rate of thorax CT-positive scans was 1.6% in patients suspected for COVID-19 (p=0.066). While laparoscopic surgery was preferred over 70% in all groups, the rate of conventional surgery (21.1%) in the AA group was highest and of transition from laparoscopic to open surgery was highest in the PA group (10.6%) (p<0.0001). Hospitalization duration was longest in the PA group (p<0.0001). CONCLUSION: COVID-19 pandemic not only changes all routines of social life but also complicates the treatment and manage-ment of cases with AA symptoms applied to hospital under emergency conditions. Follow-up of the appendectomy specimen is crucial in terms of excluding other pathologies.

Ozone combined with doxorubicin exerts cytotoxic and anticancer effects on Luminal-A subtype human breast cancer cell line

SUMMARY OBJECTIVE: We aimed to examine the potential anticancer effects of ozone applied after chemotherapeutic treatment with different concentrations of doxorubicin in Luminal-A subtype of human breast cancer cell line (MCF-7) and compare the results with effects on L929 fibroblast cell line. METHODS: Both cell lines were incubated with increasing doses of doxorubicin (1-50 μM) for 24 h at 37°C. Then, half of groups were incubated with 30 μg/mL ozone for 25 min as combination groups. Cell viability was analyzed by MTT assay, apoptosis by flow cytometry, and levels of tumor necrosis factor alpha, transforming growth factor beta, and matrix metalloproteinase-2 and MMP-9 by immunocytochemistry. RESULTS: Doxorubicin + ozone treatment enhanced viability of L929 (p<0.01) but reduced viability of MCF-7 compared to only doxorubicin-applied cells without ozone treatment (p<0.001). This combined treatment also enhanced apoptotic effect of doxorubicin on MCF-cells (p<0.001), but not on L929. It significantly increased all protein levels of L929 compared with those of other groups (p<0.05 for tumor necrosis factor alpha and MMP-2; p<0.01 for transforming growth factor beta and MMP-9). This treatment reversed the effect of doxorubicin on tumor necrosis factor alpha levels and considerably reduced MMP-2 and MMP-9 levels of MCF-7 compared with those of control group (p<0.01 and p<0.001, respectively). CONCLUSION: Ozone treatment potentiated the apoptotic and anticancer activities of doxorubicin in MCF-7 cells and showed repairing and healing effect on healthy fibroblast cells, which were damaged from cytotoxic effects of chemotherapeutic agent. MCF-7 cells may acquire sensitivity against the doxorubicin combined with ozone treatment through activating tumor necrosis factor alpha, MMP-2, and MMP-9 expressions.

The effects of onlay titanium-coated mesh on recurrence, foreign body sensation and chronic pain after ventral hernia repair.

BACKGROUND/OBJECTIVE: There are many complications of meshes in hernia repair. The aim of this study was to investigate the effects of onlay titanium-coated meshes (TCM) on recurrence, foreign body sensation and chronic pain in ventral hernia repair. METHODS: In this retrospective study, 160 patients undergone TCM or polypropylene mesh (PM) surgery for onlay repair of ventral hernia were examined between May 2014 and January 2018 at our center. Patient characteristics, type of hernia, defect size, operative time, follow-up time, surgical site occurrence (infection, seroma and hematoma), recurrence, foreign body sensation and chronic pain were analyzed. Patients were divided into two groups according to mesh used: TCM (titanium group) or PM (polypropylene group). RESULTS: Out of 160 patients, 63 (32.6%) had TCM and 97 (67.4%) had PM. There was no significant difference between groups in terms of recurrence (p = 0.757). Chronic pain and foreign body sensation were low in the titanium group (p = 0.047 and p = 0.029, respectively), a positive correlation was found between surgical site infection and recurrence (p = 0.020). In the polypropylene group, an increase in defect size was significantly associated with foreign body sensation and chronic pain (p < 0.001 for both comparisons). CONCLUSION: In onlay repair of ventral hernia, TCM led to less foreign body sensation and chronic pain then PM. The surgical site infection was associated with recurrence for these meshes. Additionally, the increase in defect size causes a risk for foreign body sensation and chronic pain in repair using PM.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects.

PURPOSE: To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. METHODS: Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. RESULTS: Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). CONCLUSIONS: The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity.

Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P <  0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P <  0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

A comparison of the quantitative evaluation of in situ parathyroid gland perfusion by indocyanine green fluorescence angiography and by visual examination in thyroid surgery

ABSTRACT Objective The most vital complications of thyroidectomy are recurrent nerve damage and hypocalcaemia. We aimed to compare the tissue perfusion scores (PS) of IG fluorescence angiography (IGFA) and visual examination by the surgeon after total thyroidectomy. Subjects and methods Forty-three patients were accepted into the study. Localisation of the parathyroid gland (PG) was determined by the naked eye and scored in terms of tissue perfusion. The averages of fluorescent light intensities for each IGFA were calculated, the perfusions were scored and compared with the PS given by the surgeon. Biochemical parameters were noted. Results 37.2% of patients had autotransplanted PGs, according to their visual scores. The means of IGFA-PS for PGs scored as 0, 1 or 2 on visual inspection were 48.58 ± 4.49 [30-70], 89.65 ± 8.93 [36-144] and 158.76 ± 8.93 [70-253], respectively, which correlated with the visual PSs in a statistically significant manner (P < 0.0001). The predictive cut-off value for IGFA-PS was determined to be 70, given a visual PS of 0 (95% CI [0.72-0.85]), and this was interpreted to be a candidate cut-off point for the autotransplantation of PGs. Conclusion IGFA scoring may be considered as an operative predictor, providing objective criteria to evaluate the tissue and blood perfusion of PGs after thyroidectomy. IGFA scoring may be considered to have value in minimising postoperative permanent hypoparathyroidism in patients.

A comparison of the quantitative evaluation of in situ parathyroid gland perfusion by indocyanine green fluorescence angiography and by visual examination in thyroid surgery.

Objective The most vital complications of thyroidectomy are recurrent nerve damage and hypocalcaemia. We aimed to compare the tissue perfusion scores (PS) of IG fluorescence angiography (IGFA) and visual examination by the surgeon after total thyroidectomy. Subjects and methods Forty-three patients were accepted into the study. Localisation of the parathyroid gland (PG) was determined by the naked eye and scored in terms of tissue perfusion. The averages of fluorescent light intensities for each IGFA were calculated, the perfusions were scored and compared with the PS given by the surgeon. Biochemical parameters were noted. Results 37.2% of patients had autotransplanted PGs, according to their visual scores. The means of IGFA-PS for PGs scored as 0, 1 or 2 on visual inspection were 48.58 ± 4.49 [30-70], 89.65 ± 8.93 [36-144] and 158.76 ± 8.93 [70-253], respectively, which correlated with the visual PSs in a statistically significant manner (P < 0.0001). The predictive cut-off value for IGFA-PS was determined to be 70, given a visual PS of 0 (95% CI [0.72-0.85]), and this was interpreted to be a candidate cut-off point for the autotransplantation of PGs. Conclusion IGFA scoring may be considered as an operative predictor, providing objective criteria to evaluate the tissue and blood perfusion of PGs after thyroidectomy. IGFA scoring may be considered to have value in minimising postoperative permanent hypoparathyroidism in patients.

Potent therapeutic effects of ruscogenin on gastric ulcer established by acetic acid.

BACKGROUND/OBJECTIVE: The present study investigated the potent therapeutic effects of Ruscogenin, main steroid sapogenin of traditional Chinese plant called 'Ophiopogon japonicas', on chronic ulcer model established with acetic acid in rats. METHODS: 24 rats were attenuated to the sham (2 ml/kg/day isotonic solution), control (untreated ulcer) and treatment (3 ml/kg/day ruscogenin) groups. After treatment for 2 weeks, gastric tissues were collected and prepared for light microscopic (H&E), immunohistochemical (Collagen I, III and IV) and biochemical analysis [Epidermal growth factor (EGF), Prostaglandin E2 (PGE2), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 and 8 (IL-6 and IL-8), Lipid Peroxidase (LPO), Myeloperoxidase (MPO), Glutathione (GSH) and Glutathione Peroxidase (GSH-Px)] and transmission electron microscopy (TEM). RESULTS: Macroscopic scoring showed that the ulceration area of ruscogenin-treated group decreased compared with control group. Immunohistochemical analysis revealed ruscogenin ameliorated and restored the levels of Collagen I and IV to the levels of sham group. Tissue levels of EGF and PGE2 enhanced significantly in untreated ulcer group while were higher in treated ulcer group than the control group. TNF-α, IL-6, IL-8, LPO, MPO levels increased significantly in control group whereas decreased in treated rats after ruscogenin treatment. However, levels of GSH and GSH-Px increased significantly in treatment group. TEM showed chief cells and parietal cells of ulcer group having degenerated organelles while ruscogenin group had normal ultrastructure of cells. CONCLUSION: There are potent anti-inflammatory and anti-oxidant effects of ruscogenin on gastric ulcer and may be successfully used as a safe and therapeutic agent in treatment of peptic ulcer.

Examination of protective and therapeutic effects of ruscogenin on cerulein-induced experimental acute pancreatitis in rats.

PURPOSE: To determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats. METHODS: Overall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1ß [IL-6 and IL-1ß], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy. RESULTS: The protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1ß, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group. CONCLUSION: The present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease.

Psychological well-being and marital satisfaction in response to weight loss after bariatric surgery.

PURPOSE: To compare the marital satisfaction (MS) and psychological well-being (PWB) of men and women before and after bariatric surgery for obesity. METHODS: The subjects of this prospective observational study were obese patients who underwent bariatric surgery. MS and PWB were assessed before, and 6 months after the surgery, using specific scales for MS and PWB. RESULTS: The correlation matrix showed that age was not correlated with any of the scores from the PWB scales, and only with the total MS scores of men (P < 0.05). The pre-surgical BMI-post-surgical BMI (ΔBMI) was correlated negatively and significantly with the post-surgical total MS, especially for women, but it was not correlated with the sexual satisfaction of either gender. The score of positive interpersonal relationships was negatively correlated with the ΔBMI, especially for women (P < 0.05), whereas personal improvement was positively correlated for men (P < 0.05). There was also a significant correlation between ΔBMI and purpose in life for both genders. Post-surgical ΔBMIs were not associated with the other two indicators of PWB, namely, autonomy and environmental mastery for both genders. CONCLUSIONS: For women, weight loss after bariatric surgery seemed to improve PWB and MS when assessed 6 months post-operatively; however, the psychiatric assessment of patients before and after the surgery is crucial.

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats.

PURPOSE: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). METHODS: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. RESULTS: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1ß, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. CONCLUSION: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.

Evaluation of prophylactic and therapeutic effects of ruscogenin on acute radiation proctitis: an experimental rat model.

PURPOSE: Radiation proctitis (RP) is inflammation and damage to the rectum, manifested secondary to ionizing radiation utilized for treatment. In this study, we evaluated the anti-inflammatory therapeutical and protective effects of ruscogenin in a model of acute RP. METHODS: Thirty-two Sprague-Dawley rats were divided into 4 groups (n = 8) as sham, control, treatment, and prophylaxis groups. Prophylaxis group and treatment group were dosed ruscogenin by oral gavage for 14 days pre- and postradiation. At the end of the 28th day, all subjects were sacrificed. RESULTS: Histopathological analysis showed a significant increase in cryptitis abscess, cryptitis and reactive atypia, and depth of lymphocytic infiltration of the control group, compared to the other groups (P < 0.05), while treatment and prophylaxis groups showed significant decreases (P < 0.05). Immunohistochemical analysis indicated that immunoreactivity were significantly higher in control group (P < 0.05, P < 0.001, and P < 0.01, respectively), but vice versa for treatment and prophylaxis groups. There was not any significant difference for fibroblast growth factor 2 immunoreactivity. The epithelium of control rectums indicated an increase in TNF-α immunoreactivity while other groups had significant decrease (P < 0.01). Electron microscopical findings were parallel to light microscopy. CONCLUSION: In this study, ruscogenin was observed to be effective on prophylaxis or treatment of acute RP. Although there are various reports on the treatment of the rectum damaged by acute RP in the literature, this could be the first study since there is no research indicating the ultrastructural effect of ruscogenin.

Evaluation of prophylactic and therapeutic effects of sildenafil on acute radiation proctitis in rats

Abstract Purpose: To investigate the prophylactic and therapeutical effects of sildenafil in a model of acute radiation proctitis (ARP). Methods: All experimental procedures of this study was examined by histopathological, immunohistochemical and transmission electron microscopic analysis. Results: Our histopathological evaluations indicated significant increases in lesion severity, cryptic apsis, cryptitis, cryptic distortion, reactive atypia and infiltration depth of the control (proctitis) group. While the prophylaxis group and the treatment group had significantly lower scores. High-dose group showed similar results as prophylaxis group. Histopathological findings of the prophylaxis group was more significant than the treatment group. Immunoreactivities of IL-1β, FGF-2, TNF- α and HIF-1α increased in the control group especially in the epithelial and cryptic regions. On the contrary, sildenafil application caused significant decreases of inflammatory markers in all treatment groups, specifically better results in the prophylaxis group. Conclusion: The sildenafil has anti-inflammatory effects on ARP, as well as protective effects against ARP and the protective effect of sildenafil surpasses its therapeutic effect histopathologically.