Borekci, Taha Berkay; Altuner, Durdu; Cicek, Betul; Bulut, Seval; Coban, Abdulkadir Taha; Suleyman, Halis

Background and Objective: Doxorubicin (DOX) use can promote neurobehavioral changes and neurodegeneration, which have been attributed to oxidative stress. Thus, this study aimed to examine the effect of Hippophae rhamnoides L., fruit extract (HRe), against possible oxidative brain damage and behavioral disorders in rats caused by DOX.Materials and Methods: A total of 24 male Sprague-Dawley rats were utilized in this study and were divided randomly into four groups (n = 6 in each groups): CG, healthy control; HRe, 50 mg/kg HRe; DOX, 5 mg/kg i.p., in a single intraperitoneal dose of DOX; Hre + DOX, 50 mg/kg HRe + 5 mg/kg DOX. HRe was administered orally once a day for two weeks, while DOX was administered intraperitoneally twice a week for two weeks. Subsequently, behavioral tests were performed-the sucrose preference test (SPT) and pole test-to assess depression-like behaviors and motor function, respectively. Then, the level of oxidative stress was biochemically evaluated in the brain tissues of the rats. One-way analysis of variance (ANOVA) was conducted, followed by a post hoc Tukey's test for the statistical analysis. A p-value < 0.05 was considered statistically significant.Results: The HRe treatment markedly reduced DOX-induced depression-like behaviors and improved motor dysfunction. The HRe treatment also restored the impaired antioxidant response by inhibiting the DOX-related malondialdehyde increase and reducing the decrease in total glutathione levels, as well as superoxide dismutase and catalase activities.Conclusion: The present study indicates that HRe treatment has beneficial effects on motor dysfunction as well as depression-like behavior associated with neurodegeneration following DOX-induced brain damage. Possible mechanisms underlying these beneficial effects include lipid peroxidation inhibition and restoration of antioxidant defense mechanisms by HRe.

Yilmaz, Betul Kalkan; Bulut, Seval; Yilmaz, Nesrin; Yucel, Nurinisa; Cicek, Betul; Kadioglu, Berrin Goktug; Bakan, Nuri; Mendil, Ali Sefa; Suleyman, Halis

Background and Objective: Rilmenidine is an antihypertensive drug with sympatholytic properties as well as antioxidative and anti-inflammatory properties. To investigate the biochemical and histopathological effects of Rilmenidine on Ovarian IschemiaReperfusion (I/R) injury in a rat model, this study aims to determine its potential protective role against oxidative stress and tissue damage associated with ovarian IR injury. Materials and Methods: The 24 albino Wistar female rats were divided into four groups: Healthy (HG), sham-operation (SOG),ovarian ischemia-reperfusion (OIRG) and Rilmenidine+ovarian ischemia-reperfusion (ROIRG). Ovaries in SOG, OIRG and ROIRG groups were exposed to ischemia for three hrs, followed by reperfusion for 6 days. The ROIRG rats were treated with Rilmenidine (0.2 mg/kg) daily for 6 days before ischemia. The ovaries were analyzed for oxidant, antioxidant and proinflammatory cytokines and examined histopathologically. Statistical analysis was performed using one-way ANOVA and Kruskal-Wallis tests (p<0.05). Results: The IR procedure increased tissue malondialdehyde, tumor necrosis factor-a, interleukin-6 and interleukin-1$ levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). Severe histopathologic damage and 8-hydroxy-20deoxyguanosine immunopositivity were also observed in ovarian tissues ofOIRG (p<0.001). Rilmenidine inhibited IR-related biochemical, histopathological and immunohistochemical abnormalities (p<0.05). Conclusion: Rilmenidine may be an efficient therapeutic strategy for the protection from ovarian IR injury.

Suleyman, Zeynep; Altuner, Durdu; Suleyman, Halis; Coban, Taha Abdulkadir; Ozkaraca, Mustafa

Background and Objective: Favipiravir is associated with more serious side effects at higher doses. This experimental study proposed to investigate the effect of favipiravir on dose-dependent lung toxicity in rats biochemically and histopathologically. Materials and Methods: The rats were divided into four groups as healthy (HG), 100 mg/kg favipiravir (FAV-100), 200 mg/kg favipiravir (FAV-200) and 400 mg/kg favipiravir (FAV-400). Favipiravir 100, 200 and 400 mg/kg doses were administered by oral gavage to the other groups except HG. To the HG group, only distilled water (0.5 mL) was applied in the same way. This procedure was repeated twice a day for a week. Then, the rats were euthanised with high-dose anaesthesia and lung tissues were removed. Oxidative stress parameters such as malondialdehyde (MDA), Total Glutathione (tGSH), superoxide dismutase (SOD), total oxidant status (TOS) and total antioxidant status (TAS) were examined. After the one-way ANOVA, the Tukey's post hoc test was performed. Results: Favipiravir dose-dependently increased MDA and TOS also decreased tGSH, SOD and TAS in rat lung tissue. As favipiravir was given in increasing doses, it was easier to observe the changes between the different groups. This was also supported by the histopathological data. Histopathologically, interstitial pneumonia and lymphoid hyperplasia were mild in the 100 mg/kg favipiravir group, severe at high doses. Conclusion: As the dose of favipiravir increased, oxidant levels increased and antioxidant levels decreased in the lung tissue. In line with these results, it was observed that favipiravir caused a dose-dependent pulmonotoxic effect in rats.

Isaoglu, Unal; Uyar, Elif Esra; Sahin, Nurullah; Bulut, Seval; Mammadov, Renad; Yilmaz, Betul Kalkan; Gunay, Murat; Mendil, Ali Sefa; Suleyman, Halis

Background and Objective: Ischemia-reperfusion (IR) causes tissue damage by inducing oxidative stress and inflammation. In this study, the protective ability of leflunomide, which is reputed to have antioxidant and anti-inflammatory effects, against IR-induced ovarian damage in rats was researched. Materials and Methods: Twenty-four albino Wistar female rats were divided into 4 groups of six each: Healthy (HG), sham-operated (SOG),ovarian IR (OIR) and leflunomide+ovarian IR (LOIR).One hour beforethe IR procedure, the LOIRgroup received 10 mg/kg leflunomide orally. Ovaries of rats in OIR and LOIR groups were subjected to 3 hrs ischaemia and 6 hrs reperfusion. For six days, leflunomide were implemented once a day. On day seven, the animals were euthanized and their ovaries were collected. The tissues were examined biochemically and histopathologically. Results: Leflunomide treatment significantly suppressed IR-induced rise in malondialdehyde (MDA),Tumor Necrosis Factor-Alpha (TNF-) and Interleukin 6 (IL-6) and the decline in Total Glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) (p<0.001). Severe stromal hemorrhage, edema and follicular hemorrhage were noted in the ovaries of the IR group. Leflunomide treatment significantly prevented IR-induced ovarian tissue damage (p<0.05). Conclusion: Leflunomide could protect the ovaries with antioxidant and anti-inflammatory activity in ovarian IR injury.

Kadioglu, Berrin Goktug; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Altuner, Durdu; Yazici, Gulce Naz; Gulaboglu, Mine; Suleyman, Halis

Background and Objective: Polymorphonuclear leukocytes (PMNLs) play an important role in the pathogenesis of oxidative ischemia-reperfusion (I/R) damage. There is information that sugammadex inhibits PMNL infiltration into organs and tissues undergoing I/R. Present study aimed to investigate the potential protective effect of sugammadex against I/R-induced ovarian damage in rats and to elucidate its mechanism of action. Materials and Methods: The 24 female albino Wistar-type rats were divided into four groups as follows: Sham operation (SG), ovarian I/R (IRG), sugammadex (4 mg/kg) +ovarian I/R (SIR-4) and sugammadex (8 mg/kg) +ovarian I/R (SIR-8). Sugammadex was administered intraperitoneally. The animals were subjected to 2 hrs of ischemia followed by 2 hrs of reperfusion. Results: Sugammadex significantly inhibited the increase in I/R-induced malondialdehyde and the decrease in total glutathione, superoxide dismutase and catalase levels in ovarian tissue at a dose of 8 mg/kg compared with the dose of 4 mg/kg. Moderate follicular degeneration, vascular congestion, necrosis, oedema and hemorrhage were observed in the sugammadex (4 mg/kg) group, which significantly reduced the increase in I/R-related PMNL infiltration in ovarian tissue. Only mild vascular congestion was observed in the ovarian tissue of the 8 mg/kg sugammadex group, which did not show PMNL infiltration. Conclusion: Histopathological findings show that sugammadex protects ovarian tissue from oxidative and inflammatory injury of the I/R by inhibiting PMNL infiltration. Results also suggest that an 8 mg/kg dose of sugammadex, which completely inhibits PMNL infiltration into ovarian tissue, may be more beneficial than the 4 mg/kg dose in the treatment of I/R-induced ovarian damage.

Demir, Omer Faruk; Suleyman, Zeynep; Suleyman, Halis; Coban, Taha Abdulkadir; Mokhtare, Behzad

Background and Objective: Everolimus is an anticancer agent that inhibits the Mammalian Target of Rapamycin (mTOR). It causes side effect such as pneumonia. This study aimed to evaluate rutin's effect on potential pulmonary injury in everolimus-administered rats biochemically and histopathologically. Materials and Methods: All rats were split into: Healthy (HG), everolimus-treated (EVR) (2 mg/kg) and rutin (50 mg/kg)+everolimus-treated (REV). Rutin was administered to the REV group and physiological saline was given orally tothe EVR and HG groups. As 1 hr later, everolimus 2 mg/kg was administered to REV and EVR groups. The process was repeated daily, 4 times weekly. Then, high dose anaesthesia was used to kill the rats and lung tissue samples were extracted. Oxidative stress and pro-inflammatory cytokine markers were examined and ANOVA test was applied. Results: Oxidative and inflammatory lung damage developed in the everolimus-treated rats. Rutin attenuated this oxidative and pro-inflammatory lung damage induced by everolimus. Rats administered with everolimus developed severe interstitial pneumonia, lymphoid hyperplasia and desquamation in lung tissues. This severe damage was reduced to mild level by administering rutin. Conclusion: The adding rutin to the treatment regimen for pulmonary damage associated with everolimus may have a preventive impact.

Unver, Edhem; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis

Background and Objective: Acrolein-induced tissue damage has been attributed to oxidative stress and inflammation.This study aimed to determine the effects of adenosine triphosphate (ATP) and agomelatine, two substances known to have antioxidant and antiinflammatory effects, separately and in combination, on possible acrolein-induced lung damage in rats. Materials and Methods: There were 30 albino Wistar rats divided into five groups of six: Healthy (HG), acrolein (AC), ATP+acrolein (ATAC), agomelatine+acrolein (AGAC) and ATP+agomelatine+acrolein (AAAC). The dose of ATP administered intraperitoneally was 4 mg/kg and the dose of agomelatine administered orally was 25 mg/kg. An oral dose of acrolein 3 mg/kg was given 1 hr following the administration of ATP and agomelatine. For 30 days, the treatment protocol was followed once a day. Afterwards, the rats were euthanized and their lungs were removed. Oxidants, antioxidants and pro-inflammatory cytokines were measured in lung tissues. Results: In lung tissues, acrolein increased malondialdehyde, nuclear factor kappa, tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 levels and decreased total glutathione, superoxide dismutase and catalase levels (p<0.001). The ATP+agomelatine, ATP and agomelatine treatments were the most effective at preventing these biochemical changes, respectively (p<0.001). As a result, the biochemical data of the HG and AAAC groups were similar (p>0.05). Conclusion: It could be suggested that both ATP and agomelatine might be effective against the pneumotoxic effects of acrolein, though a combination therapy would be more effective.

Yasar, Hasan; Cimen, Ferda Keskin; Suleyman, Halis; Kurt, Nezahat; Arslan, Yusuf Kemal

Background and Objective: Cisplatin is a drug used to treat cancer, but it causes oxidative damage to muscle tissue. Rutin has an antioxidant effect. The study aims to investigate the biochemical and histopathological effects of rutin on the oxidative damage of cisplatin in skeletal muscle tissue. Materials and Methods: Rats were divided into four groups: A control group (CG), an only cisplatin-administered group (CIS), a cisplatin and rutin 50 mg kg(-1)-administered group (R-50) and a cisplatin and rutin 100 mg kg(-1)-administered group (R-100). Analyses were performed from the hindlimb muscles of experimental animals. Analyses of malondialdehyde (MDA), Total Glutathione (tGSH), glutathione reductase (GSHRd), glutathione S-transferase (GST) and superoxide dismutase (SOD) were performed. Histopathologic examination was performed in all groups. The CG and the other groups were compared. Results: The CG and R-100 groups were similar in all biochemical examinations. A statistically significant difference was detected between the control group and the CIS and R-50 groups in all examinations. Histopathological examinations revealed oxidative damage of cisplatin in the CIS group and R-50 group. The findings in the R-100 group were similar to the control group. Conclusion: Cisplatin causes oxidative damage to skeletal muscle tissue. Rutin has the potential to prevent the formation of such oxidative damage.

Dinc, Kemal; Kiremitli, Tunay; Kiremitli, Sevil; Ozyurt, Ramazan; Bulut, Berk; Bulut, Seval; Yavuzer, Bulent; Suleyman, Halis; Aggul, Ahmet Gokhan; Mokhtare, Behzad

Bedir, Zehra; Erdem, Kezban Tuna Ozkaloglu; Can, Abdullah; Cicek, Betul; Gulaboglu, Mine; Suleyman, Zeynep; Gursul, Cebrail; Mokhtare, Behzad; Ozcicek, Fatih; Suleyman, Halis

Background and Objective: Metamizole is a non-selective cyclooxygenase (COX) inhibitor NSAID with a strong analgesic and spasmolytic effects. It is the most common analgesic in the world. Thiamine pyrophosphate (TPP) protects the liver tissue against oxidative damage. The aim of our study was to analyze the effect of TPP against possible liver injury and dysfunction of metamizole in rats biochemically and histopathologically. Materials and Methods: The animals were grouped as healthy (HG), 500 mg kg(-1) metamizole (MT-500), 1000 mg kgG1 metamizole (MT-1000), 25 mg kg(-1) TPP+500 mg kg(-1) metamizole (TMT-500), 25 mg kg(-1) TPP+1000 mg kg(-1) metamizole (TMT-1000) groups. The TMT-500 and TMT-1000 groups of animals were injected intraperitoneally (ip) at the dose of 25 mg kg(-1) of TPP. Distilled water as the solvent was injected ip to the HG, MT-500 and MT-100 groups. One hour after injecting TPP and distilled water, metamizole 500 and 1000 mg kg(-1) doses were administered orally to the TMT-500 and TMT-1000 groups. The TPP was administered once and metamizole twice a day for 14 days. The animals were euthanized with high-dose anesthesia. The liver tissues excised from the animals were analyzed biochemically and histopathologically. Results: In both doses metamizole significantly increased MDA, ALT and AST levels and decreased tGSH, SOD and CAT levels compared to the healthy group. TPP significantly prevented the decrease of tGSH, SOD and CAT levels and the increase of MDA, ALT and AST levels with metamizole. There was no statistical difference in all of the levels between the TMT-500 and TMT-1000 groups. The histopathological findings indicated TPP significantly suppressed the damage induced by metamizole. Conclusion: The metamizole was possible to cause moderate damage to liver tissue. Therefore, it was considered that the use of TTP to reduce liver toxicity could be clinically beneficial.