Emir, Izzet; Suleyman, Zeynep; Suleyman, Halis

It is known that a sudden increase in cerebral blood flow (hyperper-fusion) with carotid revascularisation may disrupt and damage the blood-brain barrier. This study aimed to explore thiamine pyrophosphate’s (TPP) protective effects against potential brain and heart damage resulting from carotid cross-clamping and unclamping in rats. The animals were divided into common carotid cross-clamping and unclamping (CCU), TPP+common carotid cross-clamping and unclamping (TCCU), and sham operation (SG) groups. The TCCU group received an intraperitoneal injection (IP) of 20 mg/kg TPP one hour before anesthesia. The CCU and SG groups received distilled water as a solvent. Ischemia was induced by maintaining the clips closed for 10 min. For the SG group, only a subcutaneous incision was made. Afterward, the clips were removed, the incisions were stitched, and reperfusion was continued for six hours. Subsequently, the rats were euthanized with high-dosage general anesthesia, and heart and brain tissues were removed. TPP significantly suppressed the I/R-induced malondialdehyde (MDA) increase and decreased total glutathione (tGSH) levels in brain and heart tissues. TPP prevented the increase of tumor necrosis factor-alpha (TNF-α), interleukin-1 β (IL-1β), and interleukin-6 (IL-6) levels in both brain and heart tissues. In blood serum, TPP suppressed I/R-induced increase in troponin I (TP I) and creatine kinase-MB (CK-MB) in the blood. TPP was shown to protect the brain and distant cardiac tissues against oxidative and inflammatory damage induced by cerebral I/R.

Elma, Bekir; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Unver, Edhem; Altuner, Durdu; Coban, Taha A.; Mokhtare, Behzad; Suleyman, Halis

Favipiravir is a broad-spectrum antiviral drug that is a viral RNA-dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidipine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Laci-dipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathi-one), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopatho-logically examined. The systemic administration of high doses of favipiravir in-creased oxidant levels and decreased antioxidant levels in the lung tissue of rats. In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mit-igating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine administration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against favipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.

Yeter, Bahtınur; Mammadov, Renad; Koc, Zeynep; Bulut, Seval; Tastan, Tugba Bal; Gulaboglu, Mine; Suleyman, Halis

Isoniazid and rifampicin (IRC) have been shown to cause hepatotoxicity in both clinical and preclinical studies. Oxidative stress and inflammation have been held responsible for the pathogenesis of IRC-induced hepatotoxicity. Antioxidative and anti-inflammatory effects of thiamine pyrophosphate (TPP) and cinnamon extract (CE) have been shown in previous studies. Therefore, our study investigated the protective effects of TPP and CE on possible liver damage caused by IRC treatment in rats. Twenty-four albino Wistar rats were categorized into four groups: a healthy group (HG), an IRC group (IRG), a TPP+IRC group (TIRG), and a CE+IRC group (CIRG). TPP (25 mg/kg) was administered intraperitoneally to TIRG, while CE (100 mg/kg) was administered orally to CIRG. In IRG, TIRG, and CIRG, isoniazid (50 mg/ kg) and rifampicin (50 mg/kg) were administered orally one hour after these treatments. For seven days, this procedure was repeated once a day. After this period, blood samples were taken from the tail veins, and the rats were sacrificed. The removed liver tissues were analyzed for oxidant, antioxidant, and proinflammatory cytokines and subjected to histopathological evaluation. Serum alanine aminotransferase and aspartate aminotransferase activities were also measured. An increase in malondialdehyde, nuclear factor kappa B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6 levels, a decrease in total glutathione levels, superoxide dismutase and catalase activities, and an increase in alanine aminotransferase and aspartate aminotransferase activities were found with IRC treatment (p<0.001). The histopathological analysis of the IRG suggested hepatotoxicity (p<0.001). TPP and CE administered with IRC inhibited the biochemical changes (p<0.001). In the TIRG, this inhibition was higher than in the CIRG (p<0.05). Histological damage was inhibited by TPP (p<0.001). CE prevented biochemical changes but not histological changes except inflammatory cell infiltration. Therefore, TPP may be better than CE in preventing IRC-induced hepatotoxicity.

Bicer, Senol; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Cicek, Betul; Altuner, Durdu; Coban, Taha A.; Suleyman, Halis

Several studies have reported that oxidative stress, and proinflam-matory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and interleukin-six (IL-6) are the main factors underlying bladder ischemia-reperfusion (I/R) damage. Anakinra and tocilizumab are known to be antioxidants and proinflammatory cytokine inhibitors. Our study aims to investigate if anakinra, tocilizumab, and the combination (ATC) thereof have a protective effect against oxidative and inflammatory bladder damage induced through the I/R procedure in rats, and evaluate by comparing these compounds. Male rats were divided into five groups: bladder sham-operation applied group (SG); bladder only I/R applied group (IRG); anakinra+bladder I/R applied group (AIR); tocilizumab+bladder I/R applied group (TIR); and ATC+bladder I/R applied group (ATIR). An atraumatic clamp was placed on the abdominal aorta of animals in all groups (except SG), and one hour of ischemia followed by two hours of reperfusion was performed. Our biochemical find-ings showed that anakinra and tocilizumab significantly inhibited the increase of oxidant malondialdehyde (MDA) and the decrease of antioxidants such as total glu-tathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in bladder tissue by I/R, both at the same levels. Furthermore, anakinra and tocilizumab significantly suppressed the I/R-associated increase of TNF-α, IL-1β, and IL-6 in bladder tissue. ATC was the one that best prevented the I/R-related increase in MDA, TNF-α, IL-1β, and IL-6 and the decrease in tGSH, SOD, and CAT in the bladder tissue. ATC was more beneficial than anakinra or tocilizumab alone in treating bladder I/R damage.

Aynaoglu Yildiz, Gulsah; Yapca, Omer Erkan; Dinc, Kemal; Gursul, Cebrail; Gundogdu, Betul; Aktas, Mehmet; Suleyman, Zeynep; Bulut, Seval; Suleyman, Halis

Many types of stress, including psychological stress, negatively affect reproductive health. This study aimed to investigate the effects of sertraline (a selective serotonin reuptake inhibitor), cerebrolysin (neuroprotective/neurotrophic), and a combination of both against stress-induced ovarian damage, infertility and pregnancy delay in female rats. The rats were divided into five groups (n=14/each group) as healthy (HG), stress control (StC), stress+sertraline (SS), stress+cerebrolysin (SC), and stress+sertraline+cerebrolysin (SSC). To induce stress, animals (except the HG) were kept in a supine position with their forelimbs and hindlimbs (FIM) tied for one hour. Then, sertraline (20mg/kg) was given orally to the SS. Cerebrolysin (2.5ml/kg) was injected into the SC subcutaneously. Sertraline+cerebrolysin was administered to SSC with the same methods and doses. FIM and drug administration continued for 30 days. Six rats from each group were euthanized with high-dose anesthesia, right and left ovarian tissues were removed, and tissues were examined biochemically and histopathologically. The remaining rats were taken for breeding. Exposure to stress in rats caused an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels and a decrease in total glutathione (tGSH). Stress was related to histopathological damage, infertility, and delayed birth. The sertraline and cerebrolysin combination was the most effective in preventing these changes, with sertraline and cerebrolysin alone in second and third places, respectively. Regarding efficacy, selective serotonin reuptake inhibitors (SSRIs) and related drugs may be beneficial in treating stress-related ovarian damage, infertility, and delay in pregnancy.