Yaşar Şahin

Gentamicin (GTC) is a widely used aminoglycoside antibiotic, but its therapeutic application is limited by nephrotoxic and hepatotoxic effects primarily driven by oxidative stress. This study investigated the potential protective role of cranberry (CRB) (Vaccinium macrocarpon), known for its antioxidant and anti-inflammatory properties, against GTC-induced nephrotoxicity in rats. Hepatic biochemical and histopathological parameters were also evaluated as supportive markers of systemic toxicity. Thirty-two rats were divided into four groups: Control, CRB, GTC + CRB, and GTC. GTC (80 mg/kg, s.c.) and CRB (200 mg/kg, p.o.) were administered for seven consecutive days. Biochemical analyses showed significant increases in serum BUN, urea, creatinine, ALT, and AST levels in the GTC group, confirming renal and hepatic impairment. Co-treatment with CRB reduced these elevations and improved antioxidant parameters, reflected by decreased MDA and oxidative stress index levels and increased total and native thiols (p < 0.001). Gene expression analyses demonstrated that GTC upregulated pro-apoptotic genes (Bax, caspase-3, -9) and downregulated the anti-apoptotic Bcl-2, whereas CRB co-administration reversed these alterations. Histopathological evaluations supported the biochemical findings, revealing severe tubular and hepatocellular necrosis, inflammatory infiltration, and hemorrhage in the GTC group, which were markedly alleviated by CRB supplementation. These results suggest that CRB may exert a partial renoprotective effect against GTC-induced oxidative and apoptotic damage, possibly through its antioxidant and cytoprotective properties.

This study examined the effects of syringic acid (SA) against testicular toxicity induced by cadmium (CAD). In the study, once daily for 7 days, the control and CAD groups were administered sterile distilled water, while the CAD + SA and SA groups were administered 25 mg/kg SA. Additionally, on the first day of the study, saline solution was administered intraperitoneally to the control and SA groups, and 1.5 mg/kg CdCl ₂ was administered intraperitoneally to the CAD and CAD + SA groups. In blood, serum aspartate transaminase (AST) and alanine aminotransferase (ALT) enzyme activity, testosterone, creatine, and urea levels were evaluated. Spermatological parameters, including sperm motility, sperm viability, sperm concentration, and abnormal sperm, were evaluated. Histopathological examination and immunohistochemical analysis (inducible nitric oxide synthase (iNOS), cyclin D1, cannabinoid receptor1 (CB1)) were performed on testicular tissue. The testosterone value of the CAD group was significantly lower compared to the control and SA groups ( p < 0.0083). In the CAD + SA group, sperm motility, sperm vitality, and sperm concentration were significantly increased compared to the CAD group. In contrast, the percentages of abnormal sperm (head and tail) were significantly decreased in the CAD + SA group compared to the CAD group ( p < 0.0083). The rate of iNOS positivity in the SA and CAD + SA groups was similar to those in the control group. However, iNOS positivity was significantly higher in the testicles of the CAD group compared to the remaining groups ( p < 0.0083). In conclusion, SA can be used as a preventative agent against testicular toxicity caused by CAD.

This study aimed to investigate the effectiveness of 5-fluorouracil (5-FU) and Turkish propolis extract on the colon cancer model induced by azoxymethane (AOM) in Wistar rats. Study groups were designed as cancer group (AOM), control group, AOM+5-FU group, AOM+propolis group, AOM+Propolis+5-FU group. The findings showed that there was a significant decrease in WBC, and lymphocyte levels in the treatment groups AOM+5FU and AOM+Propolis+5FU compared to the AOM group (p˂0.0001, p˂0.005, respectively). The decrease in TAS level and increase in TOS level (p˂0.0001) were found to be significant in the AOM+Propolis+5FU group compared to the AOM group (p˂0.0001). Compared to the the AOM group, caspase-3, caspase-8 and Bax levels were significantly increased and BCL-2 level was significantly lower in the 5 AOM+Propolis+5FU group (p˂0.0001, p˂0.05, p˂0.0001, p˂0.0001, respectively). In the 5-FU and propolis used-therapy groups, decreased anaplasia in colonic cells. In conclusion, we strongly believe that as a chemotherapeutic, 5-FU, and propolis might have a stopper effect on cellular anaplasia over extrinsic apoptotical pathway. We also believe that this antiproliferative effect on cellular anaplasia can appear if the combined therapy is preferred. The therapeutic dose selection is clearly important for this.

Aims: This study aimed to investigate the possible effects of tramadol hydrochloride administration on the healing of colonic anastomosis after colonic ischemia-reperfusion injury in rats. Methods: Twenty-four Wistar albino male rats were divided into the control group (rats underwent resection-anastomosis after ischemia-reperfusion injury in the colon and saline was given intraperitoneally, n=12); and the TRA group (rats underwent resection-anastomosis after ischemia-reperfusion injury in the colon and tramadol hydrochloride was given, n=12). After colon ischemia-reperfusion injury was produced, the distal part of the descending colon was cut to full thickness, and the lumen was completely closed one by one with 6/0 polypropylene sutures. Then, 0.5 mL saline was administered to the control group and 30 mg/kg tramadol hydrochloride was administered to the TRA group intraperitoneally every day for five days. After sacrificing all the rats, the burst pressures were recorded, and blood serum and colon tissue samples were analyzed biochemically. Results: Biochemical analysis of blood serum samples revealed that IL-6 (p=0.026), MPO (p=0.001), CAT (p=0.024), and AST (serum p=0.002) levels were different between the two groups. Biochemical analysis of the tissue samples revealed that glutathione reductase (p=0.006), AST (p<0.001) and ALT (p=0.004) levels were different between the two groups. Conclusion: At the end of this study, it was thought that tramadol usage as an analgesic drug may not have a negative or positive therapeutic effect on colon ischemia-reperfusion injury and colon anastomosis in rats. Therefore, it was thought that tramadol hydrochloride could be used as an analgesic drug option in pain management in such patients.

Background and objective: This study aimed to assess the protective ability of edaravone on testicular torsion–detorsion injury in rats.Methods: Eighteen adult male Sprague–Dawley rats were randomly divided into three groups: Sham group (control, n = 6); testicular torsion/detorsion (T/D group, n = 6) and T/D+edaravone (T/D+E group, n = 6). The spermatic cords of rats of the T/D group and the T/D+E group were rotated 720° in a clockwise direction and maintained for 120 min in this torsion position. Around 90 min after the torsion, edaravone at a dose of 10 mg/kg dissolved in saline was administered IP to the T/D+E group. The testicle was counter‐rotated to its normal position to allow reperfusion for 4 h. Left testes of each animal were excised 240 min after beginning of reperfusion. Oxidative stress markers (TAS, TOS, SOD, and MDA) and apoptotic pathways (Caspase 3, Caspase 8, Caspase 9, Bcl‐2, and Bax,) were assessed by ELISA methods. Also, testicles were subjected to the histopathologic and ultrasound examinations.Results: Ultrasound imaging showed that edaravone reduced the surface area and increased vascularization in testicles with T/D (p < 0.0001, p < 0.05, respectively). Edaravone pretreatment markedly decreased the levels of MDA, TOS, Bcl‐2, Bax, Caspase 3, Caspase 8, and Caspase 9 (p < 0.0001). Also, it increased significantly TAS levels (p < 0.0001) and reduced insignificantly SOD activity. Histopathologic examinations demonstrated that edaravone significantly attenuated the histological damage caused by T/D in testicles.Conclusion: Taken together, the findings indicate that pretreatment of edaravone has protective effect against testicular T/D injury.

This study aimed to investigate the impact of hellebrin on human lung cancer cell (H1299) and breast cancer cell (MCF-7) lines over time. The viability of various concentrations of hellebrin (100 nM-400 nM) on two cancer cell lines was measured using the MTT method. The cellular proliferation over time was examined using xCELLigence real-time cell analysis (RTCA). The results showed a significant decrease in cell viability with increasing concentrations of hellebrin in both cancer cell lines compared to the control group (p˂0.0001). While the viability of both cancer cells decreased after a certain period of hellebrin application, the viability of the control groups increased over time. These findings indicate that hellebrin has high antiproliferative and cytotoxic effects on breast and lung cancer cells. Consequently, this study suggests that hellebrin may have potential as a treatment for other cancers, especially lung cancer, and further in vitro and in vivo experiments are needed to investigate this possibility.

Objectives: This study investigated the effect of krill oil (KO) on liver damage caused by acetaminophen (APAP). Methods: In the present study, the control and APAP groups were given distilled water by gavage for 14 days. In addition, the KO and APAP+KO groups were given 500 mg/kg krill oil by gavage for 14 days. At the end of 14 days, 0.9 % sodium chloride solution (saline solution) administration was applied intraperitoneally to the control and KO groups. Meanwhile, 220 mg/kg acetaminophen was administered to the APAP and APAP+KO groups. While some biochemical parameters in plasma were examined, some oxidative stress parameters in plasma and liver tissue were evaluated. Apoptotic and inflammatory responses of some primer sequences determined by quantitative Real-Time PCR (qPCR) in liver tissue. After histopathological examination of liver tissue, immunohistochemical analysis was performed with Wnt inhibitory factor-1 (Wif-1), beta-catenin (β-Catenin), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). Results: The Wif-1 positivity in hepatocytes increased significantly in the APAP group (5.29 ± 0.71) compared to the control (1.14 ± 0.51), and KO (2.14 ± 0.55) groups (p<0.001). The 8-OHdG positivity in hepatocytes increased significantly in the APAP group (19.57 ± 0.58) compared to the control (0.43 ± 0.20), KO (3.57 ± 0.48), and APAP+KO (4.00 ± 2.53) groups (p<0.001). Conclusions: As a result, krill oil could be used as a nutritional supplement to protect the liver against acetaminophen-induced liver injury.

In this study, it was aimed to investigate the effect of a poly(ethylene terephthalate)-g-poly(hydroxyethyl methacrylate) (PET-g-HEMA) nanofiber wound dressing modified with sericin-coated silver nanoparticles (S-AgNPs) on internal organs, oxidative stress, and biochemical parameters. To establish a burn model, the backs of anesthetized rats were shaved and then third-degree burns were created with a round-bottomed stainless steel rod 2 cm in diameter kept in 100 °C water for 20 seconds. The wounds of the negative control group (G1) were covered with standard bandages; the wounds of the positive control group (G2) were covered with SILVERCEL, used as burn wound material; and the wounds of the experimental group (G3) were covered with PET-based dressing material. Histopathological changes in organs (liver, kidneys, heart, pancreas, lungs), oxidative stress (total oxidant status, total antioxidant status, and nitric oxide), and biochemical parameters (serum aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyl transpeptidase [GGT], creatine kinase, lactate dehydrogenase, total protein, albumin, globulin, urea) were examined. Compared with the G1 group, plasma AST, ALT, and GGT levels were found to be significantly decreased in G2 and G3 (P<0.001). Plasma total antioxidant status was found to be significantly increased in G2 and G3 compared to G1 (P<0.05). Compared to the G1 group, degenerative and necrotic changes in the liver, kidneys, and pancreas were found to be significantly reduced in G2 and G3 (P<0.05). In conclusion, this work demonstrates that the synthesized PET-based wound dressing material has the capacity to be used commercially. Bu çalışmada, serisin kaplı gümüş nanopartiküller ile modifiye edilen poli(etilen tereftalat)-g-poli(hidroksietil metakrilat) (PET-g-HEMA) nanofiber yara pansuman malzemesinin iç organlar, oksidatif stres ve biyokimyasal parametreler üzerindeki etkisinin araştırılması amaçlandı. Yanık model oluşturmak için, anestezi altındaki sıçanların sırtı tıraş edildikten sonra 100 °C suda bekletilen 2 cm çapa sahip yuvarlak dipli paslanmaz çelik çubuk ile 20 saniye temas ettirildi ve sıçanların sırtlarında 3. derece yanık yaraları oluşturuldu. Negatif kontrol (sargı bezi) grubunun (G1) yarası standart sargı bezi, pozitif kontrol grubunun (G2) yarası yanık yara malzemesi olarak kullanılan silvercel ürünü ve deney grubunun (G3) yarası da PET tabanlı örtü malzemesi ile kapatıldı. Çalışmada organlar (karaciğer, böbrek, kalp, pankreas, akciğer) üzerindeki histopatolojik değişikler, oksidatif stres (TAS, TOS, NO) ve biyokimyasal parametreler (serum; AST, ALT, GGT, CK, LDH, total protein, albümin, globülin, üre) incelendi. G1 gubu ile karşılaştırıldığında, plazma AST, ALT ve GGT düzeyleri G2 ve G3 gruplarında anlamlı olarak azaldığı bulundu (P<0.001). Plazma TAS seviyesi, G1 grubuna kıyasla G2 ve G3 gruplarında anlamlı bir şekilde artığı bulundu (P<0.05). G1 gubu ile karşılaştırıldığında karaciğer, böbrek ve pankreastaki dejeneratif ve nekrotik değişikliklerin G2 ve G3 gruplarında anlamlı olarak azaldığı bulundu (P<0.05). Sonuç olarak; sentezlenen PET tabanlı yara örtü malzemesinin ticari olarak kullanılma kapasitesine sahip olduğunu göstermektedir.

Objective: Ovarian hyperstimulation syndrome is an iatrogenic condition that occurs in the treatment of infertility. There is no specific treatment available for OHSS. Cabergoline is a dopamine receptor 2 agonist and VEGF-VEGF2 receptor antagonist . Recently, cabergoline has been widely used to prevent the development of OHSS and reduce its severity Serotonin is known as a neurotransmitter and thought to have a role in the mechanism of angiogenesis and in signaling in endothelial cells. Serotonin is said to have similar effects to VEGF . Ondansetron is Selective Serotonin (5-HT3) Receptor Antagonist . It works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting. In the clinical practice today, there is no choice other than cabergoline, to prevent occurrence and reduce severity of OHSS, and sometimes its effects are limited. Methods: In our study, we compared the effect of cabergoline and ondansetron. 32 immature rats were used and the OHSS model was created. Parameters such as hematocrit value , ovarian size, the number of follicles in the ovary, endometrial capillary congestion and thickness values were evaluated and compared. Results: As a result, in our study, it was seen that ondansetron was effective on OHSS in many parameters. It is thought to be as effective as cabergoline. When we look at the literature, this is the first study in which ondansetron was evaluated for this purpose. It would be good to show this effect of ondansetron with other studies.

Bu çalışmada izoproterenol ile oluşturulan miyokard infarktüsüne karşı silimarin ve/veya borik asidin koruyucu veya tedavi edici etkilerinin karşılaştırılması amaçlanmıştır. GI ve GII gruplarına on dört gün boyunca gavaj ile oral yolla distile su verildi. On dört gün boyunca; GIII grubuna silimarin (100mg/kg) verilirken GIV grubuna borik asit (100mg/kg) verildi. Son gruba ise hem silimarin hem de borik asit on dört gün boyunca oral yolla (gavaj) verildi. Çalışmanın on üçüncü ve on dördüncü günü intraperitoneal yolla; GI grubuna izotonik uygulanırken, diğer gruplara subkutan izoproteranol (85mg/kg) uygulandı. Plazmadan; ALT, AST, Ca, CK, CHO, TP, Ing P, IL-6, IL-12, PAL-1 ve sPLA2 parametreleri değerlendirildi. Farelerden alınan kalp, akciğer, karaciğer, böbrek, dalak, cerebrum ve cerebellum dokularında histopatolojik inceleme yapıldı. CK düzeyi GII grubuna göre GIII grubunda anlamlı düzeyde azaldığı bulundu (P<0,05). Sonuç olarak isoproterenolun sebep olduğu miyokardiyal hasar sonucunda AST ve CK düzeylerinde artışlarına karşı tedavi gruplarında azalmalar görüldü. Bu özelliklerinden dolayı, silymarin ve boric asitin; miyokard enfarktüs durumlarına karşı koruyucu tedaviye katkı sağlayabileceği düşünülmektedir. This study aimed to compare the protective or therapeutic effects of silymarin and/or boric acid against myocardial infarction induced by isoproterenol. Distilled water was given orally by gavage to the GI and GII groups for fourteen days. The GIII group was received silymarin (100mg/kg), while the GIV group was given boric acid (100mg/kg) for 14 days. In the last group, both silymarin and boric acid were given orally (gavage) for fourteen days. On the thirteenth and fourteenth days of the study, while isotonic water was applied to the GI group, isoproterenol (85mg/kg) was applied to the other groups subcutaneously. Plasma ALT, AST, Ca, CK, CHO, TP, Ing P, IL-6, IL-12, PAL-1, and sPLA2 parameters were evaluated. Histopathological examination was performed on the heart, lung, liver, kidney, spleen, cerebrum, and cerebellum tissues taken from mice. The CK level was found to be significantly lower in the GIII and GV groups compared to the GII group (P<0.05). As a result, the increases shown in the plasma AST and CK activities caused due to the myocardial damage induced by isoproterenol were decreased in the treatment groups. Therefore it was thought that silymarin and boric acid may contribute to preventive treatment against myocardial infarction.