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Öğe (1 ? 3)-?-d-glucan enhances the toxicity induced by Bortezomib in rat testis(Blackwell Publishing Ltd, 2020) Abuç, Özlem Özgül; Koç, Kübra; Bal, Tuğba; Geyiko?lu, Fatime; Atilay, Hilal; Erol, Hüseyin Serkan; Yiğit, Serdar; Gül, Murat; Akaras, NurhanWe aimed to determine the possible effects of the antioxidant agent (1 ? 3)-?-D-glucan on bortezomib-induced rat testis damage. We used five groups of rats; control, (1 ? 3)-?-D-glucan (75 mg/kg), bortezomib group, bortezomib + (1 ? 3)-?-D-glucan groups (injection of (1 ? 3)-?-D-glucan after bortezomib and sacrificed at 48th or 72nd h). The effects of these substances were assessed by measuring the levels of the antioxidant enzymes and LPO, and by performing immunohistochemical analysis with NF-?B. The histology of testis was evaluated using aniline blue staining. (1 ? 3)-?-D-glucan leads to significant reductions in the levels of antioxidant enzymes and increased levels of LPO in testes. Moreover, it increased the NF-?B immunopositivity significantly in testis, especially in Bortezomib + (1 ? 3)-?-D-glucan group at 48th h. The histological changes were observed in the bortezomib and/or (1 ? 3)-?-D-glucan groups. Our results demonstrated that testis damage caused by the treatment with bortezomib was not eliminated by (1 ? 3)-?-D-glucan and shockingly it increased the damage. Practical applications: The testis damage caused by the treatment with bortezomib was not eliminated by (1 ? 3)-?-D-glucan and as a result, ?-1,3-(D)-glucan enhanced the toxicity by leading a decrease in the levels of GSH, SOD, and CAT, thus caused an elevation in the immunoreactivity of NF-?B and altered the histopathological changes by enhancing the toxic effects of bortezomib. The findings of the previous studies about the antioxidative activity of (1 ? 3)-?-D-glucan are controversial. So, it is necessary to consider the cytotoxicity of (1 ? 3)-?-D-glucan in testis tissue. Thus, more studies on testis tissue are necessary to confirm that (1 ? 3)-?-D-glucan is safe as an antioxidant.Öğe A histological and biochemical study of cumulus cells and the oocyte microenviroment in in vitro fertilization patients(Association of Clinical Biochemistry Specialists (Klinik Biyokimya Uzmanları Derneği), 2021) Akaras, Nurhan; Demirci, Tuba; Abuç, Özlem Özgül; 0000-0001-9852-8839; Halıcı, Mesut Bünyamin; Kaşali, KamberObjectives: The aim of this study was to investigate the effect of chemical changes in the follicular fluid and histological changes in the cumulus cells of the oocyte microenvironment on the number of oocytes in infertile patients. Methods: A total of 50 female patients aged 18-35 who presented at the Atatürk University Research Hospital Infertility Clinic and for infertility treatment were included. The patients were divided into 3 groups: Patients with fewer than 5 oocytes were classified as Group 1, patients with 5-20 oocytes comprised Group 2, and Group 3 was made up of patients with >20 oocytes. During the oocyte collection process, follicular fluid was aspirated from the follicles and the cumulus cells were collected. The follicular fluid was stored at -80°C for use in biochemical analysis of malondialdehyde (MDA), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH). Immunohistochemical staining was performed to examine caspase-3 and mechanistic target of rapamycin (mTOR) immunoreactivity at the stereological level. Results: The MDA level and total oxidant capacity (TOC) in the follicular fluid were higher in Group 1 patients than in the other 2 groups, while the SOD was lower (p<0.05). In Group 2 patients, the MDA level and TOS were higher than those of Group 3, while the SOD level was lower (p<0.05). The total antioxidant capacity (TAC) and GSH levels did not vary significantly according to the number of oocytes (p<0.05). Immunohistochemical staining showed that mTOR and caspase-3 immunoreactivity were more intense in Group 1 than in the other groups. Conclusion: The increase in mTOR expression may activate the caspase-3 pathway, which could lead to oxidative stress. The mTOR pathway may affect the oocyte countÖğe A histological and biochemical study of the protective role of hesperidin in testicular ischemia-reperfusion injury(Ali Cangül, 2023) Akaras, Nurhan; Şimşek, Hasan; Ordu, MelikeThis study aimed to investigate the possible effects of hesperidin on ischemia-reperfusion (IR) injury applied to rat testis. Methods: Twenty-eight Wistar albino rats were used and divided into four groups of seven each. Group 1: Sham surgery was performed on the right testis. Group 2: Hesperidin 100 mg/kg was administered intraperitoneally to rats. Group 3: After 1 h of ischemia and 4 h of reperfusion, the testicles were removed. Group 4: 100 mg/kg hesperidin was given 30 min before reperfusion. Biochemical, immunohistochemical, and histopathological analyzes were performed on testicles obtained from each group. Results: Total oxidant status (TOS) and oxidative stress index (OSI) levels increased significantly in the IR and IR-He groups (respectively, p=0.016, p=0.041; p=0.01, and p=0.024). TOS and OSI values in the hesperidin group decreased, although not statistically significant, compared to the IR group. Tumor necrosis factor-alpha (TNF-?) and nuclear factor kappa B (NF-kB) values were decreased in the hesperidin group compared to the IR group, although it was not statistically significant. Caspase-3 levels in testicular tissue were significantly increased in the IR group compared to the hesperidin group (p<0.05). While there were degenerative changes in the testicular tissue in the IR groups, a decrease in bleeding, congestion, edema, and degenerative changes was observed in the hesperidin-administered groups. Conclusion: Hesperidin reduced oxidative stress (decreased total oxidant level and OSI), inflammation (TNF-?), and apoptosis (NF-kB and caspase-3). According to these results, it was observed that hesperidin application had a protective effect on IR injury.Öğe Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis(Ali Cangül, 2023) Şimşek, Hasan; Akaras, NurhanGastric ulcer (GU) is a benign lesion in which excessive acid and pepsin activity affects the mucosal ep- ithelium and is common worldwide. Gastrointestinal disturbances come to the fore among the side effects observed in the treatment with drugs such as aspirin. Acacetin is a plant-derived flavonoid with intriguing properties such as anti-inflammatory, antioxidant, and anticancer. The aim of the study is to investigate the effects of acacetin in GU model caused by aspirin active ingredient acetylsalicylic acid. Methods: Thirty-two Wistar albino rats were divided into four groups: Control, GU, acacetin, and GU +acacetin. Acetyl- salicylic acid (150 mg/kg) and acacetin (25 mg/kg) were administered intraperitoneally as a single dose. Gastric lesions were examined microscopically and macroscopically. TNF-a, cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-kB) for inflammation; Caspase-3 and Bcl-2 for apoptosis, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) for oxidative stress were analyzed. Results: Bcl-2 and TAS values were decreased, while Tumor necrosis factor-alpha (TNF-?), COX-2, NF-kB, Caspase-3, TOS, and OSI values were increased in the GU group compared to the control group. Bcl-2 and TAS values were increased and TNF-?, COX-2, NF-kB, Caspase-3, TOS, and OSI values were decreased in the GU +acacetin group compared to the GU group. The GU index (GUI) detected in the GU group decreased significantly with the administration of acacetin. Conclusion: High doses of ASA contributed to the formation of GU in the stomach tissue by increasing the levels of inflammation, oxidative stress, and apoptosis, whereas ACA reduced the ulcer damage by reducing the increase in all these pathways.Öğe Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality(Elsevier, 2024) Akarsu, Serkan Ali; İleritürk, Mustafa; Küçükler, Sefa; Akaras, Nurhan; Gür, Cihan; Kandemir, Fatih MehmetIn this study, it was aimed to determine the effect of sinapic acid (SNP), a polyphenol with antioxidant, anti-inflammatory and antibacterial properties, on testicular damage caused by vancomycin (VCM), a widely used antibiotic against gram positive bacteria. A total of 35 male Sprague Dawley rats were used in the study, divided into five groups: control, VCM, SNP, VCM + SNP 10, and VCM + SNP 20. Following a week of oral administration, the rats were euthanized under sevoflurane anesthesia. While the VCM group had a significant increase in MDA levels, the SNP administration inhibited the increase in MDA levels. VCM led to a significant decrease in GSH levels, SOD, CAT, and GPx activity in the testicular tissue of rats, while SNP administration increased these antioxidant levels. SNP administration decreased the mRNA expression levels of VCM induced Nrf-2, HO-1, and NQO1 in testicular tissue while increasing the levels of MAPK14, MAPK15, JNK, P53, Apaf-1, Caspase-3, Caspase-6, Caspase-9, and Beclin-1 mRNA transcript levels. The VCM group showed a significant increase in Bax and NF-?B levels in testicular tissue, while Bcl-2 levels decreased. VCM significantly decreased sperm motility and increased the percentage of damaged sperm in rats. Histopathological results revealed that VCM caused disruption of basement membranes and disorganization of seminiferous tubules, but SNP administration preserved testicular histology. As a result, VCM increased oxidative stress, apoptosis, and autophagy in the testicular tissue of rats, altered testicular histopathology, and decreased sperm quality, while SNP decreased these effects.Öğe Anti-oxidant, Anti-inflammatory, and Anti-apoptotic Effects of Rutin in Spleen Toxicity Induced by Sodium Valproate in Rats(Bingöl Üniversitesi Fen Bilimleri Enstitüsü, 2023) Akaras, Nurhan; Kandemir, Fatih Mehmet; Şimşek, Hasan; Gür, Cihan; Aygörmez, SerpilLong-term exposure to sodium valproate, an anti-epileptic drug, causes toxic effects in tissues, especially by increasing oxidative stress and inflammation. Rutin is a flavanoid with anti- oxidant, anti-inflammatory and anti-apoptotic effects found naturally in many plants. In this study, we aimed to investigate the effects of rutin, a natural anti-oxidant, on sodium valproate- induced spleen tissue damage. 35 male rats were divided into 5 groups as control, sodium valproate, rutin, sodium valproate+Rutin 50 and sodium valproate+Rutin 100 groups. For 14 days, 500 mg/kg dose of sodium valproate and 50 or 100 mg/kg of rutin were administered by oral gavage. On day 15, spleen tissues were removed and biochemical methods, oxidative stress, inflammation and apoptotic parameters were analyzed and histologic analysis was performed. The levels of sodium valproate-induced oxidative stress, inflammation and apoptosis parameters increased in spleen tissues compared to the control group (p<0.05). With routine administration, all of these sodium valproate-induced increases were decreased (p<0.05). It was concluded that rutin has potential protective properties against the toxic effect caused by sodium valproate exposure in spleen tissues.Öğe Beneficial effects of Chrysin on Cadmium-induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways(Elsevier B.V., 2023) Şimşek, Hasan; Akaras, Nurhan; Gür, Cihan; Küçükler, Sefa; Kandemir, Fatih MehmetCadmium (Cd) is a toxic heavy metal that targets the kidney directly in the body. Chrysin (CHR) is a natural flavonoid with many properties such as antioxidant, anti-inflammatory and anti-apoptotic. The current study discloses new evidence as regards of the curative effects of CHR on Cd-induced nephrotoxicity by regulating oxidative stress, apoptosis, autophagy, and inflammation. Cd was administered orally at a dose of 25 mg/kg body weight alone or in combination with orally administered CHR (25 and 50 mg/kg body weight) for 7 days. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in renal tissue. Renal function tests were also evaluated. Cd caused an increase in serum toxicity markers, lipid peroxidation and a decrease in the activities of antioxidant enzymes. Nrf-2 triggered inflammatory responses by suppressing HO-1 and NQO1 mRNA transcripts and increasing NF-?B, TNF-?, IL-1? and iNOS mRNA transcripts. Cd caused inflammasome by increasing RAGE and NLRP3 mRNA transcripts. In addition, Cd application caused apoptosis by increasing Bax, Apaf-1 and Caspase-3 mRNA transcripts and decreasing Bcl-2 mRNA transcript level. It caused autophagy by increasing the activity of Beclin-1 level. CHR treatment had the opposite effect on all these values and reduced the damage caused by all these signal pathways. Overall, the data of this study indicate that renal damage associated with Cd toxicity could be ameliorated by CHR administration.Öğe Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite-induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats(Wiley, 2023) Gür, Cihan; Akarsu, Serkan Ali; Akaras, Nurhan; Tuncer, Sibel ÇiğdemArsenic (As) is a highly toxic metalloid. Carvacrol (CAR) is the active ingredient of Lamiaceae plants and has various biological and pharmacological properties. The present study investigated the protective effects of carvacrol (CAR) against testicular toxicity induced by sodium arsenite (SA). Rats were given SA (10 mg/kg) and/or CAR (25 or 50 mg/kg) for 14 days. Semen analyzes showed that CAR increased sperm motility and decreased the percentage of abnormal and dead sperm. It was determined that the oxidative stress induced by SA decreased with the increase of Nrf-2 and HO-1 expressions, SOD, CAT, GPx, and GSH levels, and MDA levels decreased after CAR treatment. It was observed that autophagy and inflammation triggered by SA in testicular tissue were alleviated by suppressing the expressions of LC3A, LC3B, MAPK-14, NF-?B, TNF-?, IL-1?, iNOS, and COX-2 biomarkers in rats given CAR. Also, CAR treatment suppressed SA-induced apoptosis by inhibiting Bax and Caspase-3 expressions in testicles and up-regulating Bcl-2 expression. Histopathological analyzes showed that rats given SA had deterioration in tubule structure and spermatogenesis cell line, especially a serious loss of spermatogonia cells, atrophy of seminiferous tubules, and deterioration of germinal epithelium. In the group given CAR, the germinal epithelium and connective tissue were in normal morphological structure and an increase in seminiferous tubule diameters was observed. As a result, it was determined that oxidative stress, inflammation, autophagy, and apoptosis induced by SA were suppressed by CAR, thus protecting the testicular tissue from damage and increasing semen quality.Öğe Carvacrol Reduces Mercuric Chloride-Induced Testicular Toxicity by Regulating Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Histopathological Changes(Springer, 2024) Şimşek, Hasan; Gür, Cihan; Küçükler, Sefa; İleritürk, Mustafa; Akaras, Nurhan; Öz, Mehmet; Kandemir, Fatih MehmetMercuric chloride (HgCl2) is a heavy metal that is toxic to the human body. Carvacrol (CAR) is a flavonoid found naturally in plants and has many biological and pharmacological activities including anti-inflammatory, antioxidant, and anticancer activities. This study aimed to investigate the efficacy of CAR in HgCl2-induced testicular tissue damage. HgCl2 was administered intraperitoneally at a dose of 1.23 mg/kg body weight alone or in combination with orally administered CAR (25 mg/kg and 50 mg/kg body weight) for 7 days. Biochemical and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and autophagy pathways in testicular tissue. CAR treatment increased HgCl2-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels. In addition, CAR reduced MDA levels, a marker of lipid peroxidation. CAR decreased the levels of inflammatory mediators NF-?B, TNF-?, IL-1?, COX-2, iNOS, MAPK14, MAPK15, and JNK. The increases in apoptotic Bax and Caspase-3 with HgCl2 exposure decreased with CAR, while the decreased antiapoptotic Bcl-2 level increased. CAR reduced HgCl2-induced autophagy damage by increasing Beclin-1, LC3A, and LC3B levels. Overall, the data from this study suggested that testicular tissue damage associated with HgCl2 toxicity can be mitigated by CAR administration.Öğe Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate.(Elsevier GmbH, 2023) Akarsu, Serkan Ali; Gür, Cihan; İleritürk, Mustafa; Akaras, Nurhan; Küçükler, Sefa; Kandemir, Fatih MehmetHeavy metals are one of the environmental pollutants. Lead (Pb) is one of the most common of these heavy metals. In this study, it was aimed at investigating the effects of syringic acid (SA) against testicular toxicity in rats administered lead acetate (PbAc). Methods: In the present study, a total of 35 Sprague-Dawley rats, 7 in each group, were used. The rats were divided into 5 groups, with 7 male rats in each group. Rats were given PbAc and SA orally for 7 days. The effects of PbAc and SA on epididymal sperm quality and apoptosis, inflammation, oxidative stress and histopathological changes in testicular tissue were determined. Results: While PbAc disrupted the seminiferous tubules and produced atrophic images, SA corrected these histological abnormalities. PbAc adminisration significantly reduced the levels of SOD, GSH, GPx, CAT, NRF-2 and NQO1 and significantly increased the levels of MDA and 8-OHdG in the testicular tissue of rats, while SA improved this situation. NF-?B, TNF-?, IL-1?, NLRP3, RAGE, ATF6, PERK, IRE1, CHOP, and GRP78 genes expression levels increased with PbAc administration, however these levels decreased with SA administration. In addition, PbAc increased the levels of apoptotic markers Bax, Caspase-3 and APAF-1 and decreased the level of Bcl-2, while SA improved this situation. It was observed that PbAc significantly reduced sperm quality in rats, while SA positively affected sperm quality. Conclusion: As a result, SA administered against PbAc-induced testicular dysfunction in rats can provide effective protection at doses of 25 mg/kg/bw and 50 mg/kg/bw.Öğe Effects of Bromelain on Oxidative Stress and Lung Tissue Histopathology in an Experimental Rat Sepsis Model(Afyon Kocatepe University, 2023) Akaras, Nurhan; Toktay, Erdem; Şimsek, Hasan; Celep Aydemir, Nevra; Yüce, NeslihanSepsis is an inflammatory syndrome that targets the lung tissue. Bromelain (BRO) is an enzyme complex known for its anti-inflammatory properties. In this study, the protective effect of BRO on lung injury due to sepsis induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats was investigated by biochemical and histopathological methods. Forty Sprague dawley rats were randomly divided into five groups as control, CLP, BRO, CLP+BRO 50 and CLP+BRO 100. In the study, after oral administration of 50 and 100 mg/kg BRO (total of 7 applications for 7 days) to rats, laparotomy and CLP were performed.Öğe Effects of Quercetin on Cypermethrin-Induced Stomach Injury: The Role of Oxidative Stress, Inflammation, and Apoptosis(Gümüşhane Üniversitesi, 2023) Akaras, Nurhan; Gür, Cihan; Şimşek, Hasan; Tuncer, Sibel ÇiğdemThis study was conducted to investigate the effects of quercetin (QUE) on cypermethrin (CYP) induced gastrotoxicity in rats. 35 Sprague-Dawley rats were randomly divided into five groups, 7 in each group. In the study, 25 and 50 mg/kg QUE were administered orally 30 min after 25 mg/kg cypermethrin was administered to rats for 28 days. Oxidative stress, inflammation, ER stress, apoptosis and autophagy markers were biochemically analyzed in gastric tissues. Additionally, histological analysis was performed for microscopic evaluation of gastric tissue. The results revealed that QUE prevented tissue damage by reducing CYP-induced lipid peroxidation (MDA) and increasing GSH, SOD, CAT and GPx activities. It also showed anti-inflammatory effect by suppressing inflammatory markers such as NF- B, IL-1?, TNF-?, iNOS and COX-2. QUE administration down-regulated CYP-induced increased PERK, ATF6, Caspase-3 and Beclin-1 markers. In addition, administration of QUE ameliorated the pathological tissue damage in gastric tissue due to CYP. The data of this study show that Que suppresses CYP-induced gastric toxicity by reducing oxidative stress, inflammation, ER stress, apoptosis a autophagy.Öğe Gossypin protects against renal Ischemia-Reperfusion Injury in rats(Kafkas University, 2020) Tanyeli, Ayhan; Eraslan, Ersen; Güler, Mustafa Can; Kurt, Nezahat; Akaras, NurhanRenal injury occurring as a result of renal ischemia-reperfusion may lead to renal failure or even death. The aim of this study is to investigate possible protective effects of Gossypin on tissue damage occurred due to ischemia-reperfusion in rat kidney tissue. A total of 48 male Wistar albino rats were used in the study. These rats were randomly divided into 6 groups equally (n = 8). The created groups were control (C), sham (S), ischemia-reperfusion (I/R), I/R + DMSO, I/R + 400 mu g/kg gossypin and I/R + 4 mg/kg gossypin. In the rats of sham group, the right nephrectomy was performed. In the rats of other groups rather than sham, the left renal artery was clamped after performing the right nephrectomy. Gossypin was administered intraperitoneally before the reperfusion. 24 h reperfusion was applied to the left renal after 1 h of ischemia. TNF-alpha, IL-1 beta, IL-6 and IL-10 levels were measured with spectrophotometric methods in the kidney tissues after the procedures were completed. Apoptosis and inflammatory pathways were evaluated histopathologically using Caspase 3 and NF-kappa B antibodies. There was a statistically significant decrease in IL-1 beta and IL-6 levels of the gossypin groups compared to the I/R group (P<0.05). As the level of TNF-alpha was decreased in the gossypin administered groups compared to the I/R group although not statistically significant, the level of IL-10 was increased. In the present study, we aimed to show that gossypin in renal I/R model is effective on inflammatory process and apoptosis and that it can be used in routine treatment to decrease the damage in all reasons that may cause I/R. In addition, this study can shed light on the studies to be done in this field in the future.Öğe Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress(Elsevier Inc., 2023) İleritürk, Mustafa; Kandemir, Özge; Akaras, Nurhan; Şimsek, Hasan; Genç, Aydın; Kandemir, Fatih MehmetPaclitaxel (PTX) is widely used to treat a number of malignancies, although it has toxic side effects. Hesperidin (HES) has a wide range of biological and pharmacological properties, including anti-inflammatory and antioxidant abilities. This research aims to investigate the role of HES in PTX-induced testicular toxicity. For 5 days, 2 mg/kg/bw i.p. of PTX was administered to induce testicular toxicity. Rats were administered oral dosages of 100 and 200 mg/kg/bw HES for 10 days after PTX injection. The mechanisms of inflammation, apoptosis, endoplasmic reticulum (ER) stress, and oxidants were investigated using biochemical, genetic, and histological techniques. As a result of PTX administration, decreased antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities and increased malondialdehyde level were regulated, and the severity of oxidative stress was reduced. NF-?B, IL-1? and TNF-? levels, which are among the increased inflammation parameters caused by PTX, decreased with HES administration. Although AKT2 gene expression decreased in PTX administered rats, it was determined that HES administration up-regulated AKT2 mRNA expression. Anti-apoptotic Bcl-2 decreased with PTX administration, and apoptotic Bax and Caspase-3 increased while HES administration reverted these effects towards control level. As a result of toxicity, the increase in ATF6, PERK, IRE1?, GRP78 levels caused prolonged ER stress, and this activity was diminished with HES and tended to regress. While all data were evaluated, Paclitaxel caused damage by increasing inflammation, apoptosis, ER stress and oxidant levels in testicular tissue, and Hesperidin showed a protective effect by correcting the deterioration in these levels.Öğe Naringin attenuates oxaliplatin-induced nephrotoxicity and hepatotoxicity: A molecular, biochemical, and histopathological approach in a rat model(Wiley, 2024) İleritürk, Mustafa; Kandemir, Özge; İleritürk, Duygu; Akaras, Nurhan; Şimşek, Hasan; Erdoğan, Ender; Kandemir, Fatih M.Oxaliplatin (OXL) is a significant therapy agent for the worldwide increase in cancer cases. Naringin (4?,5,7?trihydroxy flavonon 7?rhamnoglucoside, NRG) has a wide range of biological and pharmacological activities, including antioxidant and anti? inflammatory potentials. This research aimed to investigate NRG activity in OXL? induced hepatorenal toxicity. Accordingly, OXL (4 mg/kg b.w.) in 5% glucose was injected intraperitoneally on the first, second, fifth, and sixth days, and NRG (50 and 100 mg/kg b.w.) was given orally 30 min before to treatment. Biochemical, genetic, and histological methods were utilized to investigate the function tests, oxidant/ antioxidant status, inflammation, apoptosis, and endoplasmic reticulum (ER) stress pathways in kidney and liver tissues. Administration of NRG demonstrated an antioxidant effect by increasing the activities of OXL?induced reduced antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and decreasing the elevated lipid peroxidation parameter malondialdehyde levels. Nuclear factor??B, tumor necrosis factor??, interleukin?1?, and inducible nitric oxide synthase levels increased in OXL administered groups but reduced in NRG?treated groups. In the OXL?administered groups, NRG reduced the apoptosis?inducing factors Caspase?3 and B?cell lymphoma 2 (Bcl?2)?associated X protein levels, while elevating the antiapoptotic factor Bcl?2 levels. OXL triggered prolonged ER stress by increasing the levels of ER stress parameters activating transcription factor 6, protein kinase R?like ER kinase, inositol?requiring enzyme 1?, and glucose?regulated protein 78. Therefore, with the NRG administration, this activity was reduced and the ER stress level decreased. Taken together, it was found that OXL induced toxicity by increasing the levels of urea and creatinine, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase activities, inflammation, apoptosis, ER stress, and oxidants in the liver and kidney tissue, and NRG had a protective effect by reversing the deterioration in these pathways.Öğe Naringin protects against paclitaxel-induced toxicity in rat testicular tissues by regulating genes in pro-inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways(John Wiley and Sons Inc, 2024) Kankılıç, Nazım Abdülkadir; Küçükler, Sefa; Gür, Cihan; Akarsu, Serkan Ali; Akaras, Nurhan; Şimşek, Hasan; İleritürk, Mustafa; Kandemir, Fatih MehmetPaclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX-induced testicular toxicity. Thirty-five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX-induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1 beta, cyclooxygenase-2, interleukin-6, inducible-nitric oxide synthase, mitogen-activated protein kinase 14 (MAPK)14, MAPK15, c-Jun N-terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO-1, NQO1 and Bcl-2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX-induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX-induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy.Öğe Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole(Mashhad University of Medical Sciences, 2023) Taştan, Tu?ba Bal; Akaras, Nurhan; Demir, Özlem; Ugan, Rüstem AnılIn this study, the effects of astaxanthin on liver tissue in rats with polycystic ovary syndrome (PCOS) were evaluated. Materials and Methods: Fifty-four Spraque-Dawley rats were divided into 9 groups: Groups: Control, PCOS, PCOS+Metformin (Met), PCOS+ Astaxanthin (ASX)10, PCOS+ASX20, PCOS+ASX40, PCOS+Met+ASX10, PCOS+Met+ASX20, and PCOS+Met+ASX40. PCOS was induced in female rats by oral administration of letrozole (1 mg/kg) for 21 days. Rats were treated with ASX (10 mg/kg), ASX (20 mg/kg), ASX (40 mg/kg), and metformin (20 mg/kg) for 7 days after PCOS induction. At the end of the experiment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the liver tissue. The liver was stained with hematoxylin/eosin for histological examination. Additionally, NF-kB and caspase 3 were analyzed immunohistochemically. Results: A remarkable abnormality was observed in the biochemical and histological parameters in the liver tissue of the PCOS model rats. Astaxanthin dose-dependently normalized the MDA level. Additionally, astaxanthin showed a protective effect by increasing the SOD level and increasing its antioxidant activities. We observed that administration of astaxanthin in addition to metformin applied in the standard was more effective. Caspase 3 and NF-kB immune positivity was lower in the groups given astaxanthin compared with PCOS. Histologically, it was observed that astaxanthin improved the deteriorated liver morphology in the letrozole-induced PCOS group. Conclusion: According to our results, it was observed that astaxanthin had antioxidant, anti-inflammatory and anti-apoptotic effects on PCOS in the treatment groups. Therefore, it was concluded that astaxanthin may have a protective effect against PCOS side effects.Öğe Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology(Mashhad University of Medical Sciences, 2024) Akaras, Nurhan; Gür, Cihan; Çağlayan, Cüneyt; Kandemir, Fatih MehmetOxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate the possible protective effects of naringin (NRG) against OXL-induced testicular toxicity in rats. Materials and Methods: In the present study, rats were injected with OXL (4 mg/kg, b.w./day, IP) in 5% dextrose solution 30 min after oral administration of NRG (50 and 100 mg/kg, b.w./day) on the 1st, 2nd, 5th, and 6th days. Then, the rats were sacrificed on the 7th day and the testicular tissues were removed. Results: The results showed that NRG decreased (P<0.001) lipid peroxidation, increased (P<0.001) the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the levels of glutathione (GSH), and also maintained the testis histological architecture and integrity. NRG decreased the levels of apoptosis-related markers such as caspase-3, Bax, and Apaf-1 and increased Bcl2 in the OXL-induced testicular toxicity (P<0.001). In addition, NRG reversed the changes in mRNA transcript levels of oxidative stress, inflammation, and endoplasmic reticulum stress parameters such as Nrf2, HO-1, NQO1, RAGE, NLRP3, MAPK-14, STAT3, NF-?B, IL-1?, TNF-?, PERK, IRE1, ATF6, and GRP78 in OXL-induced testicular toxicity (P<0.001). Conclusion: Our results demonstrated that NRG can protect against OXL-induced testicular toxicity by enhancing the anti-oxidant defense system and suppressing apoptosis, inflammation, and endoplasmic reticulum stress.Öğe Protective effects of naringin on colistin-induced damage in rat testicular tissue: Modulating the levels of Nrf-2/HO-1, AKT-2/FOXO1A, Bax/Bcl2/Caspase-3, and Beclin-1/LC3A/LC3B signaling pathways(John Wiley and Sons Inc, 2024) Kankılıç, Nazım Abdülkadir; Şimşek, Hasan; Akaras, Nurhan; Gür, Cihan; İleritürk, Mustafa; Küçükler, Sefa; Akarsu, Serkan A.; Kandemir, Fatih M.Antimicrobial agent resistance has become a growing health issue across the world. Colistin (COL) is one of the drugs used in the treatment of multidrug-resistant bacteria resulting in toxic effects. Naringin (NRG), a natural flavonoid, has come to the fore as its antioxidant, anti-inflammatory, and antiapoptotic activities. The aim of the present study was to determine whether NRG has protective effects on COL-induced toxicity in testicular tissue. Thirty-five male Spraque rats were randomly divided into five groups (n = 7 per group): Control, COL, NRG, COL + NRG 50, COL + NRG 100. COL (15 mg/kg b.w., i.p., once per/day), and NRG (50 or 100 mg/kg, oral, b.w./once per/day) were administered for 7 days. The parameters of oxidative stress, inflammation, apoptosis, and autophagic damage were evaluated by using biochemical, molecular, western blot, and histological methods in testicular issues. NRG treatment reversed the increased malondialdehyde level and reduced antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione) levels due to COL administration (p < 0.001), and oxidative stress damage was mitigated. Nuclear factor erythroid 2-related factor-2 pathway, one of the antioxidant defence systems, was stimulated by NRG (p < 0.001). NRG treatment reduced the levels of markers for the pathways of apoptotic (p < 0.001) and autophagic (p < 0.001) damages induced by COL. Sperm viability and the live/dead ratio were reduced by COL but enhanced by NRG treatment. Testicular tissue integrity was damaged by COL but showed a tendency to improve by NRG. In conclusion, COL exhibited toxic effect on testicular tissue by elevating the levels of oxidative stress, apoptosis, autophagy, inflammation, and tissue damage. NRG demonstrated a protective effect by alleviating toxic damage.Öğe Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach(Springer Science and Business Media Deutschland GmbH, 2023) Şimşek, Hasan; Küçükler, Sefa; Gür, Cihan; Akaras, Nurhan; Kandemir, Fatih MehmetLead acetate (PbAc) is one of the top five most dangerous toxic heavy metals, particularly leading to kidney damage and posing serious health risks in both humans and animals. Sinapic acid (SNP) is a naturally occurring flavonoid found in fruits and vegetables that stands out with its antioxidant, anti-inflammatory, and anticancer properties. This is the first study to investigate the effects of SNP on oxidative stress, inflammation, apoptosis, autophagy and endoplasmic reticulum (ER) stress in PbAc-induced nephrotoxicity in rats by biochemical, molecular and histological methods. 35 Spraque dawley rats were randomly divided into five groups of 7 rats each: control, PbAc, SNP (10mg/kg), PbAc + SNP 5, PbAC + SNP 10. PbAc at a dose of 30 mg/kg body weight was administered via oral gavage alone or in combination with SNP (5 and 10 mg/kg body weight) via oral gavage for seven days. While PbAc impaired renal function by increasing serum urea and creatinine levels, SNP decreased these levels and contributed to the improvement in renal function. The administration of SNP reduced oxidative stress by increasing PbAc-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels, decreasing MDA levels, a marker of increased lipid peroxidation. SNP administration reduced NF-?B, TNF-?, IL-1?, NLRP3, and RAGE mRNA transcription levels, NF-?B, and TNF-? protein levels that are among the PbAc-induced increased inflammation parameters. Decreases in antiapoptotic Bcl-2 and increases in apoptotic Bax, APAF-1, and Caspase-3 due to PbAc exposure, SNP reversed the situation. SNP reduced ER stress caused by PbAc by increasing PERK, IRE1, ATF-6, CHOP, and GRP-78 levels and made it tend to regress. SNP reduced autophagy damage by decreasing the Beclin-1 protein level increased by PbAc. The findings of the present study suggested that SNP attenuates PbAc-induced nephrotoxicity.
