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Öğe Antioxidant, anti-inflammatory, and anti-apoptotic effects of crocin against doxorubicin-induced myocardial toxicity in rats(Springer Heidelberg, 2021) Abdulkareem Aljumaily, Sara Asaad; Demir, Mehmet; Elbe, Hulya; Yigitturk, Gurkan; Bicer, Yasemin; Altinoz, EyupDoxorubicin (DOX) is a well-known chemotherapeutic drug for most malignancies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. In the present study, we aimed to investigate the effects of crocin on doxorubicin-induced cardiotoxicity in rats. Forty rats were randomly divided into four groups: (a) control [received normal saline as a dose of 1 ml/kg by intraperitoneal injection (ip) for 15 days], (b) crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX+crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection, and crocin as a dose of 40 mg/kg/24h i.p for 15 days). As compared to the controls, the results showed that DOX administration caused significant increases in lipid indices [triglyseride (TG), low-dencity lipoproteins (LDL) (p<0.001), and very low-dencity lipoproteins (VLDL) (p<0.005)], oxidative stress parameters [malondialdehyde (MDA) and total oxidant status (TOS) (p<0.001)] and cardiac markers [creatine kinase-muscle/brain (CK-MB) and cardiac troponin I (cTnI) (p<0.001)]. Besides, significant decreases in antioxidant defense systems [glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) (p<0.001)] were observed. The present study also demonstrated that co-administration of crocin with DOX significantly ameliorated the lipid profile (p<0.005), cardiac markers (p<0.005), and oxidative stress indices (p<0.001) as compared to DOX group. Histopathologically, significant increase in the mean histopathological damage score (MHDS) was found in the DOX group as compared to the controls (p<0.001). In contrast, the administration of crocin with DOX alleviated MHDS in myocardium (p<0.001). Taken together, our results reveal that crocin might be a cardioprotective agent in DOX-treated patients for cancer.Öğe Beneficial role of crocin against doxorubicin-induced testicular damage in rats: insights into vimentin modulation(Cukurova Univ, Fac Medicine, 2024) ozgul-onal, Melike; Aljumaili, Sara Asaad Abdulkareem; Yigitturk, Gurkan; Yasar, Volkan; Bicer, Yasemin; Cetinavci, Dilan; Altinoez, EyupPurpose: Doxorubicin (DOX) is a wide-spectrum antibiotic used for chemotherapy. Its side effects limit treatment. Crocin is one of the carotenoids that has both anti-inflammatory and antioxidant activities. We aimed to evaluate the effects of crocin against doxorubicin-induced testicular damage in rats. Materials and Methods: Forty Wistar rats were divided into four groups. Group 1: Control, Group 2: Crocin, Group 3: DOX, Group 4: DOX+Crocin (n=10, for all). Testis tissues were stained with Hematoxylin-Eosin. The diameters of seminiferous tubules were measured and the testicular mean histopathologic damage score (MHDS) was calculated. Vimentin expression in Sertoli cells was calculated as H-Score. Levels of Malondialdehyde (MDA), Glutathione (GSH), Catalase (CAT), and Superoxide dismutase (SOD) activities were determined in testis tissues. Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were also calculated. Results: Atrophic seminiferous tubules were seen in the DOX group. Edema, vacuolization, and disorganization were present in the injured tubules. The MHDSs for the DOX group and control groups were 4.60 +/- 0.45 and 0.20 +/- 0.13, respectively. Both of these groups showed a significant difference. The histopathologic score was reduced after using crocin. Tubule damage considerably decreased while immunoexpression levels of vimentin and seminiferous tubule width significantly increased in the DOX+Crocin group compared to the DOX group. MDA and TOS levels were significantly increased after DOX treatment, and GSH, SOD, CAT, and TAS levels were significantly decreased. All biochemical indicators were greatly improved after receiving crocin. Conclusion: Crocin supplementation exhibited adequate beneficial effects against the testicular damage of DOXinduced function by balancing the oxidant/antioxidant status.Öğe Effects of pinealectomy and crocin treatment on rats with isoproterenol-induced myocardial infarction(Taylor & Francis Ltd, 2022) Demir, Mehmet; Altinoz, Eyup; Elbe, Hulya; Bicer, Yasemin; Yigitturk, Gurkan; Karayakali, Melike; Ballur, Arwa Fadil HaqiThe present study aimed to analyze the effects of pinealectomy and crocin treatment in isoproterenol-induced myocardial damage. Seventy rats were divided into seven groups: control, sham control, pinealectomy (PNX), isoproterenol (ISO; 85 mg/kg on the 29th and 30th days of the experiment, subcutaneous injection), PNX + ISO, PNX + crocin (50 mg/kg/day for 30 days, intragastric administration), and PNX + ISO + crocin. PNX procedure was performed on the first day of the study. A significant increase was observed in serum cardiac damage markers (CK-MB, Troponin I) after ISO administration. ISO administration led to a significant increase in cardiac oxidative stress parameters, such as malondialdehyde (MDA) and total oxidant status (TOS), while it led to a decrease in antioxidant defense system parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) when compared to control groups. Elevated MDA and TOS levels were observed, while reduced SOD and CAT activities, and decreased GSH and TAS levels were observed in the group that underwent PNX and ISO administration when compared to the PNX group. Furthermore, in the PNX + ISO + Crocin group, SOD and CAT activities, and GSH and TAS levels ameliorated and MDA and TOS levels were reduced with the crocin treatment when compared to the PNX + ISO group. Also, marked increases were observed in serum cardiac markers, histopathological and immunohistochemical findings after the crocin treatment. All findings demonstrated that crocin could be employed as a cardioprotective agent due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.Öğe Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis(Springer/Plenum Publishers, 2022) Ballur, Arwa Fadil Haqi; Altinoz, Eyup; Yigitturk, Gurkan; Onal, Melike Ozgul; Elbe, Hulya; Bicer, Yasemin; Karayakali, MelikeGout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and antioxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (on the 30th day, single-dose 20 mg/ml, intraperitoneal), MSU + MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU + PINX and MSU + PINX + MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status) were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU + MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.Öğe Neuroprotection by melatonin against acrylamide-induced brain damage in pinealectomized rats(Elsevier, 2022) Bicer, Yasemin; Elbe, Hulya; Karayakali, Melike; Yigitturk, Gurkan; Yilmaz, Umit; Cengil, Osman; Al Gburi, Mohammed Raed AbdullahThe current study aimed to evaluate the neuroprotective effect of exogenous melatonin against acrylamide (ACR)-induced oxidative stress and inflammatory and apoptotic responses in the brain tissues in pinealectomized rats (PINX). ACR is a toxic chemical carcinogen that occurs owing to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. The rats who underwent pinealectomy and sham pinealectomy were exposed to ACR (25 mg/kg b.w., orally) alone or with exogenous melatonin (10 mg/kg b.w., i.p.) for 21 consecutive days. Alterations of brain oxidant/antioxidant status, dopamine (DA), Brain-Derived Neurotropic Factor (BDNF) inflammatory mediator and apoptosis during exposure to ACR in pinealectomized rats were more than without pinealectomized rats. Histopathological changes were more in brain tissue of pinealectomized rats after ACR administration. Exogenous melatonin treatment in ACR-exposed rats following pinealectomy increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS) compared to PINX+ACR. Moreover, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in ACR-intoxicated brain tissues. In addition, after exposure to ACR on pinealectomized rats, melatonin treatment ameliorated BDNF and DA levels in brain tissues. Furthermore, exogenous melatonin intervention in ACR-intoxicated rats significantly rescued the architecture of neuronal tissues. In summary, the present study, for the first time, suggested that exogenous melatonin treatment could reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological alterations in the brain tissue of pinealectomized rats after ACR administration.Öğe Treatment with crocin suppresses diabetic nephropathy progression via modulating TGF-81 and oxidative stress in an experimental model of pinealectomized diabetic rats(Elsevier Ireland Ltd, 2022) Keelo, Rihab Mudhafar Ali Hammood; Elbe, Hulya; Bicer, Yasemin; Yigitturk, Gurkan; Koca, Oguzhan; Karayakali, Melike; Acar, DeryaOne of the most common complications of diabetes is diabetic nephropathy (DN). Uncontrolled hyperglycemia leads to histopathologic alterations in the kidney that prevent normal renal function. This study aimed to explore the effects of crocin treatment via virtue of its numerous beneficial properties in streptozotocin-induced pinealectomized diabetic rats. The pinealectomy procedure was conducted on the first day of the study. On the 30th day following pinealectomy, streptozotocin (STZ) (50 mg/kg) was administered intraperitoneally in Wistar rats for induction of diabetes. Diabetes was confirmed on the 3rd day following STZ administration by determining the glucose levels. Daily crocin treatment intraperitoneally for 15 days (50 mg/kg) ameliorated impaired renal oxidant/antioxidant balance, reduced TGF-81 immuno-staining around tubules, and promoted improvement of renal architecture. Moreover, crocin administration improved altered renal function parameters, including serum Cr and BUN, and also increased creatinine clearance. In conclusion, the protective effects of crocin on diabetic nephropathy might be associated with its powerful antioxidant properties, its ability to improve tissue antioxidant status, and its ability to prevent inflammatory pathways.
