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Emine Turkmen Samdanci,1 Mustafa Huz,1 Onural Ozhan,2 Kevser Tanbek,3 Esra Pamukcu,4 Ayse Nur Akatli,1 Hakan Parlakpinar21Department of Pathology, Inonu University School of Medicine, Malatya, Turkey; 2Department of Pharmacology, Inonu University School of Medicine, Malatya, Turkey; 3Department of Physiology, Inonu University School of Medicine, Malatya, Turkey; 4Department of Statistics, Firat University Faculty of Science, Elaziğ, TurkeyIntroduction and aim: Methotrexate (Mtx) is an antineoplastic and immunosuppressive drug that may cause hepatotoxicity, whereas molsidomine (Mol) is a vasodilating and antioxidant agent. This study aimed to investigate the potential protective effects of Mol in Mtx-induced liver toxicity in rats.Materials and methods: Forty Wistar albino rats were equally divided into five groups: control, Mol, Mtx, Mol–Mtx, and Mtx–Mol. Following treatment, the animals were sacrificed, and liver tissue samples were histopathologically evaluated using Roening grading and Bcl-2 antibody staining. Tissue oxidants, antioxidants, and serum transaminases were measured and statistically compared across all groups.Results: No hepatic fibrosis or steatosis was observed in any of the groups. In the Mtx group, grade 2 liver injury and score 2 Bcl-2 antibody staining were observed; however, in the Mol–Mtx group, these were lower (grade 1, score 1). There were no statistically significant differences in serum transaminase levels among groups. Malondialdehyde levels were higher in all rats that received Mtx, but no differences in myeloperoxidase levels were observed among the groups. Levels of tissue antioxidants, including superoxide dismutase, glutathione (GSH) peroxidase (GSH-Px), and reduced GSH, were significantly higher in the Mol-treated and Mol pre-treated groups. Catalase (CAT) levels were elevated in all Mol-treated groups, but only in that group were CAT levels statistically significantly higher than in the control group.Conclusion: Our results suggest that some oxidant levels could increase following Mtx administration in the liver, possibly contributing to liver damage, whereas Mol could mitigate the histopathological and biochemical effects of hepatotoxicity. However, molecular studies are required to understand the exact mechanisms of these alterations.Keywords: methotrexate, molsidomine, hepatotoxicity, hepatic fibrosis

Engin Burak Selçuk,1 Meltem Sungu,2 Hakan Parlakpinar,3 Necip Ermiş,4 Elif Taslıdere,5 Nigar Vardı,5 Murat Yalçinsoy,6 Mustafa Sagır,3 Alaaddin Polat,7 Mehmet Karatas,8 Burcu Kayhan-Tetik11Department of Family Medicine, 2Inonu University Medical Faculty, Malatya, Turkey; 3Department of Pharmacology, 4Department of Cardiology, 5Department of Histology and Embryology, 6Department of Pulmonary Medicine, 7Department of Physiology, 8Department of Medical Ethics, Inonu University Medical Faculty, Malatya, TurkeyBackground: Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events.Objective: To determine the cardiovascular toxicity induced by varenicline in rats.Materials and methods: We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 µg/kg/day varenicline on days 1–3, 9 µg/kg twice daily on days 4–7, and 18 µg/kg twice daily on days 8–90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed.Results: Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups.Conclusion: Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation.Keywords: varenicline, smoking, cardiovascular, rat, electrocardiogram, histopathological evaluation

OBJECTIVE: The aim of this study was to investigate the effects of cinnamon bark essential oil (CBO) on analgesia, motor activity, balance, and coordination in rats with sciatic nerve damage. MATERIALS AND METHODS: Rats were divided into three groups as simply randomized. The right sciatic nerve (RSN) of the Sham group was explored. Only vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury (SNI) group was explored. Damage was created by unilateral clamping, and vehicle solution was applied for 28 days. The RSN of the sciatic nerve injury+cinnamon bark essential oil (SNI+CBO) group was explored. SNI was created by unilateral clamping and CBO was applied for 28 days. In the experiment study, motor activity, balance, and coordination measurements were made with rotarod and accelerod tests. A hot plate test was performed for analgesia measurements. Histopathology studies were carried out with the sciatic nerve tissues. RESULTS: In the rotarod test, there was a statistically significant difference between the SNI group and the SNI+CBO group (p<0.05). According to the accelerod test findings, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups. In the hot plate test, there was a statistically significant difference between the SNI group with the Sham and SNI+CBO groups (p<0.05). In comparison to the Sham group and the SNI group, the SNI+CBO group was shown to have the greatest expression level of vimentin. CONCLUSIONS: We have concluded that CBO can be used as an adjuvant treatment in cases of SNI, increased pain, nociception, impaired balance, motor activity, and coordination. Our results will be supported by further studies. [ABSTRACT FROM AUTHOR]

Primary or metastatic hepatic malignancies are common. Partial hepatectomy (PH) is the primary treatment for both benign and malignant hepatic neoplasms; it also is used for living donor liver transplantation. The regenerative potential of the liver after PH is 70–80% in humans. We investigated the protective and therapeutic effects of agomelatine (AGM) on rat liver regeneration following PH. We used 32 rats distributed equally into four groups: group 1, sham control; group 2, PH group; group 3, administered 20 mg/kg AGM orally once/day for 7 days following PH; group 4, administered 20 mg/kg AGM orally once/day 3 days before and 7 days following PH for 10 days. Liver samples were analyzed for antioxidants and free radicals. Tissue samples were processed and stained with hematoxylin and eosin to assess histopathological status and stained immunohistochemically for Ki-67. We found that PH reduced antioxidant enzymes and increased tissue reactive oxygen species, whereas AGM treatment had the opposite effect on these parameters. Our biochemical and histopathological findings were consistent. PH caused sinusoid congestion and dilation. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas these were reduced in group 4. Intensity of Ki-67 immunostaining of hepatocytes was increased in group 2, whereas it was reduced in the group 4 compared to group 1. We found that AGM was hepatoprotective following PH due to its antioxidant and free radical scavenger properties. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was performed to investigate the potential beneficial effects of thymoquinone (TQ) on brain tissue based on biochemical and histopathological analyses in cisplatin (CIS) treated rats with central nervous system (CNS) neurotoxicity. MATERIALS AND METHODS: The rats were randomly divided into 4 groups with 8 rats in each group (n:8). Group 1: (Control), saline was administered for 3 days at a volume of 0.5 ml per day intraperitoneal (i.p.). Group 2: (CIS Group), one dose of CIS was administered (7 mg/kg i.p.). Group 3: (TQ Group), TQ was given at a dose of 5 mg/kg per day for 3 days (i.p.). Group 4: (CIS+TQ Group), one dose of 7 mg/ kg was initiated half an hour before administration of CIS and one dose of 5 mg/kg per day was administered TQ i.p. for 3 days. RESULTS: Malondialdehyde levels were found to be statistically significantly higher in the CIS group compared to the control group. Degenerative changes observed in the CIS+TQ group were found to be milder than in the CIS group. In the CIS+TQ group, a statistically significant decrease in the severity of caspase-3 immunoreactivity was found when compared to the CIS group. It was found that the severity of neurofilament immunoreactivity monitored in neuronal extensions was similar in all groups. In the CIS+TQ group, the severity of tau protein’s immunoreactivity was similar to that of the CIS-group. CONCLUSIONS: According to the results obtained in our study, beneficial effects were obtained in reducing neurotoxicity with shortterm TQ application in rats treated with CIS treatment. [ABSTRACT FROM AUTHOR]

Hyperglycemia increases reactive oxygen species (ROS) and the resulting oxidative stress contributes to the development of diabetic complications. Dexpanthenol (Dxp) is the biological active form of pantothenic acid. We investigated whether Dxp administration could decrease oxidative stress as a way to treat renal complications of diabetes mellitus (DM). Thirty-two male Wistar albino rats were divided into four groups: control, Dxp, DM and DM + Dxp. Experimental diabetes was induced by a single dose of streptozotocin (STZ). After administration of STZ, the DM + Dxp group was administered 500 mg/kg Dxp intraperitoneally every day for 6 weeks. At the end of the study, blood glucose levels were measured and rats were sacrificed. Kidneys were embedded in paraffin, sectioned and stained with hematoxylin and eosin, and periodic acid-Schiff. The mean malondialdehyde levels, glutathione peroxidase, superoxide dismutase and catalase activities, and total antioxidant and total oxidant status also were measured. The control group was normal in histological appearance. We observed congestion, inflammation, glomerulosclerosis, tubular desquamation, loss of villi and hydropic degeneration in tubule cells in the DM group. Indicators of oxidative stress were elevated and antioxidant activity was reduced in the DM group compared to controls. In the DM + Dxp group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced compared to the DM group. We found that Dxp exhibited ameliorative effects on STZ induced diabetic nephropathy by increasing antioxidant activity. [ABSTRACT FROM AUTHOR]

This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine ( AG), on radiotherapy ( RT)-induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+ RT and (v) RT+ AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde ( MDA), superoxide dismutase ( SOD), catalase ( CAT), glutathione peroxidase ( GPX), glutathione ( GSH), total oxidant status ( TOS), total antioxidant capacity, oxidative stress index ( OSI), blood urea nitrogen ( BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT-treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT-treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT-treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT-induced kidney and testis injury. [ABSTRACT FROM AUTHOR]

Background and aims: Radiation colitis typically emerges during radiotherapy of intra-abdominal malignancies. While the underlying mechanism remains unclear, it is considered that free oxygen radicals act like cellular mediators to cause colonic damage. Apocynin (APO) prevents oxidative stress and apoptotic cell death by inhibiting NADPH oxidase, and preventing the formation of free oxygen radicals. The aim of the present study was to investigate the protective effect of APO, a strong antioxidant and antiinflammatory agent, on radiation induced colonic oxidative damage in rats. Materials and methods: Rats were randomly divided into four groups (n = 8/group). Group I (control group); Group II (Group RAD) received a single dose of 800 cGy ionizing radiation to the whole abdomen with a linear accelerator (LINAC); Group III (Group APO) received a single dose of 20 mg/kg of APO intraperitoneally for five days; Group IV (Group APO+RAD) received APO for five days before radiation exposure (similar to Group III), (similar to Group II). Results: APO treatment prior to radiation led to protection in the biochemical and histopathological parameters. Conclusions: Our study shows that APO treatment before radiation improves radiation induced colonic injury in rats, by decreasing oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the acute effect of high-dose acetylsalicylic acid (ASA) on kidney and testis, and the potential protective and therapeutic effects of melatonin on ASA-related pathology. A total of 40 rats were randomly divided into the following 5 groups (n = 8): group 1: control, not given any drug; group 2: only 200 mg/kg ASA was given; group 3: 5 mg/kg melatonin was given 45 min before administering 200 mg/kg ASA; group 4: 5 mg/kg melatonin was given 45 min after administering 200 mg/kg ASA; and group 5: only 5 mg/kg melatonin was given. The histopathological changes and the biochemical findings; such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), and blood urea nitrogen (BUN) as well as serum creatinine (Cr) levels were evaluated. ASA significantly increased MDA levels in both kidney and testis, whereas it significantly decreased the values of SOD, CAT, GPX, and GSH in kidney and CAT levels in testis. Melatonin significantly decreased MDA levels in kidney and ameliorated it in testis, whereas it caused elevation in the levels of antioxidants. BUN and Cr levels were higher after ASA, whereas these levels were diminished after melatonin administration. The improvement obtained by melatonin on ASA-induced histological alterations was more prominent when it was used after ASA in kidney and before ASA in testis. In this study, we demonstrated the beneficial effect of melatonin on high-dose ASA-related pathology of kidney and testis for the first time. [ABSTRACT FROM AUTHOR]

BACKGROUND, It is generally agreed that physiological levels of melatonin, a hormone secreted by the pineal gland, are important in protecting against oxidative stress-induced tissue damage. AIM, We investigated the effects that pinealectomy and the administration of exogenous melatonin have on the brains, testes, duodena and stomachs of rats. MATERIALS AND METHODS, Pinealectomized (Px) and sham-operated (non-Px) rats were used.We evaluated structural changes, and catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD) and malondialdehyde (MDA) levels. The rats were divided into the following five groups (eight rats in each group): sham (non-Px), Px+ vehicle, Px+ melatonin (10 mg/kg given daily intraperitoneally for a week), melatonin and ethyl alcohol. RESULTS, The antioxidant levels in the tissue of Px rats were significantly lower than in those of the sham group. Administering melatonin significantly increased antioxidant levels (p < 0.05). The Px rats also showed a significant increase in MDA levels when compared to the sham group, and administering melatonin to the Px rats significantly reduced their MDA levels (p < 0.05). The severity of caspase-3 staining was lower in the Px+ melatonin group than in the Px+vehicle group. CONCLUSIONS, These findings suggest that significantly more oxidative and structural changes occur in rats' brains, spinal cords and testes after pinealectomy, but that this can be diminished by melatonin treatment. However, Px does not have important effects on the duodenum and stomach. [ABSTRACT FROM AUTHOR]

Objectives: To explore the protective and curative effects of dexpanthenol (DEX) on isoproterenol (ISO)-induced cardiac damage in rat heart. Methods: Forty rats were randomized into four groups (n=10): control group; ISO group (150 mg/kg); DEX+ISO group (DEX 250 mg/kg administrated 30 minutes before the repetitive two single dose of ISO in first two days, than DEX continued for 2 days); ISO+DEX group (2 days after the repetitive two single dose of ISO and DEX continued for 2 days). Rats were monitored for mean arterial blood pressure, heart rate, O2 saturation, and electrocardiography. Heart tissue levels of malonilaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and reduced glutathione (GSH) were determined. Results: Blood pressure and O2 saturation values indicated a significant decrease in the ISO group compared to the control group. T wave negativity was observed in 6 of 10 rats in the ISO group, in 1 of 10 rats in the ISO+DEX group, and none of 10 rats in the DEX+ISO group. SOD and GPX levels were significantly lower in the ISO group compared to the control and the DEX+ISO groups. CAT levels were significant decrease in the ISO group compared to the control group. ISO administration induced morphological alterations such as disorganization of cardiomyocytes, loss of myofibrils and cytoplasmic vacuolization in the heart. On the other hand, the histological damage was significantly decreased in the ISO+DEX and DEX+ISO groups when compared to the ISO group. Conclusion: This study implies the cardioprotective effects of DEX on ISO-induced cardiotoxicity. Acknowledge: This study was supported by TUBITAK (The Scientific and Technological Research Council of Turkey, project number: 2209/A-2012, belongs to Ferhat Kalkan). [ABSTRACT FROM AUTHOR]

Background: Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor., Objectives: We aimed to investigate the effects of the alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH., Methods: The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed., Results: Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it., Conclusion: ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure.