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Aim: This study aimed to investigate the potential protective effects of N-acetyl-L-cysteine (NAC) against apical periodontitis (AP) in rats with adriamycin (ADR)-induced kidney and heart diseases., Methodology: Fourty-eight Wistar albino rats were divided into six groups: (1) Control group, (2) ADR group (1 mg/kg/day ip for 10 days), (3) AP Group (1st mandibular molar tooth), (4) AP + ADR Group, (5) AP + NAC group (150 mg/kg/day ip), and (6) AP + ADR + NAC group. After 3 weeks, the rats were decapitated and blood and tissue samples (heart, kidney, and jaw) were collected. Tissue samples were evaluated by biochemical (inflammatory cytokines and hemodynamic parameters) and radiological analyses. One-way anova with Tukey post hoc tests was used to compare data, considering p < .05 as statistically significant., Results: The serum levels of TNF-α, IL-1β, BUN, Creatinine, CK, and LDH were elevated in the test groups compared with the control group, and treatment with NAC reduced these levels (p < .05). Heart and kidney tissue analysis showed a higher heart-to-body weight ratio (HW/BW) and kidney-to-body weight ratio (KW/BW) in the test groups compared with the control group (p < .05). No significant differences in HW/BW and KW/BW were found between the control and AP + NAC groups. Volumetric apical bone resorption analysis showed an increase in periapical radiolucencies in AP-induced groups indicating apical periodontitis. NAC treatment reduced the total area and volume of resorption cavities (p < .05)., Conclusions: The results suggest that NAC's antioxidant and anti-inflammatory effects can reduce adriamycin-mediated heart and kidney damage and may have a positive effect on apical periodontitis in individuals with nephropathy and cardiomyopathy., (© 2023 British Endodontic Society. Published by John Wiley & Sons Ltd.)

Purpose: Several substances that have anti-inflammatory, antiproteinase, and anti-infective properties have been evaluated as modulators of the inflammatory response in periodontal disease. However, evidence for the anti-inflammatory and antioxidative activities of bromelain is limited. This study evaluated the impact of systemically administered bromelain on the progression of experimental periodontitis., Methods: Four equal groups of 32 Wistar albino rats were created as follows (n = 8): control, periodontitis + saline, periodontitis + 5 mg/kg/day bromelain, and periodontitis + 10 mg/kg/day bromelain. To quantify the resorption of bone and bone volume/tissue volume, bone surface / bone volume, and connectivity, lower jawbones were fixed and then scanned using microcomputed tomography (micro CT). Blood samples were taken to measure the macrophage colony-stimulating factor(M-CSF) concentrations, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-8 (MMP-8), interleukin-6(IL-6), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological assessments were made to examine the tissue., Results: Treatment with bromelain improved the healing of the periodontium by decreasing the number of leukocytes and ligament deterioration in the gingival connective tissue and by supporting reintegration with alveolar bone. Bromelain used in ligature-induced periodontitis reduced alveolar bone (AB) resorption as measured by microCT; reduced inflammatory parameters such as IL-6 and TNF-α; regulated oxidative-antioxidative processes by increasing GPx and SOD and reducing MDA levels; and regulated AB modeling by decreasing M-CSF, RANKL, and MMP-8 and increasing OPG levels., Conclusion: Bromelain may be an option in periodontal therapy by regulating cytokine levels, improving the healing process, and reducing bone resorption and oxidative stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The purpose of the study was to investigate the therapeutic effects of α-lipoic acid (ALA) on an induced-acute pulpitis model in rats. Twenty-four Wistar albino rats were randomly divided into three groups: control, induced-acute pulpitis (PULP) and PULP + ALA groups. In the PULP and PULP + ALA groups, the crowns of the maxillary left incisors were removed horizontally. All exposed pulp tissues were treated with 5 µL LPS solution. In the PULP + ALA group, the rats were treated intraperitoneally with a single dose of ALA (100 mg/kg). The rats were sacrificed 24 h after pulp injury, and the trunk blood and pulp samples were collected and then determined using ELISA assay kits. TNF-α, IL-1β, MMP-1 and MMP-2 levels in the serum and pulp tissues were considerably higher in the PULP group than the control group (p < 0.01-0.001). In the PULP + ALA group, TNF-α, IL-1β, MMP-1 and MMP-2 levels in the serum and pulp tissues decreased significantly compared to the PULP group (p < 0.05-0.001). ALA decreases pro-inflammatory mediators and proteolytic enzymes, which might relieve acute inflammation., (© 2022 Australian Society of Endodontology Inc.)

The aim of the present study was to evaluate the inhibitory effects of oxytocin on the development of periodontitis based on its properties against bone loss and resorption. Thirty-two Wistar albino rats were divided into four equal groups: control, periodontitis + saline, periodontitis + 0.5 mg/kg/day oxytocin, and periodontitis + 1 mg/kg/day oxytocin. Periodontitis groups received 4.0 silk ligatures around their cervixes of the right and left mandibular incisors in an "8" shape, kept for 14 days. Animals in oxytocin groups were injected once every day during 14 days with oxytocin. The mandibles were fixed and scanned using microcomputed tomography to quantify bone resorption and volumetric measurements. Blood samples were collected to analyze the concentrations of macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κΒ ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase-8 (MMP-8), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological evaluations were conducted to examine the gingiva and alveolar bone. Oxytocin prevented the development of periodontitis by decreasing ligament deteriorations and leukocytes in the gingival connective tissue and promoting reintegration with the alveolar bone. Bone resorption in all regions was less in the periodontitis + 1 mg/kg/day oxytocin group than in the periodontitis + saline group. Although TNF-α, IL-6, and RANKL values were lower in the periodontitis + 1 mg/kg/day oxytocin group, OPG was higher than that in the periodontitis + saline group. M-CSF, MMP-8, and MDA were lower in the oxytocin groups than in the periodontitis + saline group. Oxytocin may be an effective agent for periodontal diseases because it decreased bone resorption, oxidative stress, and inflammation in an experimental periodontitis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Irinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. N -acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress and inflammation. This study aimed at investigating whether NAC provides protection against hepatorenal and gastrointestinal tissue damage induced by CPT-11. Thirty-two Wistar albino rats were divided into four groups as control, NAC, CPT-11, and CPT-11+NAC. Following the experimental period, blood, and tissue samples (liver, kidney, stomach, and small intestine) were collected, and biochemical indicators, together with pro-inflammatory cytokines (TNF-α and IL-1β), matrix metalloproteinases (MMPs), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels were evaluated. Both the biochemical indicators and the pro-inflammatory cytokines, MMP, and MDA levels increased in animals treated with CPT-11, while SOD and GPx activities decreased. Histopathological evaluation revealed structural damage in all examined tissues. With NAC administration, significant improvements were observed, both biochemically and histologically. In conclusion, the results of the present study suggest that NAC treatment together with CPT-11 may have a beneficial effect on reducing CPT-11 toxicity in rats, by modulating inflammation and the oxidant-antioxidant balance. These results strongly promote further investigative studies.

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) is an inflammasome associated with oral and general health. There is a bidirectional relationship between the oral cavity and systemic health. The primary reason for this situation is the similarity in pathways for chronic inflammatory diseases both in the oral cavity and systemically. Periodontal and periapical diseases are some of the most common inflammatory conditions in adults and are associated with bacterial infection and host inflammation. The pathogenesis of periodontal and periapical lesions is complex and multifactorial, and the host inflammatory response determines the progression and pattern of the diseases. Inflammasomes, innate immune system receptors and sensors, are the key components in the pathogenesis of the inflammatory conditions. They are reported to be responsible for the initiation of the inflammatory reaction, maturation of proinflammatory cytokines and pyroptosis. The NLRP3 inflammasome is a multi-protein complex that contributes to immune responses during infection or injury. NLRP3 is implicated in several diseases such as diabetes, rheumatoid arthritis, cardiovascular diseases, inflammatory bowel diseases, multiple sclerosis, and Alzheimer's disease. There have been many recent advances in our knowledge concerning the essential role of NLRP3 inflammasome in periodontal and periapical inflammation. Therefore, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. This paper will provide an overview of the role of NLRP3 inflammasome on periodontal and endodontic diseases with their links between systemic conditions, and presents a future perspective for the treatment of these inflammatory conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Alpha-lipoic acid (ALA) is extensively utilized in multivitamin formulas and anti-aging products. The purpose of this study was to investigate the potential protective benefits of ALA on 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats. Tissues from the stomach, small intestine, and large intestine were excised, and blood sera were obtained to identify biochemical indices such as TNF-α, IL-1β, MDA, GPx, SOD, MMP-1, -2, -8, and TIMP-1. A histopathological study was also performed. The results revealed mucositis-elevated TNF-, IL-1, MDA, MMP-1, -2, -8, and TIMP-1 levels in both tissues and sera, and these values dropped dramatically following ALA treatment. Reduced SOD and GPx activities in mucositis groups were reversed in ALA-treated groups. The damage produced by mucositis in the stomach and small intestine regressed in the ALA-treated group, according to histopathological evaluation. Consequently, the implementation of ALA supplementation in 5-FU therapy may act as a protective intervention for cancer patients with gastrointestinal mucositis. In light of the findings, ALA, a food-derived antioxidant with pleiotropic properties, may be an effective treatment for 5-FU-induced gastrointestinal mucositus, and prevent oxidative stress, inflammation, and tissue damage in cancer patients receiving 5-FU therapy.

Objectives: Ischemia-reperfusion injury is a life-threatening clinical problem that can occur after transplantation or a number of clinical procedures. The purpose of the study was to investigate the effects of Ambroxol on kidney damage caused by experimentally induced ischemia-reperfusion injury in rats., Materials and Methods: Wistar albino rats were divided into 3 groups: Control (CTR, n=6), Kidney ischemia-reperfusion (K-IR, n=6), And kidney ischemia reperfusion+Ambroxol (K-IR+AMB, n=6). In K-IR+AMB group, Ambroxol (30 mg/kg) was administered orally 30 min before the ischemia period. K-IR and K-IR+AMB groups underwent 45 min of kidney ischemia followed by a 6-hour reperfusion period. At the end of the reperfusion period, blood and kidney tissue samples were collected after euthanasia. From the blood samples, BUN and creatinine levels were determined to assess kidney function, and TNF-α and IL-1β concentrations were evaluated to determine inflammatory response., Results: While serum BUN, creatinine activities, and TNF-α and IL-1β concentrations were higher in both IR groups compared with the CTR group, these values were found to be lower in the K-IR+AMB group compared with the K-IR group. Histopathological examination revealed that interstitial edema and desquamation of tubular cells in the K-IR group were more severe than in the K-IR+AMB group., Conclusion: Ambroxol treatment alleviated the production of pro-inflammatory cytokines and the harmful cellular effects in the tubular cells., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX., Methods and Results: Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group., Conclusion: It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: In some cases, the tongue and oesophagus tissues are damaged by the corrosive burn. Surgical interventions may cause scar formation, and severe burns treatment methods are limited. This study aims to investigate bromelain, a phytotherapeutic product, on the corrosive burn as a non-surgical option and as an adjunctive therapy, insofar as the treatment of corrosive wounds is not limited only to the treatment of oxidative stress and inflammatory reactions., Methods: On the tongues of Wistar albino rats, chemically produced oral ulcers were created by topical application of NaOH (40%) solution, and in the distal oesophagus same mixture was applied to produce a corrosive oesophageal burn. For a week, they were treated orally by bromelain (100 mg/kg/day) or saline solution. At the end of seven days, animals were decapitated to remove the tongue and oesophagus, and blood samples were collected to obtain serum. Myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) concentrations were measured in serum, and luminol and lucigenin chemiluminescence (CL) were measured in tissue samples., Results: MDA and CL values were significantly increased, and GSH levels in tissue significantly decreased due to the corrosive burns. Saline treated corrosive burn group measured higher in the serum cytokines in according to the control group., Conclusions: Bromelain administration decreased oxidant and inflammatory parameters and increased antioxidant levels in NaOH-induced corrosive burns. Thus, we concluded that bromelain may protect the tongue and oesophagus tissues with its anti-inflammatory and antioxidant effects., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

Daily new information emerges regarding the COVID-19, infection of SARS-CoV-2, which is considered a global pandemic. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are required to complete the viral invasion pathway and are present in the oral mucosa, gingiva and periodontal pocket. Thus, increasing the likelihood of periodontitis and gingivitis caused by COVID-19. The cytokine storm during COVID-19 similarly arises during periodontal inflammation. Studies have reported that NOD-Like Receptor family pyrin domain-containing 3 (NLRP3) inflammasome is significant in the cytokine storm. Recently, the course of the COVID-19 has been related to the melatonin levels in both COVID-19 and periodontal diseases. It is known that melatonin prevents the activation of NLRP3 inflammasome. In light of these findings, we think that melatonin treatment during COVID-19 or periodontal diseases may prevent the damage seen in periodontal tissues by preventing the activation of NLRP3 inflammasome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cholestasis is associated with the accumulation of bile acids and bilirubin in the hepatocytes and leads to liver injury. Pregnane X Receptor (PXR) coordinates protective hepatic responses to toxic stimuli, and this receptor was reported to stimulate bile secretion by increasing MRP2 expression. Since PXR activators were reported to be anti-inflammatory in the liver, PXR was proposed as a drug target for the treatment of chronic inflammatory liver diseases. We investigated the potential protective effect of spironolactone (SPL), an enzyme inducer, in hepatotoxicity induced by bile duct ligation in rats. Wistar Albino (250-300 g) rats were divided into the control group and the bile duct ligated (BDL) group. BDL group was divided into three subgroups; following BDL, for 3 days, the first group received propylene glycol (vehicle of SPL) (blinded), the second subgroup received spironolactone (SPL) (200 mg/kg oral), and the third subgroup received SPL for 3 days, starting 3 days after the bile duct ligation, in order to investigate if it has a healing effect after hepatitis had developed. The control group was sham-operated and received saline. At the end of the experiment, blood and tissue samples were collected. Serum TNF-α, NF-ĸB, bilirubin, IL-6 levels, ALT, AST, ALP activities and tissue MPO activity and oxidant damage increased after the bile duct ligation was significantly decreased following SPL administration. PXR and MRP2 activity showed an increase in the hepatocytes as a result of the treatment. In conclusion, it was observed that SPL administration significantly decreases liver inflammation and damage related to BDL.

Aim: The aim of this study was to investigate the possible therapeutic impacts of two pineal hormones, melatonin and 5-methoxytryptophol (5-MTX), in a rat model of acute pulpitis by analyzing biochemical and histopathological parameters., Methods: This research was done using 32 male and female Wistar albino rats with weight between 200 and 250 g. The rats were randomly divided into four groups: a control group (rats without any treatment), acute pulpitis (AP) group, AP+melatonin group, and AP+5-MTX group. In the AP-induced groups, the crowns of the upper left incisors were removed horizontally. Lipopolysaccharide solution was applied to the exposed pulp tissue before the canal orifices were sealed with a temporary filling material. Melatonin (10 mg/kg) and 5-MTX (5 mg/kg) were administered intraperitoneally. The rats were sacrificed 24 hours after pulp injury, and trunk blood and pulp samples were collected. The concentrations of TNF- α , IL-1 β , MMP-1, and MMP-2 in sera and pulp samples were determined using ELISA assay kits., Results: TNF- α , IL-1 β , MMP-1, and MMP-2 levels in the serum and pulp tissues were considerably higher in the AP group than the control group ( p < 0.01-0.001). In the AP+melatonin and AP+5-MTX groups, TNF- α , IL-1 β , MMP-1, and MMP-2 levels in the serum and pulp tissues were significantly lower than in the AP group ( p < 0.05-0.001)., Conclusions: Both melatonin and 5-MTX provided protective effects on acute pulpitis, which indicates they may be promising as a therapeutic strategy for oral disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Fatma Kermeoğlu et al.)

Declared as a pandemic by the World Health Organization, COVID-19 causes damage to tissues with the cytokine storm. It even causes death in people who are fond of it. In this case, the role of the immune system is vital. In particular, the cycle of melatonin and 5-methoxytryptophol released from the pineal hormone ensures that immunity continues for 24 h. While 5-MTX is active in sunlight, melatonin secretion increases in the dark at night. 5-MTX, like melatonin, has shown antioxidant and immunomodulatory properties in studies. Therefore, people who are sick and those who are not must strictly comply with the 24-h circadian rhythm during this period. We think that it is crucial in terms of being protected from the disease that we should carry out our activities according to the circadian rhythm., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) affects several organs including the kidneys. When examining patients with acute kidney injury (AKI) due to COVID-19, it is important to consider the circadian rhythm because in addition to its biological clock function, disruption of the circadian rhythm has been reported to be associated with the pathogenesis of several disorders, including AKI. Angiotensin-converting enzyme 2 (ACE2), an important component of the renin-angiotensin-aldosterone system (RAAS), displays circadian rhythmicity. Studies have shown that over-expression of human ACE2 increases the replication of SARS-CoV-2, which may lead to disruptions and tissue damage due to the suppression of the brain and muscle ARNT-like protein-1(Bmal1) gene and high pro-inflammatory cytokines expressions in the tissues. Therefore, understanding and regulating the circadian rhythm and expression pattern of the key components of RAAS can prevent or reduce the severity of acute kidney injury that may occur with COVID-19 infection., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks α-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and α-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on α-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and α-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions.

The solute carrier (SLC) superfamily is one of the major sub-groups of membrane proteins in mammalian cells. The solute carrier proteins include more than 400 different membrane-spanning solute carriers organized with 65 families in the human. In solute carrier family neurons, neurotransmitter is considered to be a pharmacological target of neuropsychiatric drugs because of their important role in the recovery of neurotransmitters such as GABA, glutamate, serotonin, dopamine and noradrenaline and regulation of their concentration in synaptic regions. Therefore, solute carrier transporters play vital and different roles in neurodegenerative disorders. In this article, the role of solute carrier transporters in neurodegenerative disorders such as Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Parkinson's diseases, depression, post-traumatic stress disorder, dementia, schizophrenia, and Epilepsy reviewed and discussed to see how defects or absences in SLC transporter cause neurodegenerative disorders. In this review, we try to summarize what is known about solute carriers with respect to brain distribution and expression. The review summarizes current knowledge on the roles of solute carrier transporters in neurodegenerative disorders.

Objectives: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury., Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+-ATPase enzyme activities were analyzed to study tissue injury under light microscope., Results: While IR increased AST, ALT, TNF-α, and IL-1β levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values., Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2019, Turkish Surgical Society.)

Aim: To investigate the possible therapeutic effects of alpha-lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro-CT parameters., Methodology: The study was approved by the Animal Ethics Committee of the Near East University. Thirty-two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4-weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg -1 , for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg -1 , for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro-CT. Groups of data were compared with a two-way analysis of variance (two-way anova) followed by Sidak's multiple comparison tests. Values of P < 0.05 were regarded as significant., Results: TNF-α, IL-1β, MMP-1, MMP-2 levels were significantly lower in AP + ALA group compared with AP group (P < 0.05). There was a significant difference between the AP and AP + ALA groups according to assessment of the inflammatory scores (P < 0.05). The periapical inflammatory infiltrates were significantly more severe (P < 0.05) in the AP group. The AP + ALA group exhibited lower values both in terms of surface area and volume of resorption cavities than the AP group and this difference was significant (P < 0.05)., Conclusion: alpha-lipoic acid treatment provided therapeutic effects on the inhibition of periapical bone loss., (© 2019 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury., Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis., Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1β levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity., Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Background: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma., Methods: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis., Results: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury., Conclusion: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.

Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.

The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a single dose of 20 mg/kg Mtx to group 2 and group 3 at the fifteenth day. The medical ozone preconditioning was administered intraperitonealy in group 3 for fifteen days and more five days after inducing Mtx. The other rats of the group 1 and 2 received saline injection. At the twentyfirst day the blood and the liver tissue samples were obtained to measure the levels of liver enzymes ALT and AST, proinflamatory cytokines TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. And the histolopatological examination was evaluated for injury score. In our study Mtx administration caused a significant increase on the liver enzymes ALT and AST, the tissue MDA and MPO activity and significant decrease in the tissue GSH. Moreover the both pro-inflammatory cytokines were significantly increased in the Mtx group. Medical ozone preconditioning and treatment reversed all these biochemical parameters and histopathological changes of the hepatotoxicity induced by Mtx. We conclude that medical ozone ameliorates Mtx induced hepatotoxicity in rats.

Purpose: To determine the antioxidant and anti-inflammatory effects of alfa lipoic acid (ALA) on the liver injury induced by methotrexate (MTX) in rats., Methods: Thirty two rats were randomly assigned into four equal groups; control, ALA, MTX and MTX with ALA groups. Liver injury was performed with a single dose of MTX (20 mg/kg) to groups 3 and 4. The ALA was administered intraperitonealy for five days in groups 2 and 4. The other rats received saline injection. At the sixth day the rats decapitated, blood and liver tissue samples were removed for TNF-α, IL-1β, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels measurement and histological examination., Results: MTX administration caused a significant decrease in tissue GSH, and tissue Na+, K+ ATPase activity and which was accompanied with significant increases in tissue MDA and MPO activity. Moreover the pro-inflammatory cytokines (TNF-α, IL- β) were significantly increased in the MTX group. On the other hand, ALA treatment reversed all these biochemical indices as well as histopathological alterations induced by MTX., Conclusion: Alfa lipoic acid ameliorates methotrexate induced oxidative damage of liver in rats with its anti-inflammatory and antioxidant effects.

Objective: The purpose of this study is to determine the antioxidant and anti-inflammatory effects of alpha lipoic acid (ALA) on methotrexate (MTX) induced kidney injury in rats., Materials and Methods: Thirty-two rats were equally divided into four groups; control, ALA, MTX and MTX with ALA groups. A single dose of MTX (20 mg/kg) was administered to make kidney injury to groups 3 and 4, intraperitoneally. The ALA was administered intraperitonealy in groups 2 and 4 and the other groups received saline injection for five days. On the sixth day the blood samples and kidney tissues were obtained for the measurement of TNF-α, IL-1β, malondialdehyde, glutathione, myeloperoxidase and sodium potassium-adenosine triphosphatase levels and histological examination., Results: Administration of MTX caused a decrease in tissue GSH, and Na+, K+-ATPase activity significantly. A significant increase in tissue MDA and MPO activities were also seen. The pro-inflammatory cytokines (TNF-α, IL-β) were increased in the MTX group significantly. ALA treatment reversed all biochemical indices as well as histopathological alterations induced by MTX administration., Conclusions: MTX made oxidative damage on kidneys of rat and it was partially prevented by anti-inflammatory and antioxidant effects of ALA treatment.

Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to investigate the antioxidant and anti-inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)-induced hepatorenal oxidative damage in rats., Methods: Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 µmol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium-adenosine triphosphatase (Na(+)/K(+) -ATPase) activity. TNF-α and IL-1β levels were measured in the blood., Key Findings: Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na(+)/K(+) -ATPase activity, while these alterations were reversed in the CAPE-treated MTX group. Elevated TNF-α and IL-1β levels were also reduced with CAPE treatment., Conclusions: The results of this study revealed that CAPE, through its anti-inflammatory and antioxidant actions, alleviates methotrexate-induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Background: The present study aimed to determine the effects of alpha lipoic acid (ALA) on blood and tissue biochemical parameters, as well as tissue histopathology, in an experimental rat model of cerulein-induced acute pancreatitis (AP)., Methods: Three groups consisting of eight rats each were used, as follows: Group 1, controls; Group 2, cerulein-induced pancreatitis group treated with saline; and Group 3, cerulein-induced pancreatitis group treated with ALA. AP was induced by intraperitoneal administration of cerulein (20 µg/kg) 4 times at 1-hour intervals. The animals were decapitated 12 hours after the last dose of cerulein. Blood amylase, lipase, interleukin (IL)-1ß, and tumor necrosis factor (TNF)-α levels, pancreas tissue glutathione (GSH) and malondialdehyde (MDA) levels, as well as myeloperoxidase (MPO) and Na+-K+-ATPase activity were measured. Pancreatic tissue samples were also evaluated histopathologically under a light microscope., Results: While plasma amylase, lipase, IL-1ß, and TNF-α levels, and tissue MDA and MPO levels significantly increased in rats with cerulean-induced AP, tissue GSH and Na+-K+-ATPase activity significantly reduced. These changes were reversed and improved with ALA treatment., Conclusion: Our findings suggest that ALA may significantly reduce morbidity and mortality by preventing organ dysfunction induced by free radicals in the pancreas.