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1.
Biotech Histochem ; 98(6): 424-431, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37291906

ABSTRACT

We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56-100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.


Subject(s)
Polygonum , Stomach Ulcer , Rats , Animals , Indomethacin/toxicity , Antioxidants/pharmacology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Plant Extracts/pharmacology , Rats, Wistar
2.
J Ethnopharmacol ; 287: 114843, 2022 Apr 06.
Article in English | MEDLINE | ID: mdl-34801610

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Okra fruit (Abelmoschus esculentus (L.) Moench) has been extensively used for the treatment of skin damage and subcutaneous tissue abscess for many years in Turkish folk medicine. AIM OF STUDY: In this study, we aimed to investigate the wound healing potential of okra fruit by in vitro and in vivo experimental models in detail. Furthermore, based on the results of experiments, a wound healing formulation was developed and its activity profile was studied. MATERIALS AND METHODS: For this purpose, the phenolic, flavonoid and proanthocyanidin contents and chemical profile of aqueous and ethanolic extracts prepared from okra fruits cultivated in two different locations of Turkey, i.e. Aegean and Kilis regions, were comparatively determined and the tryptophan levels, which is known to be an influential factor in wound healing, were measured. Antioxidant activity of the okra fruit extracts was determined by DPPH test, ABTS radical scavenger activity, iron-binding capacity, total antioxidant capacity and copper reduction capacity assays. Moreover, antibacterial activity potentials of the aqueous and ethanolic extracts of okra fruits were determined. The protective effect of the extracts against H2O2-induced oxidative stress and anti-inflammatory activity were assessed in HDF (human dermal fibroblast) cells and in RAW 264.7 murine macrophages, respectively. The biocompatibility of the gel formulations prepared with the best performing extract were evaluated by human Epiderm™ reconstituted skin irritation test model. Wound-healing activity was investigated in rats by in vivo excision model and, histopathological examination of tissues and gene expression levels of inflammation markers were also determined. RESULTS: According to our findings, the aqueous and ethanolic extracts of okra fruits were found to possess a rich in phenolic content. Besides, isoquercitrin was found to be a marker component in ethanolic extracts of okra fruits. Both extracts exhibited antioxidant activity with significant protective effect against H2O2-induced damage in HDF cells by diminishing the MDA level. Also, the highest dose of ethanolic extracts has displayed a potent anti-inflammatory activity on LPS-induced RAW264.7 cells. Besides, both water and ethanolic extracts were shown to possess antimicrobial activity. On the other hand, the formulations prepared from the extracts were found non-irritant on in vitro Epiderm™-SIT. In vivo excision assay showed that tissue TGF-ß and IL-1ß levels were significantly decreased by the 5% okra ethanolic gel formulation. The histopathological analysis also demonstrated that collagenisation and granulation tissue maturation were found higher in 5% (w/v) okra ethanolic extract-treated group. CONCLUSION: 5% of okra ethanolic extract might be suggested as a potent wound healing agent based on the antimicrobial, antioxidant and anti-inflammatory tests. The proposed activity was also confirmed by the histopathological findings and gene expression analysis.


Subject(s)
Abelmoschus/chemistry , Antioxidants/pharmacology , Plant Extracts/pharmacology , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antioxidants/isolation & purification , Cells, Cultured , Fibroblasts/drug effects , Fruit , Humans , Hydrogen Peroxide , Macrophages/drug effects , Macrophages/pathology , Male , Medicine, Traditional , Mice , Oxidative Stress/drug effects , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Turkey
3.
Amino Acids ; 53(10): 1569-1588, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34605988

ABSTRACT

The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC-MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.


Subject(s)
Amino Acids/blood , COVID-19/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , Chromatography, Liquid , Female , Humans , Male , Mass Spectrometry , Middle Aged , Prognosis
4.
Bioorg Chem ; 105: 104435, 2020 12.
Article in English | MEDLINE | ID: mdl-33161254

ABSTRACT

This study aims to determine whether atomoxetine (ATX), used as an alternative to methylphenidate, affects superoxide dismutase (SOD) activity besides glutathione (GSH) and malondialdehyde (MDA) levels, apart from determining possible effects of ATX on SOD activity through molecular docking studies. 24 male Wistar rats were divided into 4 groups, each containing 6 members. After a 6-week application of ATX, blood samples and brain tissues were obtained from the rats for biochemical analyses. Besides, molecular docking studies were conducted using PyRx and Discovery Studio 3.0 programs. No significant difference occurred in GSH and MDA levels after ATX application. A high-dose application of ATX caused a statistically significant change only in the serum-SOD activity compared to that of Control Group. Molecular docking studies revealed that ATX settled in the biggest space rather than the catalytic regions of Cu2Zn2-SOD. Our biochemical and molecular docking data showed that ATX, an alternative drug to stimulant methylphenidate, showed no significant changes in the antioxidant defence system at either low or therapeutic doses after long-term use. Therefore, we suggest ATX could be used as a substitute for methylphenidate in the long-term treatment of ADHD.


Subject(s)
Atomoxetine Hydrochloride/pharmacology , Attention Deficit Disorder with Hyperactivity/drug therapy , Molecular Docking Simulation , Superoxide Dismutase/metabolism , Administration, Oral , Animals , Atomoxetine Hydrochloride/administration & dosage , Attention Deficit Disorder with Hyperactivity/metabolism , Brain/drug effects , Brain/enzymology , Dose-Response Relationship, Drug , Male , Molecular Structure , Rats , Rats, Wistar , Structure-Activity Relationship , Superoxide Dismutase/blood
5.
Ren Fail ; 39(1): 314-322, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28100100

ABSTRACT

Contrast media (CM) is known to have nephrotoxic adverse effects. Epigallocatechin-3-gallate (EGCG) is the most abundant and active catechin in green tea, and has strong antioxidant and anti-inflammatory properties. This study investigated whether EGCG can reduce contrast-induced nephrotoxicity (CIN), alone or with glycerol (GLY)-induced renal damage, and to understand its mechanisms of protection against toxicity, using models of GLY and CIN in rats. The rats were separated into eight groups (n = 6 in each), as follows: Healthy, GLY, CM, GLY + CM, CM + EGCG 50 mg/kg (po), GLY + CM + EGCG 50 mg/kg (po), CM + EGCG 100 mg/kg (po), and GLY + CM + EGCG 100 mg/kg (po). Both doses of EGCG protected against CM-induced renal dysfunction, as measured by serum creatinine and blood urea nitrogen (BUN). In addition, EGCG treatment markedly improved CIN-induced oxidative stress, and resulted in a significant down-regulatory effect on tumor necrosis factor (TNF)-α and nuclear factor (NF)-κB mRNA expression. Moreover, histopathological analysis showed that EGCG also attenuated CM-induced kidney damage. Considering the potential clinical use of CM and the numerous health benefits of EGCG, this study showed the protective role of multi-dose EGCG treatment on CIN and GLY-aggravated CIN through different mechanisms.


Subject(s)
Antioxidants/pharmacology , Catechin/analogs & derivatives , Contrast Media/adverse effects , Glycerol/adverse effects , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Animals , Blood Urea Nitrogen , Catechin/pharmacology , Cytokines/blood , Kidney/pathology , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Tea
6.
Ostomy Wound Manage ; 62(3): 26-34, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26978857

ABSTRACT

Argan oil, produced from the kernels of the argan tree (Argania spinosa), has been shown to have antioxidant properties. To examine the effect of argan oil in second-degree burn wound healing, an in vivo experiment was conducted among 30 adult male Wistar rats divided into 5 equal groups: a sham group, a control group (burned but no topical agent), a group in which argan oil was applied once a day, a group in which argan oil was applied twice a day, and a group treated with 1% silver sulfadiazine once a day. Second-degree burns were created by scalding hot water (85˚ C for 15 seconds). Treatment began 24 hours after the burn injury; in the argan oil groups, 1 mL of argan oil was administered via syringe to the wound. The rate of wound healing was quantified by wound measurements on days 1, 7, and 14 after burn injury. Tissues were analyzed for molecular and histologic changes in TGF-ß expression and fibroblast activity. Percent contraction of burned skin tissue was determined using the stereo investigator program, which calculated the burn field to the millimeter. Means (SD) were calculated and compared using Duncan's multiple comparison test. The group receiving argan oil twice daily showed significantly increased mRNA levels of TGF-ß1 from 39.66- to 58.70-fold compared to the burn control group on day 14 (P less than 0.05). Both argan oil-treated groups showed significantly increased contraction compared to the burn control group at all 3 timepoints; the group receiving argan oil twice daily had a greater contraction rate (31% on day 7, 76% on day 14) than the silver sulfadiazine group (22% on day 7, 69% on day 14), (P less than 0.05). Histopathological assessments on days 3, 7, and 14 showed greater healing/contraction in both argan oil and silver sulfadiazine groups compared to the control group. These results suggest argan oil is effective in healing experimentally created second-degree burns in rats. Prospective, randomized, controlled clinical studies are needed to evaluate the safety, efficacy, and effectiveness of this treatment modality for patients with second-degree burn wounds.


Subject(s)
Burns/drug therapy , Phytotherapy , Plant Oils/therapeutic use , Wound Healing , Animals , Burns/pathology , Male , Rats , Rats, Wistar
7.
Pharm Biol ; 54(10): 2082-91, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26956915

ABSTRACT

Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation. Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats. Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later. Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage. Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.


Subject(s)
Acetaminophen , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Kidney Diseases/prevention & control , Kidney/drug effects , Nigella sativa , Plant Extracts/pharmacology , Acetylcysteine/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Biomarkers/blood , Creatinine/blood , Cytoprotection , Disease Models, Animal , Ethanol/chemistry , Female , Glutathione/metabolism , Kidney/metabolism , Kidney/pathology , Kidney Diseases/blood , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Malondialdehyde/metabolism , Nigella sativa/chemistry , Phytotherapy , Plant Extracts/isolation & purification , Plants, Medicinal , Rats, Wistar , Seeds , Solvents/chemistry , Superoxide Dismutase/metabolism , Urea/blood
8.
J Cell Biochem ; 117(2): 308-19, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25941092

ABSTRACT

N-acetyl cysteine (NAC), a metabolite of sulphur-containing amino acid cysteine, is used as an antioxidant and a mucolytic agent. Therefore, we aimed to investigate anti-inflammatory and anti-ulcerative effects of NAC. We also intended to determine the relation between antiulcer effect of NAC and its antioxidant properties by biochemical evaluation. In this study a total of 15 rat groups (n = 6 per group) were used for inflammation and ulcer experiments. Anti-inflammatory effects of NAC have been investigated on six rat groups with carrageenan (CAR)-induced paw oedema model. Antiulcer effects of NAC have been investigated on 24 h fasted nine rat groups with IND-induced ulcer model in the presence of positive (LAN, RAN, FAM, and OMEP), negative (untreated IND group) and intact control groups. In biochemical analyses of stomach tissues; glutathione S-transferase (GST), catalase (CAT), myeloperoxidase (MPO), and superoxide dismutase (SOD) enzyme activities and lipid peroxidation (LPO) and the glutathione (GSH) levels were determined. All doses of NAC exerted significant anti-inflammatory effect; even the effect of 900 mg/kg NAC was similar with that of DIC and IND. In gastric tissues NAC administration decreased the level of LPO and activity of CAT, which were increased by IND. Furthermore, NAC increased the GSH level and SOD and GST activities, which decreased in ulcerous stomach tissues. Only MPO activity increased in both IND and NAC groups when compared to healthy rat group. We determined that NAC has both anti-inflammatory and anti-ulcerative effects.


Subject(s)
Acetylcysteine/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Stomach Ulcer/drug therapy , Acetylcysteine/therapeutic use , Animals , Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Carrageenan , Catalase/metabolism , Drug Evaluation, Preclinical , Edema/chemically induced , Edema/drug therapy , Edema/metabolism , Glutathione Transferase/metabolism , Indomethacin , Lipid Peroxidation , Oxidative Stress , Peroxidase/metabolism , Rats, Wistar , Stomach/drug effects , Stomach/enzymology , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Superoxide Dismutase/metabolism
9.
Naunyn Schmiedebergs Arch Pharmacol ; 387(11): 1025-36, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25038619

ABSTRACT

This study investigated the fracture-healing effects of α-lipoic acid (α-LA), which was applied orally once daily in preventive treatment mode during 1 month after fracture induction. Rats were randomly divided into sham-operated group (group 1), femoral fracture control (group 2), femoral fracture + 25 mg/kg α-LA (group 3), and femoral fracture + 50 mg/kg α-LA (group 4). Rats in the experimental groups were orally administered 25 or 50 mg/kg α-LA once daily for 30 days starting from postoperative day 1. Thirty days postoperatively, the rats underwent X-ray imaging and were then euthanized for blood and tissue collection. Histopathological, biochemical, molecular, computed tomography (CT), and mechanical strength tests were performed on samples. The serum levels of osteocalcin (OC), osteopontin (OP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) did not differ significantly between groups 2 and 3. Serum OC, OP, TNF-α, and IL-6 levels in group 4 were significantly lower than those in group 3. From X-ray images, staging for fracture healing was scored as <2 in group 2, >2 in group 3, and >3 in group 4. In group 2, the average score of less than 2 suggests insufficient fracture healing; those of both the α-LA groups were >2, indicating progression of healing. Transforming growth factor beta (TGF-ß) messenger RNA (mRNA) levels were significantly higher in the sham group than in the femoral fracture control. Both doses of α-LA increased TGF-ß mRNA expression compared to the fracture group. CT results and biomechanical testing at 4 week after fracture demonstrated that α-LA has fastened bone healing, which was confirmed by stereological analyses in which 50 mg/kg α-LA increased the number of osteoclasts. Our findings indicate that α-LA supplementation promotes healing of femoral fractures in rats.


Subject(s)
Femoral Fractures/drug therapy , Fracture Healing/drug effects , Thioctic Acid/pharmacology , Administration, Oral , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Gene Expression Regulation , RNA, Messenger/metabolism , Rats , Rats, Wistar , Thioctic Acid/administration & dosage , Tomography, X-Ray Computed , Transforming Growth Factor beta/genetics , Treatment Outcome
10.
Eur J Pharmacol ; 674(2-3): 171-8, 2012 Jan 15.
Article in English | MEDLINE | ID: mdl-22119377

ABSTRACT

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.


Subject(s)
Anisoles/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Hydroxybenzoates/pharmacology , Plant Oils/pharmacology , Prostheses and Implants/adverse effects , Titanium/adverse effects , Animals , Caspases/metabolism , Cell Count , Glutathione/metabolism , Male , Nitric Oxide Synthase Type II/metabolism , Olive Oil , Oxidative Stress/drug effects , Peroxidase/metabolism , Rabbits , Superoxide Dismutase/metabolism
11.
J Ethnopharmacol ; 138(2): 408-14, 2011 Nov 18.
Article in English | MEDLINE | ID: mdl-21963562

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. MATERIALS AND METHODS: The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. RESULTS: The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. CONCLUSION: More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment.


Subject(s)
Helichrysum/chemistry , Plant Extracts/pharmacology , Urolithiasis/prevention & control , Animals , Body Weight , Disease Models, Animal , Hydrogen-Ion Concentration , Male , Rats , Rats, Sprague-Dawley , Urolithiasis/blood , Urolithiasis/urine
12.
Turk Neurosurg ; 21(2): 191-6, 2011.
Article in English | MEDLINE | ID: mdl-21534201

ABSTRACT

AIM: The aim of this study was to investigate the effects of impulse noise on the epithelial cells of the choroid plexus. MATERIAL AND METHODS: Forty Sprague Dawley rats were used and divided into the 2 groups as control and study groups. In the control group, the rats did not suffer noise injury. The rats were exposed to impulse noise at 20 minute durations at 10 times each day for one month in study group. Then, the rats were sacrificed and the choroid plexuses were examined histologically. The number of cells was counted and the cells were analyzed. RESULTS: There were clear signs of nuclear condensation and cell body shrinkage, suggesting the presence of apoptosis. Severe desquamation of villus and the cell loss were observed in the study group. The numbers of the normal cells decreased, and the number of apoptotic cells increased significantly (p < 0.05). CONCLUSION: Impulse noise causes apoptotic death of epithelial cells in the choroid plexus, decrease the normal cells and increase the apoptotic cells.


Subject(s)
Choroid Plexus/injuries , Choroid Plexus/pathology , Epithelial Cells/pathology , Noise/adverse effects , Acoustic Stimulation/methods , Animals , Apoptosis , Atrophy , Cell Count , Female , Male , Microvilli/pathology , Music , Rats , Rats, Sprague-Dawley
13.
Biochem Biophys Res Commun ; 408(3): 454-8, 2011 May 13.
Article in English | MEDLINE | ID: mdl-21527245

ABSTRACT

Aging is associated with oxidative damage and an imbalance in redox signaling in a variety of tissues, yet little is known about the extent of age-induced oxidative stress in the sympathoadrenal system. Lifelong caloric restriction has been shown to lower levels of oxidative stress and slow the aging process. Therefore, the aims of this study were twofold: (1) to investigate the effect of aging on oxidative stress in the adrenal medulla and hypothalamus and (2) determine if lifelong 40% caloric restriction (CR) reverses the adverse effects of age-induced oxidative stress in the sympathetic adrenomedullary system. Adult (18months) and very old (38months) male Fischer 344 x Brown Norway rats were divided into ad libitum or 40% CR groups and parameters of oxidative stress were analyzed in the adrenal medulla and the hypothalamus. A significant age-dependent increase in lipid peroxidation (+20%, P<0.05) and tyrosine nitration (+111%, P<0.001) were observed in the adrenal medulla while age resulted in a reduction in the protein expression of key antioxidant enzymes, CuZnSOD (-27%, P<0.01) and catalase (-27%, P<0.05) in the hypothalamus. Lifelong CR completely prevented the age-induced increase in lipid peroxidation in the adrenal medulla and restored the age-related decline in antioxidant enzymes in the hypothalamus. These data indicate that aging results in a significant increase in oxidative stress in the sympathoadrenal system. Importantly, lifelong CR restored the age-related changes in oxidative stress in the adrenal medulla and hypothalamus. Caloric restriction could be a potential non-pharmacological intervention to prevent increased oxidative stress in the sympathetic adrenomedullary system with age.


Subject(s)
Adrenal Medulla/physiology , Aging/physiology , Caloric Restriction , Hypothalamus/physiology , Oxidative Stress , Sympathetic Nervous System/physiology , Adrenal Medulla/enzymology , Age Factors , Aldehydes/metabolism , Animals , Body Weight , Hypothalamus/enzymology , Rats , Rats, Inbred BN , Rats, Inbred F344 , Superoxide Dismutase/biosynthesis
14.
J Nat Med ; 64(1): 42-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19830512

ABSTRACT

The anti-inflammatory effects of the methanol extract of the lichen species Peltigera rufescens (Weis.) Humb (MEPR) (Peltigeraceae) on acute (carrageenan-induced) and chronic (cotton pellet granule) phases of inflammation were investigated. The MEPR was capable of reducing carrageenan-induced inflammation and showed a potent antiproliferative effect (63.5%) in the chronic inflammation model. Inflammation is related to neutrophil infiltration and the production of neutrophil-derived mediators and free radicals. The MEPR reduced the myeloperoxidase and inducible nitric oxide synthase (NOS) activities, which were increased by carrageenan injection. Carrageenan injection also increased the lipid peroxidation (LPO) as compared with untreated paw tissues. The administration of MEPR, diclofenac, and indomethacin reduced the LPO in paw tissues through amelioration of the antioxidant defense systems. Neutrophil infiltration and neutrophil-derived free radicals in tissues therefore appeared to play an important role in the inflammation process induced by carrageenan. The anti-inflammatory effect of MEPR could be attributed to its reducing effect on the neutrophil-derived free radicals and its ameliorating effect on the antioxidant defense systems.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Lichens/chemistry , Plant Extracts/pharmacology , Acute Disease , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/pharmacology , Carrageenan , Chronic Disease , Diclofenac/pharmacology , Disease Models, Animal , Indomethacin/pharmacology , Inflammation/physiopathology , Lipid Peroxidation/drug effects , Male , Neutrophil Infiltration/drug effects , Rats , Rats, Sprague-Dawley
15.
Phytother Res ; 23(5): 635-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19107853

ABSTRACT

Lobaria pulmonaria, a lichen species, has been used in traditional medicine for the treatment of various diseases. This study was designed to determine the gastroprotective effect of the methanol extract of L. pulmonaria in an indometacin-induced ulcer model in rats. The results showed that gastric lesions were significantly reduced in a dose-dependent manner. Furthermore, the administration of indometacin caused a significant decrease in the levels of superoxide, glutathione peroxidase and reduced glutathione and an increase in the lipid peroxidation level. Administration of the lichen extract, however, produced an increase in the levels of these enzymes and a decrease in lipid peroxidation levels, although catalase and myeloperoxidase levels were unaffected. The present results suggested that Lobaria pulmonaria has a gastroprotective effect, probably due to reducing oxidative stress and neutrophil infiltration.


Subject(s)
Gastric Mucosa/drug effects , Indomethacin/adverse effects , Lichens/chemistry , Neutrophil Infiltration/drug effects , Oxidative Stress/drug effects , Stomach Ulcer/drug therapy , Animals , Catalase/metabolism , Dose-Response Relationship, Drug , Gastric Mucosa/pathology , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Rats , Rats, Wistar , Superoxide Dismutase/metabolism
16.
Eur J Pharmacol ; 591(1-3): 300-6, 2008 Sep 04.
Article in English | MEDLINE | ID: mdl-18621042

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are widely used in the treatment of inflammation, fever and pain. However, NSAIDs cause gastric damage as a major adverse reaction. In this study, the effects of vegetable oils (corn, olive and sunflower oils) and alpha-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin were evaluated in rats. Results showed that indomethacin given with sunflower, corn and olive oils reduced paw edema induced by carrageenan by 79.5%, 74.0% and 60.5%, whereas individual indomethacin and diclofenac reduced paw edema by 56.2% and 50.7%, respectively. Furthermore, it has been found that the vegetable oils possess significant anti-inflammatory effect against paw edema when given alone. These results showed that the vegetable oils have beneficial effects on reduction paw edema induced by carrageenan. Besides, the administration of indomethacin together with the vegetable oils and alpha-tocopherol did not cause a statistically significant gastric damage in rats (P>0.05). However, indomethacin caused statistically significant gastric lesions as compared with untreated rats (P<0.05). Moreover, it was also found that the effects of the vegetable oils and alpha-tocopherol improved the levels of antioxidant defense systems in rat stomach tissues against oxidative damage. These results suggest that indomethacin as well as other NSAIDs do not have any adverse effect on the gastrointestinal tract when they are used together with vegetable oils and vitamin E or as the preparations of the oils.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Indomethacin/pharmacology , Inflammation/drug therapy , Plant Oils/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antioxidants/pharmacology , Corn Oil/pharmacology , Indomethacin/adverse effects , Male , Olive Oil , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Stomach Ulcer/prevention & control , Sunflower Oil , alpha-Tocopherol/pharmacology
17.
Eur J Pharmacol ; 579(1-3): 241-5, 2008 Jan 28.
Article in English | MEDLINE | ID: mdl-17936271

ABSTRACT

Bone is a dynamic organ system that is directly related to calcium and phosphor metabolism. Imbalance in these two parameters upon aging or menopause leads to osteoporosis. Recently, it was also shown by researchers that high blood pressure in elderly women is statistically associated with decreased bone mineral content at the femoral neck, which may increase the susceptibility to fractures. The aim of our study was to investigate the effects of different doses of amlodipine and lacidipine on ovariectomized rat femurs' calcium and phosphor content. Bone calcium and phosphor concentration was measured by a Wavelength Dispersive Spectrometer. Calcium contents of the rat femurs were significantly lower in the ovariectomized group than in the sham group eight weeks after the operation. Amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats, compared to those of control (ovariectomized) group. Both doses of lacidipine (1 and 3 mg/kg) also effectively increased calcium concentrations (P<0.01) significantly in ovariectomized rats. On the other hand amlodipine treatment at doses of 1 and 3 mg/kg significantly increased the calcium (P<0.01) and phosphor concentrations (P<0.01) in the femurs of ovariectomized rats compared with those of the sham group. In conclusion, amlodipine and lacidipine improved the bone loss in an ovariectomy induced osteopenic rat model. Our findings suggest that potent calcium channel blockers such as amlodipine and lacidipine have a beneficial effect on bone metabolism, and an antihypertensive effect.


Subject(s)
Amlodipine/pharmacology , Calcium Channel Blockers/pharmacology , Dihydropyridines/pharmacology , Osteoporosis/drug therapy , Amlodipine/administration & dosage , Animals , Bone and Bones/drug effects , Bone and Bones/physiopathology , Calcium/metabolism , Dihydropyridines/administration & dosage , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Femur/drug effects , Femur/pathology , Ovariectomy , Phosphorus/metabolism , Rats , Rats, Wistar , Spectrometry, X-Ray Emission
18.
Chem Biol Interact ; 170(1): 40-8, 2007 Oct 20.
Article in English | MEDLINE | ID: mdl-17681286

ABSTRACT

This study investigated the effects of Onosma armeniacum K. (Boraginaceae) root extract (AR-1) on ethanol-induced stomach ulcers, and on some oxidant and antioxidant parameters, in stomach tissue in rats. The results obtained showed that AR-1 significantly inhibited ethanol-induced ulcers at 25, 50, 100 and 200 mg/kg doses. We found that 50, 100 and 200 mg/kg doses of AR-1 inhibited ulcers more effectively than did ranitidine. AR-1 at doses of 25, 50, 100 and 200 mg/kg significantly prevented the decrease in total glutathione (tGSH) level which occurs in damaged stomach tissues of rats given ethanol (control group). Only a 100 mg/kg dose of AR-1 significantly increased the glutathione S-transferase (GST) level in stomach tissue compared to the control. All doses of AR-1 except the 25 mg/kg dose eliminated the decrease in the superoxide dismutase (SOD) level in the stomach tissue of rats given ethanol. While all doses of AR-1 decreased malondialdehyde (MDA) levels significantly; all doses AR-1 except 25 mg/kg decreased myeloperoxidase (MPO) levels significantly compared to the control. The effect of AR-1 on catalase (CAT) activity was insignificant at all doses. AR-1 significantly increased nitric oxide (NO) levels at 50, 100 and 200 mg/kg doses compared to the control. Our results indicate that the protection of some antioxidant mechanisms and the inhibition of some oxidant mechanisms have a role in AR-1's antiulcer effect mechanism.


Subject(s)
Boraginaceae/chemistry , Phytotherapy/methods , Plant Extracts/pharmacology , Stomach Ulcer/drug therapy , Stomach/drug effects , Animals , Catalase/metabolism , Ethanol/toxicity , Gastric Mucosa/metabolism , Glutathione/metabolism , Glutathione Transferase/metabolism , Linoleic Acid/metabolism , Lipid Peroxidation/drug effects , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Peroxidase/metabolism , Plant Roots/metabolism , Ranitidine/pharmacology , Rats , Rats, Wistar , Stomach/enzymology , Stomach Ulcer/chemically induced , Stomach Ulcer/enzymology , Stomach Ulcer/metabolism , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism
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