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1.
Neurochem Res ; 45(2): 295-309, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31768814

RESUMO

This study investigated the protective effect of Kaempferol against CdCl2-induced hippocampal damage and memory deficit in rats and investigated if such effects involve modulating the activity of AMPK/PTEN/Akt/mTOR axis. Adult male rats (n = 12/group) were divided into control or CdCl2-treated rats received the vehicle of Kaempferol for consecutive 6 weeks. Also, hippocampal cells were treated with CdCl2 in the presence or absence of Kaempferol for 24 h with or without 1 h pre-incubation with compound C, an AMPK inhibitor or with bpV a PTEN inhibitor. Kaempferol improved the behavioral of CdCl2-treated rats, preserved hippocampus structure and reduced hippocampal levels of ROS and protein levels of Bax and cleaved caspase-3. In both control and CdCl2-treated rats, Kaempferol significantly increased hippocampal levels of GSH levels and protein levels of Nfr2, Bcl2 and synaptic proteins (SNAP-25, PSD-25, and synapsin). Concomitantly, it increased the activity of PTEN and AMPK and subsequently, decreased the activity of Akt and mTOR. In cultured cells, individual pharmacological inhibition of PTEN by bpv or AMPK of compound C (CC) partially prevented the stimulatory effect of Kaempferol on Akt/mTOR and its inhibitory effect on cell death whereas a combination of both inhibitors completely prevented this. Also, inhibition of PTEN alone completely abolished the inhibitory effect of Kaempferol by synaptic proteins, whereas inhibition of AMPK completely abolished its stimulatory effect of Nfr2. In conclusion, Kaempferol protects against CdCl2-induced memory deficits and hippocampal apoptosis by its antioxidant potential and inhibition of Akt/mTOR axis and requires the activation of PTEN and AMPK.


Assuntos
Apoptose/efeitos dos fármacos , Glutationa/metabolismo , Quempferóis/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/uso terapêutico , Peso Corporal/efeitos dos fármacos , Cloreto de Cádmio , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Masculino , Transtornos da Memória/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
2.
Clin Exp Pharmacol Physiol ; 47(7): 1240-1253, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32149419

RESUMO

Exendin-4, a glucagon-like peptide-1 receptor agonist, was shown to protect against cardiac ischaemia/reperfusion (I/R) injury by suppressing oxidative stress. p66 Shc, a pro-oxidant and an apoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin-4 against I/R injury in rats involves inhibition of p66 Shc and to determine the underlying mechanisms behind this. Adult male rats (n = 12/group) were divided into four groups as a sham, a sham + Exendin-4, an I/R, and an I/R + Exendin-4. Exendin-4 was administered to rats 7 days before the induction of I/R. Ischaemia was induced by ligating the left anterior descending (LAD) coronary artery for 40 minutes followed by reperfusion for 10 minutes. The infarct myocardium was used for further analysis. Exendin-4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK-MB in I/R-induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome-c and cleaved caspase-3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti-apoptotic effects. Furthermore, it inhibited JNK and p66 Shc activation and downregulated protein levels of p66 Shc and NADPH oxidase with no effect on protein levels/activity of p53 and PKCßII. Of note, Exendin-4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin-4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P66 Shc/NADPH oxidase.


Assuntos
Antioxidantes/metabolismo , Exenatida/farmacologia , MAP Quinase Quinase 4/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , NADP/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Animais , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
3.
Clin Exp Pharmacol Physiol ; 46(12): 1111-1123, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31398260

RESUMO

This study investigates the effect of chronic consumption of a high-fat diet rich in corn oil (CO-HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)-induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet (STD) (3.82 kcal/g, 9.4% fat), CO-HFD (5.4 kcal/g, 40% fat), T1DM fed STD, and T1DM + CO-HFD. CO-HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase-3, and ANF and decreased levels of Bcl-2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO-HFD. In conclusion, chronic consumption of CO-HFD by T1DM-induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria-mediated cell death.


Assuntos
Morte Celular/efeitos dos fármacos , Óleo de Milho/efeitos adversos , Diabetes Mellitus Tipo 1/patologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/ultraestrutura , Animais , Antioxidantes/metabolismo , Óleo de Milho/administração & dosagem , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Comportamento Alimentar/fisiologia , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Hemodinâmica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
4.
Saudi Dent J ; 36(5): 718-721, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38766296

RESUMO

Objective: This study assessed the demographic characteristics of the periodontal workforce in Saudi Arabia. Methods: This was a retrospective study of periodontists practicing in Saudi Arabia from January 2000 through May 2023. The data were requested from the Saudi Commission for Health Specialties and included the number of periodontists and dentists, the number of Saudi and non-Saudi periodontists, the sex distribution of periodontists, their ranking, and the geographic distribution across the 13 regions. Results: This study identified 700 practicing periodontists, representing 2.2 periodontists per 100,000 people. Consultant periodontists composed 31% of the population, mostly Saudi nationals. Approximately 53% of practicing periodontists resided in Saudi Arabia, mostly in the Riyadh, Makkah, and Eastern Provinces. Al Bahah, Najran, and the Northern Borders had fewer periodontists. Conclusion: This study provides valuable insights into shaping the periodontal workforce in Saudi Arabia. Future studies on the factors related to the periodontology workforce can assist policymakers in implementing effective strategies to significantly improve the current workforce.

5.
Int Dent J ; 73(2): 267-273, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35803777

RESUMO

OBJECTIVE: There are no studies that have evaluated the effect of Alveogyl with and without adjunct photobiomodulation therapy (PBMT) in reducing self-rated post-operative pain (SPP) in patients with alveolar osteitis (AO; dry socket). The aim of the present randomised controlled trial was to assess the effectiveness of Alveogyl with and without PBMT for the management of SPP in patients with AO. METHODS: Adult nonsmokers with diagnosed AO were included. Patients were randomly divided into 4 groups. In Group 1, patients underwent mechanical curettage (MC) with copious normal saline irrigation. In Group 2, patients underwent MC + Alveogyl dressings in extraction sites which were changed every 48 hours until cessation of pain. In Group 3, patients underwent MC + Alveogyl followed by PBMT using a 660-nm indium-gallium-aluminum-phosphide diode laser. In Group 4, patients were treated solely with PBMT. The visual analogue scale was used up to 3 postoperative days to assess SPP up to 3 days at 6- (T0) and 12-hour (T1) intervals. Statistical analyses were performed using the analysis of variance and Bonferroni post hoc adjustment tests. Correlation between SPP scores and age, sex, and eruption status of teeth was assessed using logistic regression models. P values <.01 were nominated as being statistically significant. RESULTS: In all, 14, 13, 14, and 14 individuals with AO were included in groups 1, 2, 3 and 4, respectively. All patients had undergone extraction of mandibular third molars. At baseline and on day 1, there was no difference in SPP in all groups. On days 2 and 3, mean visual analogue scale (VAS) scores at T1 (P < .01) and T2 (P < .01) intervals were significantly high in Group 2 compared with Group 3. On days 2 and 3, mean VAS scores at T1 (P < .01) and T2 (P < .01) intervals were significantly high in Group 4 compared with Group 3. There was no difference in SPP in groups 3 and 4 on day 3 at T0 and T1 intervals. CONCLUSIONS: PBMT following MC and Alveogyl dressing is more efficient in reducing SPP compared with MC with or without Alveogyl dressing in patients with AO.


Assuntos
Alvéolo Seco , Adulto , Humanos , Alvéolo Seco/etiologia , Extração Dentária , Dente Molar , Medição da Dor
6.
Aging (Albany NY) ; 13(24): 25607-25642, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34968192

RESUMO

Aging is accompanied by osteopenia, characterized by reduced bone formation and increased bone resorption. Osteocytes, the terminally differentiated osteoblasts, are regulators of bone homeostasis, and parathyroid hormone (PTH) receptor (PPR) signaling in mature osteoblasts/osteocytes is essential for PTH-driven anabolic and catabolic skeletal responses. However, the role of PPR signaling in those cells during aging has not been investigated. The aim of this study was to analyze the role of PTH signaling in mature osteoblasts/osteocytes during aging. Mice lacking PPR in osteocyte (Dmp1-PPRKO) display an age-dependent osteopenia characterized by a significant decrease in osteoblast activity and increase in osteoclast number and activity. At the molecular level, the absence of PPR signaling in mature osteoblasts/osteocytes is associated with an increase in serum sclerostin and a significant increase in osteocytes expressing 4-hydroxy-2-nonenals, a marker of oxidative stress. In Dmp1-PPRKO mice there was an age-dependent increase in p16Ink4a/Cdkn2a expression, whereas it was unchanged in controls. In vitro studies demonstrated that PTH protects osteocytes from oxidative stress-induced cell death. In summary, we reported that PPR signaling in osteocytes is important for protecting the skeleton from age-induced bone loss by restraining osteoclast's activity and protecting osteocytes from oxidative stresses.


Assuntos
Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteócitos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Receptor Tipo 1 de Hormônio Paratireóideo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Doenças Ósseas Metabólicas/patologia , Reabsorção Óssea/metabolismo , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Homeostase/efeitos dos fármacos , Camundongos , Camundongos Knockout , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteócitos/metabolismo , Osteoporose/metabolismo
7.
Saudi Dent J ; 26(3): 88-95, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25057228

RESUMO

OBJECTIVE: To assess smoking prevalence among dental students at King Saud University (KSU) and to determine possible risk factors of tobacco use. METHODS: A self-addressed invitation letter was sent to all dental students (males and females) at KSU requesting participation in this study. Data on smoking habits, associated risk factors, and demographic factors, such as age, marital status, residency status, the student's year of study, and grade point average, were collected by an electronic self-administered questionnaire sent via email. Data were analyzed using SPSS. Significant differences between different groups were assessed with a Pearson Chi-Square test at α = 0.05. Logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) and to determine the effect of different risk factors on students' smoking habits. RESULTS: Of the 600 registered dental students, 400 students responded (230 males, 170 females), representing a response rate of 67%. More male than female students were current smokers (27.6% vs. 2.4%, p < 0.001). Most smokers used shisha tobacco only (N = 35, 51.5%), followed by both shisha tobacco and cigarettes (N = 17, 25%), or cigarettes only (N = 16, 23.5%). Male students were about 4 times more likely to be smokers if all or most of their friends were smokers compared to students who had some friends who smoked (OR = 3.9, 95% CI = 1.9-7.7). A high proportion of current smokers (47.8%) reported stress as the main reason for smoking. Twenty-six percent of dental students (N = 87) who are currently nonsmokers reported that they have used tobacco at some point in their lives. Over two thirds of sampled students (63%) believed that public tobacco usage is not well addressed in the current college curriculum. CONCLUSION: Approximately one in every four male dental students at KSU is a smoker. Having friends who are smokers was the most important risk factor associated with smoking. There is a general belief among dental students that public tobacco use is not well addressed in the dental college curriculum.

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