Comparing the effects of Portulaca oleracea seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress parameters and cardiac hypertrophy in thyrotoxic rats

Pakdel R, Vatanchian M, Niazmand S, Beheshti F, Rahimi M, Aghaee A, Hadjzadeh MA

Drug Chem Toxicol. 2019 Aug 15:1-8. doi: 10.1080/01480545.2019.1651330. [Epub ahead of print]

Abstract

The present study compared the effects of Portulaca oleracea (P. oleracea) seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress markers and cardiac hypertrophy in a model of thyrotoxicosis. The hyperthyroid state was induced by intraperitoneal injection of levothyroxine (100 µg/kg) for 4 weeks in male adult rats. After 2 weeks, vitamin E (20 mg/kg), valsartan (8 mg/kg), and P. oleracea seed extract (400 mg/kg) were administered in three groups of thyrotoxic rats. The control group was given a daily injection of normal saline. Systolic blood pressure and heart rate were measured on three occasions with tail cuff. At the end of the fourth week, the animals were scarified and serum samples and heart tissue were collected for biochemical and histological studies. The levothyroxine increased heart rate and systolic blood pressure. A lower heart rate and reduced systolic blood pressure were observed in groups receiving valsartan and P. oleracea extract. The heart weight/body weight ratio increased in groups treated with levothyroxine, but in a microscopic study, cardiomyocyte width was not different between the groups. Levothyroxine increased the level of malondyaldehide and NO metabolite but reduced the thiol concentration, superoxide dismutase, and catalase activities. However, treatment with vitamin E and P. oleracea extract increased the thiol concentration, superoxide dismutase and catalase activities while decreasing malondyaldehide level. In addition, treatment with P. oleracea extract and valsartan decreased NO metabolite level. Treatment with P. oleracea extract improved levothyroxine induced oxidative stress and hemodynamic changes. These effects may be for antioxidant components.

Cabral EV, Vieira LD, Sant'Helena BRM, Ribeiro VS, Farias JS, Aires RS, Paz ST, Muzi-Filho H, Paixão AD, Vieyra A

Clin Exp Pharmacol Physiol. 2019 Aug 14. doi: 10.1111/1440-1681.13161. [Epub ahead of print]

Abstract

Maternal salt overload programs cardiovascular and renal alterations in the offspring. However, beneficial and harmful effects of high dose vitamin E supplementation have been described in humans and animals. We investigated the hypothesis as to whether cardiac and renal alterations can be programmed by gestational salt overload, and can become further modified during lactation and after weaning. Male Wistar rats were used, being the offspring of mothers that drank either tap water or 0.3 M NaCl for 20 days before and during pregnancy. α-Tocopherol (0.35 g/kg) was administered to mothers daily during lactation or to their offspring for 3 weeks post-weaning. Systolic blood pressure (tcSBP) was measured in juvenile rats aged 210 days. The response of mean arterial pressure (MAP) and heart rate (HR) to intravenous infusion of angiotensin II (Ang II) was also examined. Left ventricle plasma membrane (PMCA) and sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) activities, and certain parameters of renal function, were measured. Maternal saline programmed for increased body mass and kidney mass/body mass ratio, increased tcSBP, increased mean arterial pressure and heart rate with anomalous response to infused Ang II. In the heart, saline increased PMCA and α-Tocopherol per se increased PMCA/SERCA. In the kidney, the most remarkable result was the silent saline programming of Cr_Cl , which was sensitized for a sharp decrease after α-Tocopherol. In conclusion, the combination of maternal saline overload and high α-Tocopherol immediately after birth leads to simultaneous cardiovascular and renal alterations in the young offspring, like those encountered in type V cardiorenal syndrome.

Nguyen TTH, Eo MY, Seo MH, Myoung H, Kim SM, Lee JH

Eur Arch Otorhinolaryngol. 2019 Aug 14. doi: 10.1007/s00405-019-05600-8. [Epub ahead of print]

Abstract

PURPOSE:

A combination of pentoxifylline (PTX) and tocopherol (TP) is believed to reduce chronic fibrosis and induce bone healing in osteoradionecrosis (ORN) of the mandible, but evidence of its therapeutic effectiveness for cortical bone is lacking. This study was designed to determine the effect of combined PTX and TP (PTX + TP) on mandibular cortical bone remodeling in a rat model of ORN, using micro-CT and histological analysis.

METHODS:

Forty-eight 8-week-old male Sprague-Dawley rats were randomly divided into irradiated (n = 40) and non-irradiated (n = 8) groups. Animals in the irradiated group were divided into four sub-groups, including PTX, TP, PTX + TP, and normal saline. Three weeks after irradiation, mandibular posterior tooth extraction was performed, and animals were sacrificed 7 weeks after irradiation. The mandibles were analyzed using micro-CT and histological evaluation.

RESULTS:

The alveolar bone height, cortical bone thickness, cortical bone volume, and total cortical bone surface of the PTX + TP group were significantly greater than those of other irradiated groups (p < 0.05). In 3D reconstructed images, the residual volumes of cortical and cancellous bone were inadequate in the irradiated groups.

CONCLUSION:

We found that a combination of PTX and TP improved quality and quantity of cortical bone in irradiated rat mandibles, thus providing supporting evidence of its utility as a treatment and prophylactic agent in ORN. We observed inadequate volumes of cortical and cancellous bone in ORN mandibles, suggesting that cortical bone could play an important role in further ORN studies.

Abdul Rahman A, Mokhtar NM, Harun R, Jamal R, Wan Ngah WZ

J Physiol Biochem. 2019 Aug 14. doi: 10.1007/s13105-019-00699-z. [Epub ahead of print]

Abstract

Gamma-tocotrienol (GTT) and hydroxychavicol (HC) exhibit anticancer activity in glioma cancer cells, where the combination of GTT + HC was shown to be more effective than single agent. The aim of this study was to determine the effect of GTT + HC by measuring the cell cycle progression, migration, invasion, and colony formation of glioma cancer cells and elucidating the changes in gene expression mitigated by GTT + HC that are critical to the chemoprevention of glioma cell lines 1321N1 (grade II), SW1783 (grade III), and LN18 (grade IV) using high-throughput RNA sequencing (RNA-seq). Results of gene expression levels and alternative splicing transcripts were validated by qPCR. Exposure of glioma cancer cells to GTT + HC for 24 h promotes cell cycle arrest at G2M and S phases and inhibits cell migration, invasion, and colony formation of glioma cancer cells. The differential gene expression induced by GTT + HC clustered into response to endoplasmic reticulum (ER) stress, cell cycle regulations, apoptosis, cell migration/invasion, cell growth, and DNA repair. Subnetwork analysis of genes altered by GTT + HC revealed central genes, ATF4 and XBP1. The modulation of EIF2AK3, EDN1, and FOXM1 were unique to 1321N1, while CSF1, KLF4, and FGF2 were unique to SW1783. PLK2 and EIF3A gene expressions were only altered in LN18. Moreover, GTT + HC treatment dynamically altered transcripts and alternative splicing expression. GTT + HC showed therapeutic potential against glioma cancer as evident by the inhibition of cell cycle progression, migration, invasion, and colony formation of glioma cancer cells, as well as the changes in gene expression profiles with key targets in ER unfolded protein response pathway, apoptosis, cell cycle, and migration/invasion.

Chin KY, Wong SK, Japar Sidik FZ, Abdul Hamid J, Abas NH, Mohd Ramli ES, Afian Mokhtar S, Rajalingham S, Ima Nirwana S

Int J Environ Res Public Health. 2019 Aug 13;16(16). pii: E2897. doi: 10.3390/ijerph16162897.

Abstract

Osteoarthritis is a degenerative joint disease which primarily affects the articular cartilage and subchondral bones. Since there is an underlying localized inflammatory component in the pathogenesis of osteoarthritis, compounds like tocotrienol with anti-inflammatory properties may be able to retard its progression. This study aimed to determine the effects of oral tocotrienol supplementation on the articular cartilage and subchondral bone in a rat model of osteoarthritis induced by monosodium iodoacetate (MIA). Thirty male Sprague-Dawley rats (three-month-old) were randomized into five groups. Four groups were induced with osteoarthritis (single injection of MIA at week 0) and another served as the sham group. Three of the four groups with osteoarthritis were supplemented with annatto tocotrienol at 50, 100 and 150 mg/kg/day orally for five weeks. At week 5, all rats were sacrificed, and their tibial-femoral joints were harvested for analysis. The results indicated that the groups which received annatto tocotrienol at 100 and 150 mg/kg/day had lower histological scores and cartilage remodeling markers. Annatto tocotrienol at 150 mg/kg/day significantly lowered the osteocalcin levels and osteoclast surface of subchondral bone. In conclusion, annatto tocotrienol may potentially retard the progression of osteoarthritis. Future studies to confirm its mechanism of joint protection should be performed.

Gugliandolo A, Chiricosta L, Silvestro S, Bramanti P, Mazzon E

Brain Sci. 2019 Aug 10;9(8). pii: E196. doi: 10.3390/brainsci9080196.

Abstract

Alzheimer’s disease (AD) is the most common form of dementia worldwide. The hallmarks of AD are the extracellular amyloid plaques, which are formed by amyloid β (Aβ) aggregates derived from the processing of the amyloid precursor protein (APP), and the intraneuronal neurofibrillary tangles, which are formed by the hyperphosphorylated tau protein. The aim of this work was to study the effects of α-tocopherolin retinoic acid differentiated SH-SY5Y neuroblastoma cells exposed to Aβ_1-42 evaluating the transcriptional profile by next-generation sequencing. We observed that α-tocopherol was able to reduce the cytotoxicity induced by Aβ treatment, as demonstrated by Thiazolyl Blue Tetrazolium Bromide (MTT) assay. Moreover, the transcriptomic analysis evidenced that α-tocopherol treatment upregulated genes involved in the non-amyloidogenic processing of APP, while it downregulated the amyloidogenic pathway. Moreover, α-tocopherol modulated the expression of the genes involved in autophagy and the cell cycle, which are both known to be altered in AD. The treatment with α-tocopherolwas also able to reduce oxidative stress, restoring nuclear factor erythroid-derived 2-like 2 (Nrf2) and decreasing inducible nitric oxide synthase (iNOS) levels, as demonstrated by immunocytochemistry.

Wallert M, Ziegler M, Wang X, Maluenda A, Xu X, Yap ML, Witt R, Giles C, Kluge S, Hortmann M, Zhang J, Meikle P, Lorkowski S, Peter K

Redox Biol. 2019 Aug 6;26:101292. doi: 10.1016/j.redox.2019.101292. [Epub ahead of print]

Abstract

OBJECTIVE:

Myocardial infarction (MI) is a leading cause of mortality and morbidity worldwide and new treatment strategies are highly sought-after. Paradoxically, reperfusion of the ischemic myocardium, as achieved with early percutaneous intervention, results in substantial damage to the heart (ischemia/reperfusion injury) caused by cell death due to aggravated inflammatory and oxidative stress responses. Chronic therapy with vitamin E is not effective in reducing the cardiovascular event rate, presumably through failing to reduce atherosclerotic plaque instability. Notably, acute treatment with vitamin E in patients suffering a MI has not been systematically investigated.

METHODS AND RESULTS:

We applied alpha-tocopherol (α-TOH), the strongest anti-oxidant form of vitamin E, in murine cardiac ischemia/reperfusion injury induced by ligation of the left anterior descending coronary artery for 60 min. α-TOH significantly reduced infarct size, restored cardiac function as measured by ejection fraction, fractional shortening, cardiac output, and stroke volume, and prevented pathological changes as assessed by state-of-the-art strain and strain-rate analysis. Cardioprotective mechanisms identified, include a decreased infiltration of neutrophils into cardiac tissue and a systemic anti-inflammatory shift from Ly6C^high to Ly6C^low monocytes. Furthermore, we found a reduction in myeloperoxidase expression and activity, as well as a decrease in reactive oxygen species and the lipid peroxidation markers phosphatidylcholine (PC) (16:0)-9-hydroxyoctadecadienoic acid (HODE) and PC(16:0)-13-HODE) within the infarcted tissue.

CONCLUSION:

Overall, α-TOH inhibits ischemia/reperfusion injury-induced oxidative and inflammatory responses, and ultimately preserves cardiac function. Therefore, our study provides a strong incentive to test vitamin E as an acute therapy in patients suffering a MI.

Wallert M, Ziegler M, Wang X, Maluenda A, Xu X, Yap ML, Witt R, Giles C, Kluge S, Hortmann M, Zhang J, Meikle P, Lorkowski S, Peter K

Redox Biol. 2019 Aug 6;26:101292. doi: 10.1016/j.redox.2019.101292. [Epub ahead of print]

Abstract

OBJECTIVE:

METHODS AND RESULTS:

CONCLUSION:

Erdemli Z, Erdemli ME, Turkoz Y, Gul M, Yigitcan B, Gozukara Bag H

Andrologia. 2019 Aug;51(7):e13292. doi: 10.1111/and.13292. Epub 2019 Apr 17.

Abstract

Thirty rats, with confirmed pregnancies by vaginal smear, were divided into five groups, each including six rats, as the Control, Corn Oil, Vitamin E, Acrylamide, Vitamin E + Acrylamide groups. The births were monitored on the 21st day to select the male rats, and the selected male rats were decapitated at the end of the 8th week. Oxidant-antioxidant parameters, serum hormone levels and histopathological examinations were performed on testis tissues of the rats. It was found that acrylamide (AA) negatively affected the serum hormone levels (Total Testosterone, Progesterone, FSH, LH, Estradiol), oxidant-antioxidant parameters in the tissues (MDA, GSH, NO, SOD, CAT, TAS, TOS) (p < 0.05) and the histological findings (the Johnson’s score, seminiferous tubule diameter, histopathological images), and Vitamin Eadministration resulted with an increase in the total testosterone, progesterone, FSH, LH, GSH, TAS, NO, SOD, CAT levels (p < 0.05) and an improvement in histopathological findings. Currently, it is almost inevitable to be exposed to food-induced AA toxicity and such toxicity is likely to cause lifelong damage. It was concluded that Vitamin E was able to present a protective effect in the testis tissue against AA toxicity; however, further studies are necessary.