Protective effects of melatonin on mitochondrial injury and neonatal neuron apoptosis induced by maternal hypothyroidism

2019 ◽  
Vol 2 (4) ◽  
pp. 42-60
Author(s):  
Mariyah Hidayat ◽  
Saba Khaliq ◽  
Abdullah Khurram ◽  
Khalid P Pervaiz Lone
Keyword(s):  
Thyroid Gland ◽  
Neuronal Apoptosis ◽  
Mitochondrial Outer Membrane ◽  
Protective Effects ◽  
Gene Expressions ◽  
Protective Mechanisms ◽  
Apoptotic Pathway ◽  
Beneficial Effects ◽  
Melatonin Administration ◽  
Neonatal Brain Damage

In the current study, we reported the beneficial effects of melatonin in preventing neonatal neuronal apoptosis induced by maternal hypothyroidism. During the gestation and early lactation stages, the mother rats were given propylthiouracil (PTU) to inhibit their thyroid gland activity which resulted in the increased serum TSH and reduced T4 levels. This maternal hypothyroidism caused neuronal apoptosis of their pups, particularly in the CA3 area of hippocampus. Melatonin administration preserved function of thyroid gland and significantly reduced the apoptosis. Further studies have uncovered the potentially protective mechanisms of melatonin, that is, as a mitochondrial targeted antioxidant, melatonin preserves the mitochondrial outer membrane, inhibits the release of cytochrome C from mitochondria to cytoplasm and down regulates the gene expressions of Bax, along with caspases 3 and 9. Thus, melatonin breaks the mitochondria related apoptotic pathway to suppress the neuronal apoptosis induced by the maternal hypothyroidism.  Considering the limited remedies to effectively treat hypothyroidism associated neonatal brain damage, melatonin may provide an alternative method for this disorder.

Protective Effect of Thyroxine on Minocycline Induced Thyroid Gland Damage

2020 ◽  
Author(s):  
Tahira Assad
Keyword(s):  
Thyroid Gland ◽  
Concomitant Administration ◽  
Treated Group ◽  
Control Group ◽  
Similar Amount ◽  
Protective Effects ◽  
Absolute Weight ◽  
Beneficial Effects ◽  
Group A ◽  
Group B

Background: Thyroxine has shown beneficial effects on intelligence, learning, and memory process in patients of congenital hypothyroidism. Minocycline has been used in clinical practice for various indications and reported to have anti-thyroid effects. This study was specifically designed to observe the role of thyroxine on minocycline induced damage to thyroid gland. Methods: This experimental study was undertaken at Anatomy department of BMSI, JPMC, Karachi, for eight weeks, from October to November 2019. Thirty adult (10-12 months) male guinea pigs, weighing from 450-650 gm were obtained and divided into 3 groups. Group A served as control, group B was given Minocycline 0.02mg/gram/day once daily and group C was administered Minocycline in similar amount as group B along with thyroxine 0.5µg/gram/day for the same duration. Dosing was continued for 8 weeks, at the completion of which all the animals were sacrificed. Thyroid gland was processed and tissue sections were stained with Haematoxylin and Eosin for morphology. Results: The absolute weight of thyroid gland was significantly increased (p<0.001) in minocycline treated group B animals compared to the control animals, whereas substantial decrease (p<0.01) in absolute weight of thyroid gland was witnessed in group C in comparison to group B animals. The follicular cells showed hypertrophy and shrinkage of colloid in the thyroid follicles. These changes were prevented when animals were co-administered with thyroxine and minocycline in Group C. Conclusion: Concomitant administration of thyroxine with the antimicrobial drug minocycline showed protective effects of thyroxine on Minocycline induced damage to thyroid gland of animals.

Therapeutic Effects of Blue Honeysuckle on Lesions of Hyperthyroidism in Rats

2016 ◽  
Vol 44 (07) ◽  
pp. 1441-1456 ◽  
Author(s):  
Sang-In Park ◽  
Young Joon Lee ◽  
Seong Hun Choi ◽  
Soo Jin Park ◽  
Chang-Hyun Song ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Body Weight Loss ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Epididymal Fat ◽  
Endogenous Antioxidant ◽  
Fat Pads ◽  
Blue Honeysuckle

Hyperthyroidism is a hypermetabolic syndrome characterized by an overproduction of thyroid hormones, which enhances the hormone-induced oxidative stress responsible for some complications in the liver, heart and muscle. Blue honeysuckle (BH) is an edible berry, rich in polyphenols, especially flavonoids or anthocyanins, known as strong antioxidants. The chemo-protective activities of the berry have been connected to the improvement of symptoms in cancer, diabetes mellitus, tumor or cardiovascular diseases. Therefore, the therapeutic effects of BH were examined in hyperthyroidism rat model. The hyperthyroidism was induced by injection with levothyroxine (LT4), and the model was treated with distilled water (LT4 control), propylthiouracil (PTU) or BH at 3 dosages of 500, 250 and 125[Formula: see text]mg/kg. The treatment was performed once a day for 15 days. Compared to LT4 control, the oral administration of BH dose-dependently ameliorated the hyperthyroidism, reducing thyroid hormones and increasing thyroid stimulating hormones. These effects were accompanied by improvement of body weight loss and atrophy in the thyroid gland, liver and epididymal fat pads. BH treatments also reduced the levels of hepatic enzymes (AST and ALT), which suggests BH exerts protective effects on hepatocytes. BH might also be involved in the augmentation of the anti-oxidant activities, supported by increased endogenous antioxidant (glutathione). In addition, the histopathological analyses revealed the beneficial effects of BH on the atrophic changes and cellular injuries in the thyroid gland, liver and epididymal fat pads. The therapeutic potentials of BH were either similar or more effective than PTU. These results provide valuable information that will guide more detailed studies to use the BH as a complementary and alternative medicine.

Changes in morphology and gene expressions of neonatally X-irradiated thyroid gland in rats

2020 ◽  
Author(s):  
Nariaki Fujimoto ◽  
Mutsumi Matsuu-Matsuyama ◽  
Masahiro Nakashima
Keyword(s):  
Thyroid Gland ◽  
Gene Expressions

Role of Heart Rate Reduction in the Management of Myocarditis

2018 ◽  
Vol 24 (3) ◽  
pp. 365-378 ◽  
Author(s):  
Chen Guang-Yi ◽  
Ge Li-Sha ◽  
Li Yue-Chun
Keyword(s):  
Heart Rate ◽  
Nitrosative Stress ◽  
Ventricular Remodeling ◽  
Animal Experiments ◽  
Viral Myocarditis ◽  
Protective Effects ◽  
Heart Rate Reduction ◽  
Rate Reduction ◽  
Beneficial Effects ◽  
Biological Technique

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

scholarly journals Melatonin Successfully Rescues the Hippocampal Molecular Machinery and Enhances Anti-oxidative Activity Following Early-Life Sleep Deprivation Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 774
Author(s):  
Hung-Ming Chang ◽  
Hsing-Chun Lin ◽  
Hsin-Lin Cheng ◽  
Chih-Kai Liao ◽  
To-Jung Tseng ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Early Life ◽  
Cognitive Activity ◽  
Oxidative Activity ◽  
Protective Effects ◽  
Long Term Effects ◽  
Ionic Distribution ◽  
Melatonin Administration ◽  
Molecular Machinery ◽  
Underlying Mechanisms

Early-life sleep deprivation (ESD) is a serious condition with severe cognitive sequelae. Considering hippocampus plays an essential role in cognitive regulation, the present study aims to determine whether melatonin, a neuroendocrine beard with significant anti-oxidative activity, would greatly depress the hippocampal oxidative stress, improves the molecular machinery, and consequently exerts the neuro-protective effects following ESD. Male weanling Wistar rats (postnatal day 21) were subjected to ESD for three weeks. During this period, the animals were administered normal saline or melatonin (10 mg/kg) via intraperitoneal injection between 09:00 and 09:30 daily. After three cycles of ESD, the animals were kept under normal sleep/wake cycle until they reached adulthood and were sacrificed. The results indicated that ESD causes long-term effects, such as impairment of ionic distribution, interruption of the expressions of neurotransmitters and receptors, decreases in the levels of several antioxidant enzymes, and impairment of several signaling pathways, which contribute to neuronal death in hippocampal regions. Melatonin administration during ESD prevented these effects. Quantitative evaluation of cells also revealed a higher number of neurons in the melatonin-treated animals when compared with the saline-treated animals. As the hippocampus is critical to cognitive activity, preserving or even improving the hippocampal molecular machinery by melatonin during ESD not only helps us to better understand the underlying mechanisms of ESD-induced neuronal dysfunction, but also the therapeutic use of melatonin to counteract ESD-induced neuronal deficiency.

scholarly journals Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  
Keyword(s):  
Biological Activity ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
In Vitro Digestion ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Digestion Process ◽  
Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease

2012 ◽  
Vol 302 (3) ◽  
pp. R321-R330 ◽  
Author(s):  
Ahmed A. Elmarakby
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Animal Models ◽  
Vascular Function ◽  
Organ Damage ◽  
Reduce Blood Pressure ◽  
Experimental Models ◽  
Epoxyeicosatrienoic Acids ◽  
Protective Effects ◽  
Protective Mechanisms

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome.

scholarly journals Antioxidant Strategies and Respiratory Disease of the Preterm Newborn: An Update

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chiara Poggi ◽  
Carlo Dani
Keyword(s):  
Lung Damage ◽  
Preterm Newborn ◽  
Beneficial Effects ◽  
Melatonin Administration ◽  
Targeted Treatments ◽  
Wide Range ◽  
Nonenzymatic Antioxidants ◽  
Respiratory Outcomes ◽  
Preterm Newborns

Preterm newborns are challenged by an excessive oxidative burden, as a result of several perinatal stimuli, as intrauterine infections, resuscitation, mechanical ventilation, and postnatal complications, in the presence of immature antioxidant capacities. “Oxygen radical disease of neonatology” comprises a wide range of conditions sharing a common pathway of pathogenesis and includes bronchopulmonary dysplasia (BPD) and other main complications of prematurity. Antioxidant strategies may be beneficial in the prevention and treatment of oxidative stress- (OS-) related lung disease of the preterm newborn. Endotracheal supplementation or lung-targeted overexpression of superoxide dismutase was proved to reduce lung damage in several models; however, the supplementation in preterm newborn failed to reduce the risk of BPD, although long-term respiratory outcomes were improved. Also melatonin administration to small cohorts of preterm newborns suggested beneficial effects on lung OS. The possibility to identify single nucleotide polymorphism affecting the risk of BPD may help to identify specific populations with particularly high risk of OS-related diseases and may pose the basis for individually targeted treatments. Finally, surfactant replacement may lead to local anti-inflammatory and antioxidant effects, thanks to specific enzymatic and nonenzymatic antioxidants naturally present in animal surfactants.

Abstract 119: Protective Effects of Chloroquine on Ischemic and Nutrient Depleted Muscle are Mediated by HMGB1 and Caspase-1

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Ulka Sachdev ◽  
Xiangdong Cui ◽  
Qian Sun ◽  
Edith Tzeng ◽  
Alex Chen ◽  
...  
Keyword(s):  
Culture Media ◽  
Statistical Significance ◽  
High Mobility ◽  
Maximal Activity ◽  
Arterial Disease ◽  
Protective Effects ◽  
Artery Ligation ◽  
Beneficial Effects ◽  
Caspase 1 ◽  
Ldh Activity

Introduction: Millions of Americans are at risk for amputation from severe peripheral arterial disease (PAD) when surgery is not possible. Pro-regenerative and angiogenic agents may improve outcome in that setting. Chloroquine (CQ) promotes wound healing in scleroderma but has not been tested in PAD. CQ promotes healing of ischemic muscle, increases muscle high mobility group box 1 (HMGB1), an inflammatory, pro-angiogenic protein, and activates caspase-1 in myoblasts. We hypothesize that HMGB1 mediates protective effects of CQ and is regulated by caspase-1 in muscle. Controlled rather than indiscriminate release of HMGB1 from damaged muscle may be protective during ischemia. Methods: C2C12 myoblasts in low serum were treated with CQ (0-50μM) ± Ac-YVAD-cmk (10 μg/ml), a caspase-1 inhibitor. HMGB1 release in supernatants was measured using ELISA. Cytotoxicity was assessed by comparing spontaneous lactate dehydrogenase (LDH) activity in culture media from control, treated and maximally lysed cells. CQ (50μg/ml) or placebo treated wild-type and inducible HMGB1 knockout (iHMGB1KO) mice underwent unilateral femoral artery ligation (FAL). Laser Doppler perfusion imaging (LDPI) before and 1,7,14 and 21d after FAL was reported as % improvement over time. ANOVA was used to assess statistical significance among groups. Results: CQ (5-10uM) attenuated spontaneous LDH leak after 12h from serum-depleted myoblasts (p <0.01, N=3), and modestly increased HMGB1 release (p <0.001, N=3). Ac-YVAD-cmk reversed the cytoprotective effects of CQ, significantly raising both LDH activity to 55% of maximal activity and HMGB1 in the supernatant. Compared to d1 post FAL, CQ improved perfusion recovery in WT mice by 300-800% over 21 days (p<0.03, N=7/group), but not in iHMGB1KO mice. Conclusion: We present the novel finding that in nutrient-depleted myoblasts, caspase-1 mediates the survival benefits of CQ and regulates HMGB1 release. In turn, HMGB1 is critical for CQ’s beneficial effects on perfusion after FAL, another stress condition. Regulated HMGB1 release may be immunomodulatory, regenerative and modifiable with drugs like CQ. Altering survival and inflammatory pathways through CQ may present a novel therapeutic strategy in PAD.

Resveratrol and cardiac fibrosis prevention and treatment

2021 ◽  
Vol 22 ◽  
Author(s):  
Parinaz Zivarpour ◽  
Željko Reiner ◽  
Jamal Hallajzadeh ◽  
Liaosadat Mirsafaei
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiac Fibrosis ◽  
Therapeutic Potential ◽  
Developed Countries ◽  
Clinical Results ◽  
Matrix Proteins ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Laboratory Models

: Cardiovascular diseases are some of the major causes of morbidity and mortality in developed or developing countries but in developed countries as well. Cardiac fibrosis is one of the most often pathological changes of heart tissues. It occurs as a result of extracellular matrix proteins accumulation at myocardia. Cardiac fibrosis results in impaired cardiac systolic and diastolic functions and is associated with other effects. Therapies with medicines have not been sufficiently successful in treating chronic diseases such as CVD. Therefore, the interest for therapeutic potential of natural compounds and medicinal plants has increased. Plants such as grapes, berries and peanuts contain a polyphenolic compound called "resveratrol" which has been reported to have various therapeutic properties for a variety of diseases. Studies on laboratory models that show that resveratrol has beneficial effects on cardiovascular diseases including myocardial infarction, high blood pressure cardiomyopathy, thrombosis, cardiac fibrosis, and atherosclerosis. In vitro animal models using resveratrol indicated protective effects on the heart by neutralizing reactive oxygen species, preventing inflammation, increasing neoangiogenesis, dilating blood vessels, suppressing apoptosis and delaying atherosclerosis. In this review, we are presenting experimental and clinical results of studies concerning resveratrol effects on cardiac fibrosis as a CVD outcome in humans.

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