RESUMO
Serum and glucocorticoid-regulated kinases (SGK) are serine/threonine kinases that belong to AGC. The SGK-1, which responds to stress, controls a range of ion channels, cell growth, transcription factors, membrane transporters, cellular enzymes, cell survival, proliferation and death. Its expression is highly controlled by various factors such as hyperosmotic or isotonic oxidative stress, cell shrinkage, radiation, high blood sugar, neuronal injury, DNA damage, mechanical stress, thermal shock, excitement, dehydration and ischemia. The structural and functional deterioration that arises after a period of ischemia when blood flow is restored is referred to as ischemia/ reperfusion injury (I/R). The current review discusses the structure, expression, function and degradation of SGK-1 with special emphasis on the various ischemic injuries in different organs such as renal, myocardial, cerebral, intestinal and lungs. Furthermore, this review highlights the various therapeutic agents that activate the SGK-1 pathway and slow down the progression of I/R injuries.
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Proteínas Imediatamente Precoces , Traumatismo por Reperfusão , Humanos , Sobrevivência Celular , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , IsquemiaRESUMO
There is an alarming increase in incidence of fatty liver disease worldwide. The fatty liver disease spectrum disease ranges from simple steatosis (NAFL) to steatohepatitis (NASH) which culminates in cirrhosis and cancer. Altered metabolism is a hallmark feature associated with fatty liver disease and palmitic acid is the most abundant saturated fatty acid, therefore, the aim of this study was to compare metabolic profiles altered in hepatocytes treated with palmitic acid and also the differentially expressed plasma metabolites in spectrum of nonalcoholic fatty liver. The metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) platform. Hepatocyte cell lines PH5CH8 and HepG2 cells when treated with 400 µM dose of palmitic acid showed typical features of steatosis. Metabolomic analysis of lipid treated hepatocyte cell lines showed differential changes in phenylalanine and tyrosine pathways, fatty acid metabolism and bile acids. The key metabolites tryptophan, kynurenine and carnitine differed significantly between subjects with NAFL, NASH and those with cirrhosis. As the tryptophan-kynurenine axis is also involved in denovo synthesis of NAD+, we found significant alterations in the NAD+ related metabolites in both palmitic acid treated and also fatty liver disease with cirrhosis. The study underscores the importance of amino acid and NAD+supplementation as promising strategies in fatty liver disorder.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , NAD/metabolismo , Aminoácidos/metabolismo , Palmitatos/metabolismo , Cinurenina/metabolismo , Triptofano/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/patologia , Ácido Palmítico/farmacologia , Ácido Palmítico/metabolismo , Fígado/metabolismoRESUMO
Coronavirus disease 2019 (COVID-19) causes transmissible viral illness of the respiratory tract prompted by the SARS-CoV-2 virus. COVID-19 is one of the worst global pandemics affecting a large population worldwide and causing catastrophic loss of life. Patients having pre-existing chronic disorders are more susceptible to contracting this viral infection. This pandemic virus is known to cause notable respiratory pathology. Besides, it can also cause extra-pulmonary manifestations. Multiple extra-pulmonary tissues express the SARS-CoV-2 entry receptor, hence causing direct viral tissue damage. This insightful review gives a brief description of the impact of coronavirus on the pulmonary system, extra-pulmonary systems, histopathology, multiorgan consequences, the possible mechanisms associated with the disease, and various potential therapeutic approaches to tackle the manifestations.
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COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMO
Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons, leading to misbalance and loss of coordination. Current therapies are claimed only for symptomatic relief, on long-term use, which causes alteration in basal ganglia, and give rise to various adverse effects like dyskinesia and extra pyramidal side effects, which is reversed and proved to be attenuated with the help of various herbal approaches. Therefore, in order to attenuate the dopaminergic complications, focus of current research has been shifted from dopaminergic to non-dopaminergic strategies. Herbs and herbal remedies seems to be a better option to overcome the complications associated with current dopaminergic therapies. In recent years, various herbs and herbal remedies based on Ayurveda, traditional Chinese and Korean remedies, have become the target of various researches. These herbs and their bioactive compound are being extensively used to treat PD in India, China, Japan, and Korea. The major focus of this current review is to analyze preclinical studies with reference to various herbs, bioactive compounds, and traditional remedies for the management of Parkinson disorder, which will give an insight towards clinical trials.
Assuntos
Doença de Parkinson , Gânglios da Base , Dopamina , Neurônios Dopaminérgicos/patologia , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologiaRESUMO
Almost every human organ has a poor ability to regenerate, notable exceptions are liver, skin, gut, etc. Molecular and cellular underpinnings of liver regeneration might pave the way for novel treatments concerned with chronic liver disorder. Such treatments would eliminate the disadvantages of liver transplantation, such as a scarcity of donor organs, a lengthy waitlist, significant medical expenses, surgical complications, and the necessity for lifelong immunosuppressive medications. Advancement in the development of regenerative therapy is giving hope to those suffering from end-stage liver disorder. The regeneration process is unique, intricate, and well coordinated, which involve the interaction of numerous signaling pathways, cytokines, and growth factor. Various signaling pathways for liver regeneration are HO-1/BER pathway, Tweak/Fn14 signaling pathway, Hippo pathway, Wnt/beta-catenin pathway, Hedgehog signaling pathway, bile acids repairing pathway, serotonin (5HT) pathway, estrogen pathway, thyrotropin-releasing hormone (TRH) pathway, insulin repairing pathway, etc. The in vitro scientific literature revealed that numerous GSK-3 ß inhibitors (LY 2090314, AR-A014418, Tideglusib, Solasodine, CHIR99021, 9-ING-41, SB-216763) play an important role in stimulating the liver regeneration process. Similarly, from the above discussion, the direction is highlighted to emphasize the proposed molecular Wnt/ß-catenin signaling pathway which is associated with GSK-3 ß inhibition for the induction of the repairing and regeneration process.
Assuntos
Doença Hepática Terminal/terapia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Regeneração Hepática/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Inibidores Enzimáticos/farmacologia , Humanos , Regeneração Hepática/fisiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role in the pathogenesis of NAFLD and other metabolic disorders. However, recent scientific upsurge emphasizes on the utility of beneficial gut microbiota and bacteriotherapy in the management of NAFLD. Fecal microbiota transplantation (FMT) is the contemporary therapeutic approach with state-of-the-art methods for the treatment of NAFLD. Other potential therapies include probiotics and prebiotics supplements which are based on alteration of gut microbes to treat NAFLD. In this review, our major focus is on the pathological association of gut microbiota with progression of NAFLD, historical aspects and recent advances in FMT with possible intervention to combat NAFLD and its associated metabolic dysfunctions.
Assuntos
Transplante de Microbiota Fecal , Hepatopatia Gordurosa não Alcoólica/terapia , Animais , Humanos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologiaRESUMO
The liver acts as a manufacturing unit for the production of fetuin-A, which is essential for various physiological characteristics. Scientific research has shown that a moderate upward push in fetuin-A serum levels is associated with a confirmed non-alcoholic fatty liver disease (NAFLD) diagnosis. Fetuin-A modulation is associated with a number of pathophysiological variables that cause liver problems, including insulin receptor signaling deficiencies, adipocyte dysfunction, hepatic inflammation, fibrosis, triacylglycerol production, macrophage invasion, and TLR4 activation. The focus of the present review is on the various molecular pathways, and genetic relevance of mRNA expression of fetuin-A which is correlated with progression of NAFLD. The other major area of exploration in the present review is based on the new targets for the modulation of fetuin-A, like calorie restriction and novel pharmacological agents, such as rosuvastatin, metformin, and pioglitazone which are successfully implicated in the management of various liver-related complications.
Assuntos
Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , alfa-2-Glicoproteína-HS/biossíntese , Adiponectina/antagonistas & inibidores , Adiponectina/biossíntese , Adiponectina/genética , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Restrição Calórica/métodos , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Metformina/farmacologia , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/genética , alfa-2-Glicoproteína-HS/antagonistas & inibidores , alfa-2-Glicoproteína-HS/genéticaRESUMO
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19.
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COVID-19/imunologia , COVID-19/prevenção & controle , Suplementos Nutricionais , Sistema Imunitário/imunologia , Micronutrientes/administração & dosagem , Minerais/administração & dosagem , Vitaminas/administração & dosagem , Humanos , Sistema Imunitário/efeitos dos fármacosRESUMO
The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b.wt. rodent animal model to observe the effect of abnormal fatty acid synthesis. The qRT-PCR was used to evaluate the fatty acid synthase (FASN) expression which is independently allied with diabetes associated fatty liver disorders. To determine the therapeutic potential of three selected drugs, the biochemical parameters and histopathological considerations were utilized. Three subsequent dosage of PTS, ARB and PUR administered (i.e., 30,60 & 120 mg/kg/p.o.) for five weeks significantly alter the serum parameters, oxidative burden in HFD-STZ which, in turn, resulted in diabetic liver injury. It was also revealed that increased mRNA expression of fatty acid synthase (FASN), which is known to promote abnormal fatty acid synthesis through different molecular signaling pathways, was associated with the development of diabetes associated liver injury, this expression was observed to be significantly suppressed by PTS, ARB and PUR treatment. Moreover, the studies of histopathology showed that there was substantial structural improvement after PTS, ARB and PUR treatment. All three selected drugs have been shown to be effective for Diabetic liver injury (DLI) care but PTS shows impressive results compared to other selected drugs.
Assuntos
Complicações do Diabetes/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Hepatopatias/prevenção & controle , Animais , Antraquinonas/uso terapêutico , Antioxidantes/metabolismo , Arbutina/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Dieta Hiperlipídica , Ácido Graxo Sintase Tipo I/biossíntese , Ácido Graxo Sintase Tipo I/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Hepatopatias/etiologia , Masculino , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Estilbenos/uso terapêuticoRESUMO
Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.
Assuntos
Microbioma Gastrointestinal , Hepatite Viral Humana , Microbiota , Transplante de Microbiota Fecal , Hepatite Viral Humana/terapia , Humanos , Cirrose Hepática/terapiaRESUMO
In metabolic disorders like obesity, NAFLD and T2DM, adipocytes are dysfunctional. Hence, pharmacological interventions have importance in preventing differentiation of adipocytes and stimulating lipid uptake. We, therefore, investigated the effects of arbutin (ARB), purpurin (PUR), quercetin (QR), and pterostilbene (PTS) on adipocyte differentiation and lipid uptake using 3T3-L1 adipocytes. Further, in silico docking studies were achieved to investigate interactions of ARB, PUR, QR, and PTS with beta-ketoacyl reductase (KR) and thioesterase (TE) domains of fatty acid synthase (FAS) enzyme. Mature 3T3-L1 adipocytes were used to investigate the anti-adipogenic effect of selected pharmacological agents by Oil Red O staining and in vitro fatty acid uptake analysis. Molecular docking studies were performed to predict the binding interactions of selected compounds with KR and TE domains of FAS enzyme. All these agents significantly decrease the adipocyte differentiation and showed the stimulatory effect on fatty acid uptake in 3T3-L1 adipocytes. However, PTS and PUR proved to be anti-adipogenic, whereas ARB and QR showed significant effect on fatty acid uptake, compared to others. Similarly, all the compounds displayed significant binding interactions with KR and TE domains of FAS enzyme, supporting the results of in vitro studies. Graphical abstract.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Oxirredutases do Álcool/antagonistas & inibidores , Antraquinonas/farmacologia , Arbutina/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintases/antagonistas & inibidores , Simulação de Acoplamento Molecular , Quercetina/farmacologia , Estilbenos/farmacologia , Células 3T3-L1 , Adipócitos/enzimologia , Oxirredutases do Álcool/metabolismo , Animais , Antraquinonas/química , Antraquinonas/farmacocinética , Arbutina/química , Arbutina/farmacocinética , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Camundongos , Estrutura Molecular , Quercetina/química , Quercetina/farmacocinética , Estilbenos/química , Estilbenos/farmacocinética , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Poor dietary habits such as an over consumption of high fructose and high fat diet are considered as the major culprit for the induction of diabetes associated liver injury. Diabetes mellitus is a metabolic disorder that affects various vital organs of the body especially the kidney, brain, heart, and liver. The high fructose and high fat (HFHF) diet worsen the metabolic conditions by producing various pathogenic burdens such as oxidative stress, inflammation, etc. on liver. The hyperlipidemic and hyperglycemic conditions induced by HFHF diet leads to the generation of various proinflammatory mediators like TNFα, interleukin and cytokines. AIM AND METHODS: The systematic bibliographical literature survey was done with the help of PubMed, Google scholar and MedLine to identify all pathological and molecular concerened with HFHF induced diabetic liver injury. The consumption of HFHF diet leads to an increase in mitochondrial oxidative stress thereby decreases the liver protective antioxidants required for cell viability. HFHF diet disturbs lipid and lipoprotein clearance by elevating the level of apolipoprotein CIII and impairing the hydrolysis of triglyceride. As a result, there is an increase in free fatty acid concentration, triglycerides and diacylglycerol in the liver which further triggers the situation of insulin resistance. CONCLUSION: The focus of present review is based upon the various pathological, genetic and molecular mechanism involved in the development of high-fat high fructose diet induced diabetic liver injury. However, the current review also documented few shreds of evidence related to various microRNAs (miR-31, miR-33a, miR-34a, miR-144, miR-146b, miR-150) concerned to HFHF diet which play an important role in the pathogenesis of diabetes associated liver injury Dietary life style modification may prove beneficial in the management of various metabolic disorders.
Assuntos
Complicações do Diabetes/etiologia , Dieta Hiperlipídica , Frutose/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/etiologia , Microbioma Gastrointestinal , Humanos , Resistência à Insulina , Lipídeos/sangue , MicroRNAs , Estresse OxidativoRESUMO
The anticancer, anti-inflammatory and antioxidant properties of Purpurin were generated from in vitro studies, and no scientific reports were found on its safety and efficacy, related to their in vivo studies; thus, the present study was focused on acute oral toxicity of purpurin in female Wistar rats as per the OECD 423 guidelines. In this study, purpurin was administered at starting dosage of 300 mg/kg followed by 2000 mg/kg, p.o, and animals were observed for toxic signs at 24 h and for the next 14 days to different animal groups. Animals were observed for mortality, behavioral changes, biochemistry, hematological parameters, and histopathological examination after a follow up on the 14th day. The oral lethal dose for mice was greater than 2000 mg/kg, b.wt. in female rats and classified under category 5 as per the acute oral toxicity study. It was found that there were no significant differences in body weight changes, food/water intake, hematology, and clinical biochemistry. The histopathological study directly depicted that there were no pathological changes observed in the vital organs of rats treated with the different dose of Purpurin. The present work advocates that an acute oral administration of Purpurin was found to be a non-toxic and safe drug in the tested experimental conditions.
Assuntos
Antraquinonas/toxicidade , Administração Oral , Animais , Anti-Inflamatórios/toxicidade , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/toxicidade , Feminino , Guias como Assunto , Dose Letal Mediana , Organização para a Cooperação e Desenvolvimento Econômico , Ratos Wistar , Testes de Toxicidade AgudaRESUMO
Diabetes mellitus is a rising epidemic in most part of the world and is often associated with multiple organ disorders such as kidney, liver, and cardiovascular diseases. Liver is a major metabolic hub, and the metabolic disorders associated with diabetes result in liver dysfunctions culminating in spectrum of liver diseases such as fatty liver disorders, cirrhosis, and hepatocellular carcinoma. The intervention strategies to prevent diabetes-associated liver injury require an overall understanding of the key factors and molecular pathways which can be strategically targeted. The present review focuses on some of the key aspects of fatty acid metabolism, fetuin-A regulation, inflammatory pathways, and genetic factors associated with insulin resistance, dyslipidemia, hyperglycemia, oxidative stress, and so on involved in the nexus between diabetes and liver injury. Further recent interventions, pharmacological target, and newer therapeutic agents are discussed briefly for the better clinical management of diabetes-associated hepatic disorders.
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The inappropriate dietary habits lead to the onset of age-related pathologies which include diabetes and cardiovascular ailments. Dietary restriction and nutritional therapy play an important role in the prevention of these chronic ailments. Preclinical research provides a basis for the therapeutic exploration of new dietary interventions for the clinical trials to potentiate the scientific management of diabetes and its related complications which further help in translating these nutritional improvements from bench to bedside. Within the same context, numerous therapeutically proved preclinical dietary interventions like high-fiber diet, caloric restriction, soy isoflavone-containing diets, etc., have shown the promising results for the management of diabetes and the associated complications. The focus of the present review is to highlight the various preclinical evidences of diet restriction for the management of diabetes and which will be helpful for enlightening the new ideas of nutritional therapy for future research exploration. In addition, some potential approaches are also discussed which are associated with various nutritional interventions to combat progressive diabetes and the associated disorders. Graphical abstract á .
Assuntos
Restrição Calórica , Diabetes Mellitus/dietoterapia , Animais , Dieta , HumanosRESUMO
BACKGROUND: Carbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders. The present study tested the influence of carbohydrate-energy restricted diet (CR) on type-1 diabetes induced renal dysfunction, hypoxia and structural alterations against diabetic rat group fed control diet (ad libitium). METHODS: Male wistar rats weighing between 180 and 190 g were subjected to 30% carbohydrate energy restricted diet (CR) and diabetes was induced by administration of streptozotocin (45 mg/kg., i.p). Assessment of renal function was done after 4 weeks by determining the serum levels of creatinine, BUN, proteinuria. Oxidative stress was determined by estimating the reduced glutathione, malonaldehyde levels, catalase activity and extent of renal hypoxia by estimating the HIF-1α levels in kidney tissue homogenates. Histological studies were conducted on kidney sections using hematoxylin and eosin, periodic acid-schiff staining. RESULTS: Diabetic rats exhibited marked hyperglycemia and renal dysfunction developed in diabetic rats fed control diet (ad libitium) as shown by significantly elevated levels of serum creatinine, BUN and massive proteinuria after 4 weeks period. CR diet treatment in diabetic rats significantly lowered hyperglycemia, reversed the above renal functional abnormalities, reduced oxidative stress and enhanced HIF-1α levels. Furthermore histological examination of kidney sections from CR diet treated diabetic rat group showed absence of glomerular hypertrophy, mesangial expansion and tubular vacoulations. CONCLUSION: Our results demonstrated that CR diet treatment in diabetic rats attenuated renal damage by reducing oxidative stress and preventing the development of hypoxia by up-regulating HIF-1α levels.
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The HMG Co-enzyme inhibitors and new lipid-modifying agents expand their new therapeutic target options in the field of medical profession. Statins have been described as the most effective class of drugs to reduce serum cholesterol levels. Since the discovery of the first statin nearly 30 years ago, these drugs have become the main therapeutic approach to lower cholesterol levels. The present scientific research demonstrates numerous non-lipid modifiable effects of statins termed as pleiotropic effects of statins, which could be beneficial for the treatment of various devastating disorders. The most important positive effects of statins are anti-inflammatory, anti-proliferative, antioxidant, immunomodulatory, neuroprotective, anti-diabetes, and antithrombotic, improving endothelial dysfunction and attenuating vascular remodeling besides many others which are discussed under the scope of this review. In particular, inhibition of Rho and its downstream target, Rho-associated coiled-coil-containing protein kinase (ROCK), and their agonistic action on peroxisome proliferator-activated receptors (PPARs) can be viewed as the principle mechanisms underlying the pleiotropic effects of statins. With gradually increasing knowledge of new therapeutic targets of statins, their use has also been advocated in chronic inflammatory disorders for example rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE). In the scope of review, we highlight statins and their pleiotropic effects with reference to their harmful and beneficial effects as a novel approach for their use in the treatment of devastating disorders. Graphical abstract Pleiotropic effect of statins.
Assuntos
Desenho de Fármacos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Dislipidemias/sangue , Dislipidemias/diagnóstico , História do Século XX , História do Século XXI , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/história , Fatores Imunológicos/uso terapêutico , Lipídeos/sangue , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Agonistas do Receptor Purinérgico P1/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/metabolismoRESUMO
BACKGROUND: Neuropathic pain is associated with severe chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli (hyperalgesia) and pain perceived in response to non-noxious stimuli (allodynia). Morphine is effective treatment for neuropathic pain but produces tolerance on chronic use. The present study was designed to explore the anti-nociceptive and anti-hyperalgesic effect of grape seed extract using sciatic nerve ligation-induced neuropathic pain in rats. METHODS: Chronic constructive injury (CCI) was performed under anesthesia, on one side leg exposed by making a skin incision, and chromic gut ligatures were tied loosely around the sciatic nerve at 1 mm intervals. The treatment with grape seed proanthocyanidin extract (GSPE) (100 and 200 mg/kg, p.o.) was initiated on 7th day post-surgery and continued for next 14 days. Morphine (10 mg/kg, s.c.) alone and morphine in combination with GSPE (100 mg/kg, p.o.) were administered in CCI rats for 5 days starting from 7th day. On 3rd, 7th, 14th and 21st day, behavioral parameters (mechanical allodynia and thermal hyperalgesia) were assessed. Then the animals were killed on 22nd day and biochemical parameters [reduced glutathione (GSH), lipid peroxidation (LPO), catalase, nitrite, superoxide dismutase (SOD)] were assessed. RESULTS: Ligation of the sciatic nerve significantly induced mechanical allodynia and thermal hyperalgesia and induces oxidative stress (increase in LPO and nitrite) and decline of anti-oxidant enzyme levels (catalase, SOD, GSH) in sciatic nerve homogenate. GSPE (100 and 200 mg/kg, p.o.) attenuated all the behavioural and biochemical parameters. Morphine also significantly reversed the symptoms of neuropathic pain but produced tolerance after 5 days. Further, co-treatment of GSPE (100 mg/kg) with morphine (10 mg/kg, s.c.) in CCI rats significantly reversed the morphine tolerance and enhanced its anti-hyperalgesic effect as compared to the morphine-alone-treated group. CONCLUSIONS: In the present set of experiments, GSPE showed a significant anti-hyperalgesic and anti-nociceptive effect in rats.
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Analgésicos/farmacologia , Extrato de Sementes de Uva/farmacologia , Hiperalgesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Proantocianidinas/farmacologia , Analgésicos/administração & dosagem , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Extrato de Sementes de Uva/administração & dosagem , Masculino , Morfina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/administração & dosagem , Ratos , Ratos WistarRESUMO
INTRODUCTION: Liver is the largest and important organ in the body, involved in the metabolism of food and drugs. Liver diseases are potentially life threatening for humans. The etiology of liver disorder varied due to different reasons like autoimmune disorder, viral infection, toxic chemical, and due to changing diet style. Liver injury produces pathological changes like increase level of SGOT, SGPT, TB and generation of free radical radicals. METHODS: A better understanding of primary mechanisms is mandatory for designing of new therapeutic drugs. Therefore, animal models are being developed to mimic human liver diseases. Animal models are being used for several decades to study the pathogenesis of liver disorders and related toxicities. CONCLUSION: In this review, we revealed various animal models with their merits and demerits. Our main focus is to explore all new and traditional animal models under broad classification like non-invasive, invasive and genetic models which directly or indirectly produce hepatotoxicity.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatopatias/patologia , Fígado/metabolismo , Fígado/patologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Humanos , Hepatopatias/genética , Hepatopatias/metabolismoRESUMO
Traditional herbal drugs are wonderful remedies for the treatment of various devastating disorders. Recently, there has been a change in a universal fashion from synthetic to herbal medicine, which is like homecoming to nature. In the present situation, the dietary changes lead to liver disorders like non-alcoholic and alcoholic fatty liver disorders. India is one of the world's twelve leading biodiversity centers with the presence of over 45,000 diverse plant species, out of this about 15,000-20,000 plants have good medicinal and therapeutic properties of which only about 7,000-7,500 are being used by traditional practitioners. Hepatic injury accounts for 3.5%-9.5% of all adverse drug reaction reports and up to 14.7% of fatal adverse reaction. Hepatic disorders/toxicity can occur by several mechanisms like Cytochrome P450 activation, lipid peroxidation, Induction of nitric acid synthase, mitochondrial dysfunction, activation of pro-inflammatory mediators and Bile acid-induced liver cell death. There are a number of drugs or therapies available for the treatment of hepatic disorders, but still there is a need for the novel drug discovery which can target multiple disease pathways. Traditional medicines have exhaustive ancient and scientific literature for curing a lot of life threatening disorders with less or no side effects. There are number of scientifically proved hepatoprotective herbal drugs like Andrographis paniculata, Ocimum sanctum, Solanum nigrum, Silybum marianum, Phyllanthus niruri etc. which are widely used for the treatment of liver disorders. However, there are various herbal plants and phytoconstituents, which are found to be hepatotoxic like Lanata camra Linn, Symphytum officinale, Azadirachta indica, Amantia phalloides etc. This review emphasizes on both sides of the coin like crucial aspects of phytoconstituents with reference to their hepatoprotective as well as hepatotoxic effects linked to use of herbal preparations.