Protective and therapeutic effects of Chamomilla Recutita extract on subacute ethanol intoxication in white albino rats

Medicinal plants may provide an effective remedy for the enormous health burden posed by alcohol abuse. The aim of this study was to investigate putative protective and therapeutic effects of an aqueous extract of Chamomilla recutita (CHR) on alcohol-induced hepato-nephrotoxicity and pancytopenia in rats. Rats fed only alcohol developed hepato-nephrotoxicity as indicated by significant increases in the levels of all hepatic enzyme markers [alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GTT)], significantly decreased levels of total protein and increased levels of serum creatinine and urea. Ethanol administered rats also developed pancytopeniawithdecreased levels of total red blood cells (RBC's), white blood cells (WBC's) and platelets and macrocytic, hypochromic anemia. Oral administration of CHR extract for 28 days to normal rats confirmed its safe use with all the above biochemical and hematological parameters remaining within their normal levels. Pre-treatment or post-treatment with CHR to ethanol administered rats ameliorated the deleterious effects of ethanol on all biochemical and hematological parameters. CHR effect was more potent in pretreated- than in post-treated group. The results also show that a diminution of oxidative stress is one mechanism by which CHR extract exerts potent protective and mild therapeutic effects against alcohol-induced hepato-nephrotoxicity and pancytopenia.Keywords: Chamomilla, alcohol, liver, kidney, hematology, protection, therapyAfrican Journal of Biotechnology Vol. 12(18), pp. 2378-238

Protective Role of Ficus carica Stem Extract against Hepatic Oxidative Damage Induced by Methanol in Male Wistar Rats

The present study was aimed to investigate the antioxidant activity of Ficus carica stem extract (FE) in methanol-induced hepatotoxicity in male Wistar rats. The rats were divided into two batches: 16 control rats (C) drinking tap water and 16 treated rats drinking Ficus carica stem extract for six weeks. Then, each group was divided into two subgroups, and one of them was intraperitoneally injected (i.p.) daily methanol at a dose of 2.37 g/kg body weight i.p. for 30 days, for four weeks. The results showed that FE was found to contain large amounts of polyphenols and carotenoids. The treatment with methanol exhibited a significant increase of serum hepatic biochemical parameters (ALT, AST, ALP, and LDH) and hepatic lipid peroxidation. Hepatic antioxidant enzymes, namely, SOD, CAT, and GSH-Px, were significantly decreased in methanol-treated animals. FE treatment prior to methanol intoxication has significant role in protecting animals from methanol-induced hepatic oxidative damage

The in Vivo Deleterious Effects of Ethanol

Oxidative stress, which is defined as an imbalance between pro-oxidants and antioxidants, has been demonstrated to mediate the pathogenesis of ethanol-induced injury. Senescence-accelerated mice prone P8 (SAMP8) is considered an excellent model for rode

ETHANOL-INDUCED ALTERATIONS IN CARDIAC ENZYMES–AMELIORATIVE EFFECT OF THESPESIA POPULNEA LEAF EXTRACT

Objective: This study covers the estimation of changes in cardiac enzymes such as ATPases and antioxidant enzymes following ethanol-administration in rats, and the possible ameliorative effect of leaf extract of the plant Thespesia populnea (TP) on these changes.Methods: Male adult Wistar rats were divided into 10 groups of six rats each. Vehicle controls received 5% gum acacia. Experimental groups received ethanol (20%, 2g/kg); or TP leaf extract (200 mg/kg and 400 mg/kg respectively); or vitamin E (25 mg/kg); or carvedilol (1 mg/kg) per orally every morning for 6 w, individually as well as in combination with ethanol. Following this, changes in the activities of Na+ ATPase, Ca2+ATPase, Mg2+ATPase, and antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were determined in the heart tissue and compared with those in vehicle control.Results: Ethanol (20%, 2g/kg) treatment caused a reduction from the vehicle control in activities of all the examined enzymes, with minimal reduction in Mg2+ ATPase activity (29.26%) and maximal reduction in CAT activity (71.05%). With TP leaf extracts of 200 and 400 mg/kg, vitamin E and carvedilol individually, the vehicle controls showed percent changes in enzyme activities ranging from ‒8.24% for Mg2+ ATPase activity to+109.39% for Na+ ATPase activity caused by carvedilol. When administered along with ethanol, TP leaf extracts, vitamin E and carvedilol reversed the effect of ethanol to various degrees and brought back the enzyme activities to near vehicle control levels. While recovery with 200 mg Thespesia leaf extract was less, ranging from 24.1% for Mg2+ATPase activity to 190.91% for CAT activity, 400 mg Thespesia extract effected a greater recovery, with a minimum of 48.19% for Mg2+ ATPase activity and a maximum of 222.73% for CAT activity, as compared with ethanol-treated rats as controls. These effects could be interpreted in terms of the adverse effects of ethanol on cardiac function and the ameliorative effects, primarily the antioxidant potential, of TP leaf extracts, vitamin E and carvedilol.Conclusion: The restoration of enzyme activities with TP leaf extract may promote recovery of cardiac tissue from oxidative damage. Results from the current study indicate that treatment with TP leaf extract reduces ethanol-induced oxidative stress in rat heart and hence may help prevent cardiac damage.Â

The Turkish Clinical Microbiology and Infectious Diseases Society (KLİMİK) Evidence-Based Guideline for the Diagnosis and Treatment of Brucellosis, 2023

Bruselloz, dünyada ve ülkemizde çok yaygın olarak görülmesine rağmen hastalığın tanı ve tedavisini yönlendirmede kullanılabilecek kanıta dayalı bir rehber bulunmamaktadır. Bu rehber, brusellozun tanı ve tedavisi ile ilgilenen farklı uzmanlık alanlarından hekimlere kanıta dayalı öneriler sunmak üzere Türk Klinik Mikrobiyoloji ve İnfeksiyon Has- talıkları Derneği tarafından hazırlanmıştır. Rehberin hazırlanmasında, ABD İnfeksiyon Hastalıkları Derneği (IDSA)’nin Klinik Uygulama Rehberi Geliştirme Kı- lavuzu önerileri esas alınmıştır. Rehberi hazırlayan grup üyeleri tarafından, bruselloz tanı ve tedavisinde önemli olduğu düşünülen 20 soru belirlenmiş ve PICO [hasta/popülasyon (P), müdahale/indikator (I), karşılaştırma/kontrol (C), sonuç (O)] formatında oluşturulan bu sorulara yanıt verebilecek yayınlar, ULAKBİM TR Dizin, PubMed ve Cochrane veritabanlarından, tarih kısıtlaması olmadan taranmıştır. Her bir PICO sorusu ve her bir ayrı sonlanım için kanıtların derecelendirilmesinde ve önerilerin gücünün belirlenmesinde “Grading of Recommendations, Assessment, Develop- ment and Evaluation (GRADE) Working Group” yöntemi kullanılmıştır. PICO sorularına yanıt oluşturabilecek şekilde karşılaştırmalı klinik araştırmaların olması halinde bunların meta-analizleri, olmaması halindeyse olgu sunumları ve olgu serilerinden elde edilen verilerle “individual participant data” (IPD) meta-analizleri yapılmıştır. Önerilerin yeni çalışmaların sonuçları doğrultusunda belli aralıklarla güncellenmesi planlanmaktadır.Although brucellosis is very common in the world and Türkiye, there are no evidence-based guidelines to guide the diagnosis and treatment of the disease. This guide has been prepared by the Turkish Society of Clinical Microbiology and Infectious Diseases to provide evidence-based recommendations to physicians from different specialties interested in the diagnosis and treatment of brucellosis. The recommendations of the Clinical Practice Guide Development Guide of the Infectious Diseases Society of Amer- ica (IDSA) were taken as the basis for preparing this guide. The guideline preparation group determined 20 questions considered to be important in the diagnosis and treatment of brucellosis, and the publications that could answer these questions prepared in PICO (Population/Patient [P], Intervention [I], Comparison [C], Outcome [O]) format, were searched in ULAKBİM Tr Dizin, PubMed, Cochrane databases without date restrictions. The Grading of Recommen- dations, Assessment, Development, and Evaluation (GRADE) Working Group method was used to rank the evidence and determine the strength of the recommendations for each PICO question and for each individual outcome. Me- ta-analyses of comparative clinical studies were performed to answer the PICO questions. Individual participant data (IPD) meta-analyses with data obtained from case reports and case series were conducted in the absence of comparative clinical studies. It is planned to update the recommendations at regular intervals in line with the results of new studies

Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities

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Evaluation of Hepatoprotective Activity of Glycyrrhiza Glabra Linn on Paracetamol Induced Liver Damage in Rats

OBJECTIVE:Liver plays major role in detoxification and excretion of many endogenous and exogenous compounds, any injury to it or impairment of its functions may lead to many implications on ones health. Management of liver diseases is still a challenge to the modern medicine. Unfortunately, conventional or synthetic drugs used in the treatment of liver diseases are inadequate and sometimes can have serious side effects. In the absence of a reliable liver protective drug in modern medicine there are a number of medicinal preparations in ayurveda recommended for the treatment of liver disorders. In view of severe undesirable side effects of synthetic agents, there is growing focus to follow systemic research methodology and to evaluate scientific basis for the traditional herbal medicines that are claimed to possess hepatoprotective activity. Glycyrrhiza glabra Linn. (Family; Fabaceae) is a short lived, fast growing woody large herb. The green fruit contains papain similar to pepsin, pulp of the fresh fruit contain a soft yellow resin, fat, albuminoid sugar and pectin. Leaves contain an alkaloid called carpine and a glycoside named carposide. A properly ripened papaya is juicy, sweetish and somewhat like a cantaloupe in flavor. The fruits contain papain which helps in digestion and is used to tenderize meat. Fruit of Glycyrrhiza glabra Linn. is a rich source of vitamin C. It also contains vitamin E, pectin and carotinoids. Fruits, latex and juice of Glycyrrhiza glabra Linn. have been reported to be used in dyspepsia, intestinal irritation, habitual constipation and chronic diarrhoea. Traditionally, the leaf extract was used as a tonic for the heart, analgesia and treatment of stomachache. The extract is also known to have antioxidant properties. Glycyrrhiza glabra Linn. has been reported to be useful in liver ailments and has been shown to possess hepatoprotective activity against carbon-tetrachloride induced liver damage in experimental animals. But a systematic research on any possible effect of Glycyrrhiza glabra Linn. leaves on paracetamol induced hepatotoxicity seems to be scarce. Hence, it is decided to evaluate the hepatoprotective activity of Glycyrrhiza glabra Linn. leaves against paracetamol induced hepatotoxicity in albino wistar rats. CONCLUSION: In conclusion, the results of this study demonstrate that the methanol extract of Glycyrrhiza glabra Linn. leaves have a potent hepatoprotective action against paracetamol induced hepatic damage in rats. It’s mode in affording the hepatoprotective activity against paracetamol induced liver damage may be due to cell membrane stabilization, hepatic cell regeneration and enhancement of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase production. In spite of the unknown mechanism of action, the obvious hepatoprotective effect of Glycyrrhiza glabra Linn. leaves on paracetamol induced liver damage may have potential in clinical applications. The hepatoprotective and antioxidant potential of extract could have been brought about by various phytochemical principles i.e flavonoids, alkaloids, phenolics and tannins present in Glycyrrhiza glabra Linn. leaves

The Mechanistic Role and Therapeutic Potential of microRNA-122 in Alcoholic Liver Disease: A Dissertation

Chronic alcohol use results in accelerated liver injury, leading to alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, due to the complex nature of this disease process, a central, druggable mechanism has remained elusive. microRNAs are potent post-transcriptional regulators of gene expression. A single miRNA has the ability to regulate hundreds of pathways simultaneously, defining cellular fate and function. microRNA-122 (miR-122), the most abundant miRNA in hepatocytes, has a demonstrated role as an tumor suppressor, regulator of hepatocyte metabolism, and hepatic differentiation. In this dissertation I demonstrate the role of miR-122 on alcoholic liver disease (ALD) pathogenesis over four parts. In chapter II, I will demonstrate chronic alcoholic patients, free of neoplastic changes, have a reduction of miR-122 and that this miRNA regulates HIF-1α, a determinant of ALD pathogenesis. In chapter III, using hepatocytetropic adeno-associated virus 8 (AAV8) vector, I demonstrate that miR-122 inhibition mimics ALD pathogenesis, and furthermore, using hepatocyte-specific HIF-1α-null (HIF1hepKO) mice that this phenomenon is HIF-1α dependent. Given this finding, in chapter IV, I demonstrate that ectopic expression of miR-122 in vivo can reverse alcoholinduced liver damage, steatosis, and inflammation by directly targeting HIF-1α. Finally, in chapter V, I present evidence that alcohol-induced dysregulation of grainyhead-like proteins 1 and 2 (GRHL2), mediate the inhibition of miR-122 at the transcriptional level. These findings dissect a novel mechanistic regulatory axis of miR-122 and indicate a potential opportunity for restoration of miR-122 as a therapy in early ALD

Avaliação farmacológica dos efeitos hepáticos e gástricos da Baccharis trimera em lesões induzidas por etanol

Orientadoar : Profª. Drª. Alexandra AccoTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia. Defesa: Curitiba, 12/02/2016Inclui referênciasResumo: Estima-se que 2 bilhões de pessoas consumam o etanol em todo o mundo, e destas 76,3 milhões apresentam doenças relacionadas ao seu consumo. Dentre elas, a esteatose hepática alcoólica (EHA), estágio inicial das doenças hepáticas alcoólicas, destaca-se como uma enfermidade diretamente relacionada ao estresse oxidativo e a desarmonia da homeostase lipídica. Já a úlcera gástrica é uma doença multifatorial que decorre do desequilíbrio entre fatores agressivos e protetores. Tais lesões merecem atenção especial devido à ausência de tratamento preconizado, ou ainda, à vasta quantidade de efeitos colaterais observados. Buscando uma nova alternativa de tratamento, investigamos o potencial farmacológico da Baccharis trimera ("carqueja"), planta popularmente utilizada para tratar distúrbios gastrointestinais, em modelos de lesão gástrica e EHA. O extrato hidroetanólico (HEBT) foi obtido das partes aéreas da planta e caracterizado por cromatografia líquida de alta eficiência. Para investigar a atividade farmacológica do HEBT frente à EHA, submetemos camundongos à ingestão de etanol a 10% e dieta hipoprotéica por 6 semanas. Nas duas últimas semanas os animais foram tratados diariamente com o HEBT (30 mg.kg-1, via oral). O estresse oxidativo induzido pelo etanol foi revertido pelo HEBT, que normalizou os níveis de LPO, ROS total e GSH, bem como a atividade das enzimas SOD, Cat, GPx e GST. Além disso, o HEBT corrigiu os níveis de colesterol (CHO) e triglicerídeos (TG), HDL e LDL plasmáticos, normalizou os níveis de TG, HDL e LDL hepáticos e aumentou a excreção fecal de TG. O HEBT também reverteu alterações histológicas e ultraestruturais induzidas pelo etanol e normalizou a expressão dos genes Cyp2e1, Nrf2 e Scd1. Adicionalmente, úlceras induzidas por uso agudo ou crônico de etanol e por ácido acético, ligadura do piloro e motilidade gastrointestinal foram avaliados em ratos e camundongos a fim de examinar a atividade gastroprotetora do HEBT. O extrato preveniu a ulceração aguda e crônica, diminuindo significativamente a área da lesão induzida por etanol e ácido acético, mas não protegeu contra a depleção de muco. Além disso, o HEBT não alterou o volume e acidez gástricos. Histologicamente, o tratamento acelerou a cicatrização, refletida pela contração da base da úlcera. A atividade antiulcerogênica do HEBT pode ser atribuída, em partes, à inibição da geração de radicais livres e consequente prevenção da lipoperoxidação, promovida pelos ácidos cafeilquínicos, componentes principais do extrato. Nenhum sinal de toxicidade foi observado. Nossos resultados indicam que o HEBT possui efeitos hepato- e gastroprotetores e que pode ser uma terapia promissora para o tratamento de doenças hepáticas e gástricas decorrentes do consumo do etanol.Abstract: An estimated 2 billion people consume ethanol worldwide, and 76.3 million have ethanol-related disorders. Among them, alcoholic fatty liver disease (AFLD), early stages of alcoholic liver diseases, is directly related to oxidative stress and lipogenesis disruption. Regarding gastric ulcer, it is a multifactorial process that occurs through an imbalance between aggressive and protective factors. These injuries deserve special attention due the absence of preconized treatment, or even the vast amount of side effects observed. Searching for a new alternative treatment, we investigated the pharmacologic activity of Baccharis trimera ("carqueja"), a plant popularly used for gastrointestinal disorders, in gastric lesions models and AFLD. The hydroethanolic extract (HEBT) was obtained from the plant aerial parts and characterized by high-performance liquid chromatography. To investigate the pharmacologic HEBT activity against AFLD, we submitted mice to 10% ethanol ingestion and low-protein diet, during 6 weeks. In the last 2 weeks, mice were treated with HEBT (30 mg.kg-1, p.o.). The oxidative stress induced by ethanol was reversed by HEBT, which normalized LPO, total ROS and GSH levels, as well as SOD, Cat, GPx and GST activity. Beside this, HEBT corrected plasmatic cholesterol (CHO), triglycerides (TG), HDL and LDL levels, normalized hepatic TG, HDL and LDL levels and increased fecal TG excretion. HEBT also reverted histologic and ultrastructural alterations induced by ethanol and normalized Cyp2e1, Nrf2 e Scd1 gene expression. Additionally, gastric ulcers induced by acute or chronic ethanol or acetic acid consumption, pylorus ligature and gastrointestinal motility were evaluated in mice and rats to examine HEBT gastrointestinal protective effects. HEBT prevented acute and chronic gastric ulceration, decreasing significantly the lesion area induced by ethanol and acetic acid but not protect against mucus depletion. Besides this, HEBT did not altered gastric volume and acidity. Histologically, HEBT accelerated the healing, reflected by contractions of the ulcer base. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation, promoted by caffeoylquinic acids, the major components of extract. No signs of toxicity were observed. Our results indicate that HEBT have hepatic and gastroprotective effects and may be a promising therapy for hepatic and gastric disorders, due to ethanol consumption