Oxidative stress and antioxidants in diabetes mellitus

Numerous studies have implicated oxidative stress in the development of complications of diabetes. During hyperglycemia, production of oxidant agents such as reactive oxygen species and reactive nitrogen species increases. This process, along with a decrease in the activity of antioxidant enzymes, induces oxidative stress in the body. This redox imbalance causes damage to vital biomolecules such as proteins, lipids and DNA and results in the generation of harmful products for the body. Mechanisms associated with the creation of oxidative stress conditions and subsequently complications of diabetes are explained through several pathways such as flux through the polyol pathway, intracellular production of advanced glycation end products precursors, protein kinase-C activation, and increased activities of the hexosamine pathway. On the other hand, the study of polymorphism in the antioxidant enzymes genes indicates that some of the gene polymorphisms reduce the antioxidant power of the enzymes. This article aims to review various studies to demonstrate the effect of oxidative stress on the pathogenesis of diabetes and the positive role of antioxidants on diabetic complications. Ghasemi-Dehnoo Maryam 1 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord Amini-Khoei Hossein 2 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord Lorigooini Zahra 3 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord Rafieian-Kopaei Mahmoud 4 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord Braun S, Bitton-Worms K, LeRoith D. The link between the metabolic syndrome and cancer. Int J Biol Sci 2011; 7(7): 1003-1015. Sagoo MK, Gnudi L. Diabetic nephropathy: Is there a role for oxidative stress. Free Radic Biol Med 2018; 116: 50-63. Rani V, Deep G, Singh RK, Palle K, Yadav UCS. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci 2016; 148: 183-193. Hutcheson R, Rocic P. The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: The great exploration. Exp Diabetes Res 2012; 2012: 1-13. Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-a concise review. Saudi Pharm J 2016; 24(5): 547-553. Calderon GD, Juarez OH, Hernandez GE, Punzo SM, De la Cruz ZD. Oxidative stress and diabetic retinopathy: Development and treatment. Eye 2017; 31(8): 1122-1130. Nunes S, Rolo AP, Palmeira CM, Reis F. Diabetic cardiomyopathy: Focus on oxidative stress, mitochondrial dysfunction and inflammation. In: Kirali K. (eds.) Cardiomyopathies-types and treatments. Croatia: InTech; 2017, p. 235-257. Rahimi-Madiseh M, Malekpour-Tehrani A, Bahmani M, Rafieian-Kopaei M. The research and development on the antioxidants in prevention of diabetic complications.

Brucellosis: Pathophysiology and new promising treatments with medicinal plants and natural antioxidants

Brucellosis is an old, infectious and common zoonosis whose causative agents are Gramnegative bacteria from the Brucella genus. Brucellosis is transmitted through direct contact with infected animals or using unpasteurized dairy products of goats, pigs, camels, sheep, buffalo and cows. Brucellosis is still the most common zoonosis in the world, with most of cases occurring in developing countries. Today, an approach to traditional medicine and medicinal plants, especially with regards to the repeated recommendations of the World Health Organization, is a necessity. One-third of chemical drugs are produced by using plants and there is a high potential to produce more drugs from plants. Medicinal plants are helpful in the management of various conditions, especially bacterial diseases. Although there is not enough scientific evidence regarding the clinical effectiveness of herbal drugs for the treatment of brucellosis, there is strong evidence on the antimicrobial effects of herbal drugs to prevent infection. Therefore, this article seeks to describe the antibacterial effects of some plant-derived essential oils or extracts, so that they can serve as promising choices to develop new anti-Brucella medications, as suitable alternatives to conventional antibiotics for brucellosis, as much as possible, taking into account the benefits of these herbal drugs.

The research and development on the antioxidants in prevention of diabetic complications

Diabetes mellitus can damage the eyes, kidneys, nerves and heart. Microvascular and macrovascular disorders are the leading causes of morbidity and mortality in diabetic patients. Hyperglycemia can increase the indicators of lipid peroxidation and oxidative stress in which free radicals have the main role in the pathogenesis of these complications. Therefore, antioxidants which combat oxidative stress should be able to prevent and repair free radicals induced damages. Although free radicals contribute to kidney damage, atherosclerosis, diabetes, heart disease, nephrotoxicity and hepatotoxicity; however, clinical trials do not uniquely confirm a substantial impact on diabetic damage. It seems that antioxidants in vegetables, fruits and grains help preventing diabetes complications; however, there is little evidence that taking single antioxidants such as vitamin E or vitamin C protect these complications. The findings about combination antioxidants are also complicated and not entirely clear. In this review paper we tried to present the role of oxidative stress on micro-vascular complications of type 2 diabetes mellitus. Other objective of this paper is to review the new findings about the role of various antioxidants on prevention and treatment of diabetes mellitus as well as its complications including retinopathy, nephropathy and neuropathy.

The research and development on the antioxidants in prevention of diabetic complications

Diabetes mellitus can damage the eyes, kidneys, nerves and heart. Microvascular and macrovascular disorders are the leading causes of morbidity and mortality in diabetic patients. Hyperglycemia can increase the indicators of lipid peroxidation and oxidative stress in which free radicals have the main role in the pathogenesis of these complications. Therefore, antioxidants which combat oxidative stress should be able to prevent and repair free radicals induced damages. Although free radicals contribute to kidney damage, atherosclerosis, diabetes, heart disease, nephrotoxicity and hepatotoxicity; however, clinical trials do not uniquely confirm a substantial impact on diabetic damage. It seems that antioxidants in vegetables, fruits and grains help preventing diabetes complications; however, there is little evidence that taking single antioxidants such as vitamin E or vitamin C protect these complications. The findings about combination antioxidants are also complicated and not entirely clear. In this review paper we tried to present the role of oxidative stress on micro-vascular complications of type 2 diabetes mellitus. Other objective of this paper is to review the new findings about the role of various antioxidants on prevention and treatment of diabetes mellitus as well as its complications including retinopathy, nephropathy and neuropathy.

Neural mechanisms underlying morphine withdrawal in addicted patients: a review

Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal

Protection of renal tubular cells by antioxidants: current knowledge and new trends

Acute renal damage mainly develops following toxic or ischemic insults and is defined as acute. These damages have largely been attributed to oxidative stress. Recently much attention has been directed toward decreased renal tubular cell regeneration during tubular cell injury. Antioxidants have recently been the focus of researchers and scientists for prevention and treatment of various oxidative stress-related conditions, including renal toxicities. Although free radicals are known to contribute in kidney injury and abundant researches, particularly laboratory trials, have shown the beneficial effects of antioxidants against these complications, long term clinical trials do not uniformly confirm this matter, especially for single antioxidant consumption such as vitamin C. The aim of this paper is to discuss the possible explanation of this matter

role of Th1 and Th17 cells in glomerulonephritis

Thelper [Th] cells as an important part of the immune is responsible for elimination of invading pathogens. But, if Th cell responses are not regulated effectively, the autoimmune diseases might develop. The Th17 subset usually produces interleukin-17A which in experimental models of organ-specific autoimmune inflammation is very important. Directory of open access journals [DOAJ], Google Scholar, Embase, Scopus, PubMed and Web of Science have been searched. Fifty-six articles were found and searched. In the present review article, we tried to summarize the recently published data about characteristics and role of Th1 and Th17 cells and discuss in detail, the potential role of these T helpers immune responses in renal inflammation and renal injury, focusing on glomerulonephritis. Published papers in animal and human studies indicated that autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, classically believed to be Th1-mediated, are mainly derived from a Th17 immune response. Identification of the Th17 subgroup has explained seemingly paradoxical observations and improved our understanding of immune-mediated inflammatory responses. Secretion of IL-17A, as well as IL-17F, IL-21, IL-22, suggests that Th17 subset may play a crucial role as a pleiotropic pro-inflammatory Th subset. There is experimental evidence to support the notion that Th1 and Th17 cells contribute to kidney injury in renal inflammatory diseases like glomerulonephritis

Inhibitory effect of Thymus vulgaris extract on memory impairment induced by scopolamine in rat

Objective: To investigate the effect of Thymus vulgaris (. T. vulgaris) on learning and memory functions in scopolamine-induced memory deficit in rats. Memory enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the Morris water maze and passive avoidance paradigm. Methods: A total of 42 male Wistar rats were divided into 6 equal groups as follow: control group: received water, scopolamine treated group: received scopolamine 1 mg/kg for 15 days, two scopolamine + T. vulgaris treated groups: received scopolamine and T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days, two intact groups: received T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days. Results: Administration of T. vulgaris extract significantly restored memory and learning impairments induced by scopolamine in the passive avoidance test and Morris water maze test. Conclusions: T. vulgaris extract has repairing effects on memory and behavioral disorders produced by scopolamine and may have beneficial effects in the treatment of Alzheimer's disease.

Identification of medicinal plants effective in infectious diseases in Urmia, northwest of Iran

Objective: To identify the medicinal plants effective in infectious diseases. Methods: Initially, we obtained a list of herbalists and traditional healers from Food and Drug Deputy. Direct observations and interviews as well as collection of herbarium specimens of indigenous medicinal plants effective in infectious diseases of urinary tract, reproductive, digestive, respiratory and skin systems were performed. This study was conducted through questionnaires and interviews; the questionnaires were distributed among traditional healers and simultaneous interviews were also run. The plants were herbariumized, herbarium specimens were authenticated, and their species were determined by using reliable flora and other sources. Finally, the data were input into Excel 2010 and analyses were performed. Results: Out of the studied plants, 35 native medicinal plants belonging to 17 families were effective in the treatment of various diseases and infections. In this study, the Lamiaceae family had the highest frequency of plants for the treatment of infections. Traditional healers of Urmia in 24% of cases used the leaves of medicinal herb to treat patients. In 68% of cases, they prescribed medicinal herbs in the boiled forms. Most medicinal herbs showed therapeutic effect on the digestive system. Conclusions: Traditional medicinal sources, valuable knowledge of traditional healers in Urmia, the scientific investigation of the effects of the herbs offered in this study and their effects in traditional medicine may provide a good source for new drugs in modern medicine.

Effects of Matricaria chamomilla extract on motor coordination impairment induced by scopolamine in rats

Objective: To evaluate the effect of ethanolic extract of chamomile on balance and motor learning in rats receiving scopolamine and intact rats. Methods: Fourty-two rats were divided into 6 groups ( n = 7). Control group received distilled water. Rats in Group 2 were given 1 mg/kg scopolamine. Groups 3 and 4 received chamomile extract 200 mg/kg and 500 mg/kg, respectively, and scopolamine simultaneously for 20 days. Intact groups (Groups 5 and 6) only received chamomile extract 200 mg/kg and 500 mg/kg, respectively. Motor coordination of rats was assessed with rotarod apparatus. Results: According to the obtained results, compared with the control group, scopolamine significantly decreased time spent on rotarod performance (. P < 0.001). Compared with scopolamine group, the strength and staying on rotarod apparatus in Group 3 significantly increased ( P < 0.05). The results of this research showed that intact groups that received only chamomile extract at doses of 200 mg/kg and 500 mg/kg significantly increased time spent on rotarod, compared with scopolamine group ( P < 0.001). Conclusions: The results of this study indicated the high antioxidant property and protective effect of chamomile extract on motor coordination in the groups that received scopolamine.

Medicinal plants with hepatoprotective activity in Iranian folk medicine

There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for liver. In this review, we have introduced some medicinal plants that are used mainly for the treatment of liver disorders in Iranian folk medicine, with focus on their hepatoprotective effects particularly against CC14 agent. In this study, online databases including Web of Science, PubMed, Scopus, and Science Direct were searched for papers published from January 1970 to December 2013. Search terms consisted of medicinal plants, traditional medicine, folk medicine, hepatoprotective, Iran, liver, therapeutic uses, compounds, antioxidant, CC14, anti-inflammatory, and antihepatotoxic, hepatitis, alone or in combination. Allium hirtifolium Boiss., Apium graveolens L., Cynara scolymus, Berberis vulgaris L., Calendula officinalis, Nigella sativa L., Taraxacum officinale, Tragopogon porrifolius, Prangos ferulacea L., Allium sativum, Marrubium vulgare, Ammi majus L., Citrullus lanatus Thunb, Agrimonia eupatoria L. and Prunus armeniaca L. are some of the medicinal plants that have been used for the treatment of liver disorders in Iranian folk medicine. Out of several leads obtained from plants containing potential hepatoprotective agents, silymarin, β-sitosterol, betalain, neoandrographolide, phyllanthin, andrographolide, curcumin, picroside, hypophyllanthin, kutkoside, and glycyrrhizin have been demonstrated to have potent hepatoprotective properties. Despite encouraging data on possibility of new discoveries in the near future, the evidence on treating viral hepatitis or other chronic liver diseases by herbal medications is not adequate.

Leishmaniosis phytotherapy: Review of plants used in Iranian traditional medicine on leishmaniasis

Many native plants in traditional medicine have been used for the treatment of cutaneous leishmaniasis and the recent clinical trials have proven the efficacy of some of them. Researches conducted on these plants have shown that garlic, shallots, wormwood, yarrow, walnuts, thyme, henna plant, mimosa, aloe, wood betony, medlar, periwinkle, yeah, savory, black beans, etc. are effective on cutaneous leishmania. Synthetic agents in Iranian market have some disadvantages such as high cost and side effects and are painful in injections. Given the effectiveness of these plants, they can be a source of natural and safe compounds for the treatment of Leishmania. Therefore, more clinical researches should be done to determine the effectiveness and safety of these medicinal plants, their active ingredients and their possible toxic substances which can lead to the production of effective and safe drugs for leishmaniasis. It also might be an effective way to prepare herbal ointment on wound healing.

Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine

<p><b>OBJECTIVE</b>To evaluate the effects of berberine (BBR) on the liver phosphatidate phosphohydrolase (PAP) and plasma lipids in rats fed on high lipogenic and normal diet.</p><p><b>METHODS</b>Forty rats were randomly divided into 5 groups. Group I (control) received standard diet. Group II received standard diet plus 90 mg/kg BBR and Groups IV received lipogenic diet (containing sunflower oil, cholesterol and ethanol) without treatment. Groups III and V received lipogenic diet plus 90 mg/kg BBR and 30 mg/kg gemfibrozil, respectively. On Day 60 of the experiment, blood samples were collected and PAP, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, very low density lipoprotein, malondialdehyde, plasma antioxidant, and liver histopathology assessments were conducted.</p><p><b>RESULTS</b>PAP, plasma triglyceride, total cholesterol, very low density lipoprotein, and malondialdehyde levels decreased significantly (P<0.05) in Group III compared to Group IV (24.94%, 36.11%, 21.18%, 36.86% and 19.59%, respectively). The liver triglyceride and cholesterol in Groups III and V had a remarkable decrease (P<0.001) compared with Group IV (24.94% and 49.13%, respectively). There was a significant reduction (P<0.05) in atherogenic index in Groups III compared with Group IV.</p><p><b>CONCLUSIONS</b>These results clearly suggested that BBR could be effective in reducing liver PAP, lipid abnormality, liver triglyceride and lateral side effects of hyperlipidemia.</p>

Ameliorative effect of melatonin against contrast media induced renal tubular cell injury

Reactive oxygen species [ROS] is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against the nephrotoxicity of contrast media. In an experimental study 40 adult male Wistar rats were randomly divided into four equal groups including: 1] Control group [No drug], 2] Contrast media group [10 ml/kg iodixanol i.v. single dose], 3] Contrast media and melatonin [first 10 ml/kg iodixanol then 10 ml/kg/day melatonin by i.p. injection on days 3, 4 and 5] and 4] Contrast media and melatonin pretreatment group [melatonin 10 ml/ kg/day by i.p. injection on 1, 2 and 3 days, then 10 ml/kg iodixanol by i.v. injection on third day. The blood creatinine and BUN as well as the histological changes were evaluated for severity of renal injury [degeneration, vacuolization of tubular renal cells, dilatation of tubular lumen and presence of debris in the lumens], by scoring from one to four. Contrast media significantly increased the creatinine and BUN and renal injury [p < 0.05]. Melatonin prevented and reversed the injury induced by contrast media [P < 0.05]. Pretreatment with melatonin reduced the renal injury induced by contrast media [P < 0.05]. Melatonin is an effective drug to prevent contrast-induced renal injury. Therefore its usage [especially pretreatment] might be beneficial in patients who are planning to use contrast media agents

vitro impact of hydro-alcoholic extract of rosa damascena mill on rat ileum contractions and the mechanisms involved

The petal's hydro-alcoholic extract of Rosa damascene Mill. on ileum contractions of Wistar rats and its possible mechanism were investigated. Forty-eight male Wistar rats were divided into six groups. Ileum was placed adjacent to propranolol [1 microM], naloxone [1 microM] and L-NAME [100 microM] and also under the influence of different doses [2-8 mM] of calcium chloride. Cumulative extract of R. damascene Mill. [100, 500, and 1000 mg/L] decreased ileum contractions induced by KCl [60 mM] in a dose-dependent manner [P < 0.0001]. Propranolol and naloxone significantly decreased the inhibitory effect of the extract on contractions induced by KCl [P < 0.001], but L-NAME was ineffective. Furthermore, calcium led to the contraction of depolarized tissue through KCI and this contractile effect decreased significantly induced by the cumulative concentrations of the extract [P < 0.001]. The results indicate that R. damascene Mill. Dose-dependently [100, 500, and 1000 mg/L] decreases ileum movements of the rat probably through stimulating the beta-adrenergic and opioid receptors and voltage-dependent calcium channels, and it may be used to treat digestive disorders

Effect of dietary ethanolic extract of lavandula officinalis on serum lipids profile in rats

Antioxidants are effective in prevention and treatment of cardiovascular diseases. Lavandula officinalis possesses antioxidant activity, therefore, in this study; the effects of Lavandula officinalis extract were investigated on serum lipids levels of rats. Experimental mature male Wistar rats were treated with 100, 200 or 400 mg/Kg/day of lavender ethanolic extract or distilled water for 25 days via gastric gavage [n=8 each group]. At the end of 25[th] day, the serum cholesterol, triglyceride, HDL, LDL and VLDL levels, as well as atherogenic indices were determined in rats' serum. The ethanolic extract of lavender decreased serum cholesterol, triglyceride, LDL and VLDL levels in 100 mg/Kg group [p=0.03, p=0.001, p=0.001, p=0.001, respectively]. Serum HDL level increased in 100 mg/Kg/day group [p=0.01]. Lavender extract decreased LDL/HDL level at doses of 100 and 200 mg/Kg/day [p=0.001, p=0.001, respectively]. The TG/HDL levels decreased in experimental groups with doses of 100 and 200 mg/Kg/day [p=0.001, p=0.001, respectively]. Lavandula officinalis extract exerts hypolipidemic effect in rats and might be beneficial in hyperlipidemic patients