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Lupine Publishers | ROS (Reactive Oxygen Species) and Nature

 Lupine Publishers | LOJ Pharmacology & Clinical Research

Abstract

Oxidative stress, defined as a disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defenses, is discussed in relation to its possible role in the production of tissue damage in diabetes mellitus. Important free radicals are described and biological sources of origin discussed, together with the major antioxidant defense mechanisms. Examples of the possible consequences of free radical damage are provided with special emphasis on lipid peroxidation. Ginger (Zingiber officinale), a member of the Zingiberaceae family, is a popular spice used globally especially in most of the Asian countries. Chemical analysis of ginger shows that it contains over 400 different compounds. The major constituents in ginger rhizomes are carbohydrates (50-70%), lipids (3-8%), terpenes, and phenolic compounds. Terpene components of ginger include zingiberene, β-bisabolene, α-farnesene, β-sesquiphellandrene, and α-curcumene, while phenolic compounds include gingerol, paradols, and shogaol. These gingerols (23-25%) and shogaol (18-25%) are found in higher quantity than others. Besides these, amino acids, raw fiber, ash, protein, phytosterols, vitamins (e.g., nicotinic acid and vitamin A), and minerals are also present. We selected its hypolipidemic and weight lost effects in primary and secondary hyperlipidemic patients. Type of Research study: It was placebocontrolled study. Area of research: Research was conducted in Jinnah hospital, Lahore, Pakistan. Duration of study: It was three months, from January 2018 to June 2018. Material, Method and Results: Already well understood, clearly explained written consent was taken from sixty hyperlipidemic patients age range from 18 to 70 years. Both gender male and female patients were enrolled. Patients were randomly divided in two groups, 30 patients were on drug ginger pasted-powder advised to take 5 grams in divided doses with their normal diet for the period of three months. Thirty patients were on placebo pasted-wheat powder, with same color as of ginger powder, advised to take 5 grams in divided doses with their normal diet for the period of three months. Their base line lipid profile and body weight was recorded at start of treatment and were advised to come for check-up, fortnightly. When duration of study was over, their lipid profile and body weight was measured and compared statistically with pre-treatment values. Three months treatment with 5 grams of Ginger decreased LDL-cholesterol 17.41%, total-cholesterol 8.83% and body weight 2.11%. When compared with placebo group, all changes in mentioned parameters were significant biostatistically. Conclusion: It was concluded from results of study that active ingredients of ginger lower plasma lipids and body weight significantly, eventually preventing development of coronary artery disease in primary and secondary hyperlipidemic patients.

Introduction

Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system’s ability to readily detoxify the reactive intermediates or to repair the resulting damage. Ginger is scientifically proved antioxidant agent. Ginger has been reported as a pain relief for arthritis, muscle soreness, chest pain, low back pain, stomach pain, and menstrual pain. It can be used for treating upper respiratory tract infections, cough, and bronchitis. As an anti-inflammatory agent, it is recommended for joint problems. Fresh juice of ginger has been shown to treat skin burns. Active component of ginger is used as a laxative and antacid medication. It is also used to warm the body for boosting the circulation and lowering high blood pressure. Because of its warming effect, ginger acts as antiviral for treatment of cold and flu. Ginger is also used as a flavoring agent in foods and beverages and as a fragrance in soaps and cosmetics. Cardiovascular diseases and stroke are complication of hyperlipidemia, diabetes mellitus, hypertension [1]. Many hypolipidemic drugs have already been proved to be useful in lowering serum lipid levels in patients.

However, its side effects in long term treatment were more reported and its prices were still expensive. Thus, efforts to develop effective and better hypolipidemic drugs had led to the discovery of natural medicinal herbs [2]. The beneficial uses of medicinal plants in traditional system of medicine of many cultures are extensively documented [3]. Several plants have been used as dietary adjuvant and in treating the number of diseases even without any knowledge on their proper functions and constituents [4]. Over 80% of the world population uses natural remedies as medicine and over 70% of doctors in Germany prescribe plant-based medicines [5]. Ginger (Zingiber officinale) is a natural dietary component, which has hypolipidemic, antiplatelet aggregation, antioxidant and anticarcinogenic properties [6]. Ginger is indigenous to southern China, spreading eventually to the Spice Islands, other parts of Asia and subsequently to West Africa and the Caribbean [7]. Ginger was exported to Europe via India in the first century AD as a result of the lucrative spice trade. India remains the largest producer of ginger [8]. Hypolipidemic and antiplatelet therapy is an effective approach for preventing coronary heart disease [9]. Ginger components are suggested as a potential new class of plateletactivation inhibitors without the potential side effects of aspirin, which is most commonly used in this approach. In a comparison of gingerols and analogs with aspirin, ginger compounds were found to be less potent compared to aspirin in inhibiting arachidonic acidinduced platelet release and aggregation and COX activity. However, several analogs had a significant inhibitory effect, suggesting that further development of more potent gingerol analogs might have value as an alternative to aspirin therapy in preventing ischemic heart disease [10,11]. Mechanism by which ginger may lower cholesterol is well understood by scientists and other researchers [12].

Material and Method

Research study was conducted at Jinnah hospital Lahore Pakistan, from January 2018 to June 2018. Written consent was taken from sixty hyperlipidemic patients age range from 18 to 70 years. Both gender male and female patients were enrolled. Patients were randomly divided in two groups, 30 patients were on drug ginger pasted-powder advised to take 5 grams in divided doses with their normal diet for the period of three months. Thirty patients were on placebo pasted-wheat powder, with same color as of ginger powder, advised to take 5 grams in divided doses with their normal diet for the period of three months. Their base line lipid profile (for total serum cholesterol, LDL-cholesterol ) and body weight was recorded at start of treatment and were advised to come for check-up, fortnightly. When duration of study was over, their lipid profile and body weight was measured and compared statistically with pre-treatment values. Serum total cholesterol was estimated by the enzymatic calorimatic method. Serum LDL-cholesterol was calculated by Friedwald formula (LDL-Cholesterol=Total Cholesterol-(Triglycerides/5 +HDL-Cholesterol). Body weight was determined by conventional method of usual weight machine Data were expressed as the mean ± SD and paired “t” test was applied to determine statistical significance as the difference. A probability value of <0.05 was considered as non-significance and P<0.001 was considered as highly significant change in the results.

Results

cholesterol from 185.21±2.01 to 157.72±1.90mg/dl, which is highly significant change in the parameter (p-value <0.001). Serum total cholesterol at baseline was 251.11±2.00mg/dl, which reduced to 230.71±1.77mg/dl. This change is highly significant statistically, with p-value <0.001. Mean body weight decreased from 79.01±kg to 77.32±2.61kg in three months therapy. All changes are highly significant statistically, having p-value <0.001. In placebo group LDL-Cholesterol, serum total cholesterol and body weight reduction was 0.18, 0.77, and 0.22 % respectively. All these changes are non-significant (p-value >0.05). Detailed changes are shown in following.

Key

If ± indicates standard error of mean, p-value >0.05 indicates non significant and P<0.001 indicates highly significant change in lipid profile. LDL-C means low density lipoprotein cholesterol 0mg/ dl, T-C means total serum cholesterol mg/dl, and body weight is measured in kg.

Discussion

Oxidative stress, defined as a disturbance in the balance between the production of reactive oxygen species (free radicals) and antioxidant defenses, is discussed in relation to its possible role in the production of tissue damage in diabetes mellitus, hyperlipidemia, hypertension etc. In our research study ginger was used in thirty male and female hyperlipidemic patients for three months, which reduced LDLcholesterol from baseline value of 185.21±2.01mg/dl to 157.72 ±1.90mg/dl. It is 17.4% change in this parameter, which is highly significant change statistically with p-value of <0.001. These results match with results of Bordia A [13] who mentioned that nearly same effects of ginger may be achieved when the drug is used for three months. He has mentioned detailed explanations regarding effects of ginger in hyperlipidemic and hyperglycemic conditions. These results are in contrast with study results of Thomson M [14] who observed less effect on LDL-cholesterol, i.e.; from 179.57±2.29mg/ dl to 176.92±2.11mg/dl when they used three grams of ginger for the period of 6 months in 82 hyperlipidemic subjects (Table 1).

 

These variations and too much contrast in these two comparable studies may be sample size, long duration of administration of chemical compound/drug. In our observation serum total cholesterol reduced from 251.11±2.00mg/dl to 230.71±1.77mg/ dl. Vaes LP and Chyka PA [15] observed almost same changes in serum total cholesterol when they used 2 grams ginger powder, twice daily for the period of one month. Their results augment and support results of our research work. Our results in the parameter also match with results of study conducted by Kubasek S [16] who observed same changes in serum total cholesterol (Table 2). Five grams of ginger in our study reduced body weight of 30 male/female patients from 79.01±kg to 77.32±2.61kg by 3 months therapy. Nurtjahja-Tjendraputra E [17] also observed same changes by their research study. This proves and augments our research results. Fuhrman B [18] described presence of various chemical ingredients in ginger which are responsible to decrease high levels of serum lipid levels and decreased blood pressure in hyperlipidemic patients. Our results are in contrast with study results of Guh J H [19] who proved that there is no significant effect on body weight when 2 grams of ginger powder daily was used for two months, in one hundred volunteers having secondary hyperlipidemia. Possible and guessed, scientific reason for this difference may be type of hyperlipidemia, ie; we included both primary and secondary hyperlipidemic patients, and they only included secondary hyperlipidemic patients.

 

https://lupinepublishers.com/pharmacology-clinical-research-journal/pdf/LOJPCR.MS.ID.000124.pdf

https://lupinepublishers.com/pharmacology-clinical-research-journal/fulltext/ros-(reactive-oxygen-species)-and-nature.ID.000124.php

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Wishing you a Magical and Blissful Holiday

 

May this Christmas end the year on a cheerful note and make way for a fresh and bright New year. Wishing you a magical and blissful holiday.

Lupine Publishers | Fasciola Hepatica Antioxidant System: Secretory Excretory System Proteins

 Lupine Publishers | LOJ Pharmacology & Clinical Research

Abstract

Fasciola hepatica is a trematode parasite with life cycle complex and as an intermediary it uses different species of snails, the most important is Lymnea truncatula. The definitive hosts being mainly ruminant mammals such as cows, sheep and even humans. The disease they produce is called fasciolosis and is more likely to find in warm to temperate climates with high humidity. It is an important parasitic problem in domestic animals and even in humans. This parasite lives in the bile ducts of several mammals. In order to survive in that environment, the parasite must survive to reactive oxygen species (ROS) of the host and those of its own metabolism. Here we review 3 antioxidant proteins of the parasite secretory excretory system and explain its possible mechanism of action. These proteins are: Thioredoxin peroxidase (TPx), Thioredoxin (TRX) and Thioredoxin glutathione reductase, considered a “general disulfide reductase”. The antioxidant detoxification system of the parasite is thus fully described.

Keywords: Fasciola hepatica; Antioxidant proteins; Secretory excretory system

Introduction

Fasciola hepatica is a hermaphrodite trematode parasite belonging to the platyhelminths’, which in its adult form is flattened, lanceolate, brown and measures approximately 3x1.5cm. It has a conical structure in the front end where it is called suction mouth oral and it has a ventral cup-shaped suction cup surrounded by muscle mass that allows it to adhere to the host (Figure 1). Its life cycle is complex and as an intermediary it uses different species of snails, the most important is Lymnea truncatula, the definitive hosts being mainly ruminant mammals such as cows, sheep and humans (Figure 2). The adult form of the parasite produces 3 to 5 thousand eggs per day which leave in the feces of the definitive host and develop at temperatures of 10 to 30 degrees Celsius in an aqueous environment. They hatch causing larvae called miracidia that look for the intermediate host within which they will go through the phases of sporocysts, redid mother, redid daughter and cercariae. The cercarias leave the intermediaries and encyst in plants as metacercarias waiting to be ingested by who will be their definitive host. The metacercarias are very resistant and can survive up to a year before entering the final host. Inside the definitive host they lodge in the bile ducts. The disease they produce is called fasciolosis and is more likely to find in warm and temperate climates with high humidity. It is an important parasitic problem in domestic animals and humans. They cause inflammation of the bile ducts and fibrosis, hypoalbuminemia, anemia and alteration of certain liver enzymes. Although the parasite lives in an anaerobic environment, oxygen is used for some metabolic processes, such as egg production, which generates many oxidizing molecules. Parasites to prevent damage by these oxidants, both those of their metabolism and those of the host organism’s metabolism, have developed a battery of antioxidant defenses that include enzymes that break down oxides and super oxides [1]. While more levels of defense possess a parasite, greater will be its survival within the host tissues. Helminth parasites in general have at least one of the 3 main antioxidant enzymes that are: superoxide dismutase, catalase and glutathione-dependent enzymes. In Fasciola no catalase has been found and it has low glutathione peroxidase activity [2], so it has other antioxidant enzymes. Fasciola hepatica has the following antioxidant enzymes and proteins, all present in the components of the excretory secretory extract which are part of a parasite detoxification system that allows its survival within the host [3,4]. Thioredoxin peroxidase (TPx), is a protein between 26 and 28 kDa which forms dimers and tetramers due to a cysteine residue conserved in position 47 that forms disulfide bridges and is possibly the primary site responsible for oxidation.

 

This protein has a protective activity against the inactivation of various enzymes by oxidation systems, but it is different from other TPxs from other parasites because in fasciola it works both in the presence of thiol and ascorbate groups, a relevant functional difference [5]. Another relevant fact and different from the other similar proteins of other parasites is that fasciola TPx has an extracellular location extending its protection against antioxidants to enzymes outside the parasite. The TPx mechanism could intervene in processes of protection of the inactivation of some membrane enzymes or exocellular parasite enzymes, making it possible to survive the host defense mechanisms [6,7]. Thioredoxin (TRX), representative protein of a group of widely distributed proteins that have dithiol-disulfide-oxidoreductase activity, its molecular mass is 12 kDa. Participates in important processes of metabolism and homeostasis. In the presence of TRX, the TPx protein protects enzymes more effectively against oxidation systems that employ DTT and / or ascorbate [6]. It is able to catalyze in vitro renaturation of both denatured insulin and RNase so it could be the natural physiological electron donor of the TPx protein [4]. It participates in the electron transfer pathway through the reversible oxidation of two neighboring cysteines in a biochemical cycle that involves TRX reductase and NADPH [8,9]. Finally, Thioredoxin glutathione reductase, considered as a “general disulfide reductase” is involved in the reduction of exposed disulfide bonds of a variety of proteins and thus the entire system is able to metabolize H2O2 and other alkyl peroxides [10]. With this protein the antioxidant system of detoxification of the parasite is completed whose proposed model is as follows: TPx protects against ROS inactivation in an oxidation system catalyzed by Fe3 + using thiol and / or ascorbate.

Conclusion

The reducing agent is responsible for activating the enzyme by reducing disulfide bridges. Oxidized sulfhydryl groups are regenerated by transferring reducing agents from NADPH to thioredoxin reductase, from it to thioredoxin and finally to TPx as shown in the (Figure 3) [4]. It does not seem logical to think that NAPH acts extracellularly as a source of the necessary reducing power. Therefore, the theory of acting inside the cell is postulated, so that proteins could be secreted in a reduced state. Thus, the parasite defense system against ROS products (reactive oxygen species) generated by the host’s immune response and by the parasite’s own metabolism is described.

 

https://lupinepublishers.com/pharmacology-clinical-research-journal/pdf/LOJPCR.MS.ID.000123.pdf

https://lupinepublishers.com/pharmacology-clinical-research-journal/fulltext/fasciola-hepatica-antioxidant-system-secretory-excretory-system-proteins.ID.000123.php

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