Free Radical-induced Tissue Damage Research Articles

Biomolecular Protective Effects of Bacopa Monnieri (L.) Pennell Leaf Extracts Against Oxidative Damage

In living systems, free radicals are constantly generated and they can cause extensive damage to tissues and biomolecules, leading to various disease conditions, especially degenerative diseases, and extensive lysis.The most effective way to eliminate free radicals which cause oxidative stress is with the help of antioxidants. Antioxidants prevent free radical-induced tissue damage by preventing the formation of radicals by scavenging them, or by promoting their decomposition. In the present study, the biomolecular protective effects of B. monnieri leaf extracts against oxidative stress induced damage to lipids and DNA in cell free systems and intact cells were analyzed. Results showed that the leaf extracts of B. monnieri rendered protection against oxidative stress induced damage in both cell-free systems and intact cells. Bangladesh J. Bot. 51(1): 123-129, 2022 (March)

In vitro study on the antioxidant activity of methanolic leaf extract of Carica papaya

Background: Newer drug research worldwide is now focusing on medicinal plants for ensuring health and vitality due to the seemingly safer side effect profile and abundance of plants in nature, compared to synthetic drugs. Antioxidants are vital in preventing free radical induced tissue damage. The purpose of the present study is to evaluate the antioxidant activity of the methanolic extract of the leaves of Carica papaya using 1,1-diphenyl-2-picrylhydrazine (DPPH). Phytochemical tests proved the presence of bioactive ingredients in the extract.Methods: DPPH free radical assay, one of the most accurate methods for evaluating antioxidant activity, was used to evaluate the antioxidant activity of methanolic extract of leaves of C. papaya.Results: The methanolic leaf extract of C. papaya showed antioxidant property with free radical scavenging activity increasing with increase in concentration. The IC50 value of methanolic extract was 213.68 µgm/ml. Ascorbic acid was used as control.Conclusions: Oxidative stress has been linked to heart disease, cancer, immune deficiency. Antioxidants as suggested from various studies may reduce the risk of such diseases. The utility of C. papaya in the treatment of heart disease, cancer and immune deficiency will have to be proved by detailed evaluation of its pharmacological properties.

The role of rutin and diosmin, two citrus polyhydroxyflavones in disease prevention and treatment

Chronic inflammation and dysregulation of apoptotic pathways leading to free radical-induced tissue damage are widely recognized as major underlying causes of major degenerative diseases, including cancer, diabetes, neurological and cardiovascular disorders. Citrus fruits are rich sources of polyphenolic flavonoids well known for their wide range of pharmacological properties. Rutin (quercetin-3-O-rutinoside) and diosmin (diosmetin 7-Orutinoside) are two major polyhydroxyflavone glycosides abundantly found in citrus peels and, to a lesser extent, in pulp of a variety of different citrus species. During digestion, hydrolysis by intestinal enzymes and gut microbiota lead to the release of their corresponding bioactive aglycones (e.g., quercetin or diosmetin). Data obtained in cell-based, animal and clinical studies demonstrated strong preventive and/or therapeutic effects of rutin and its aglycone flavone quercetin. Although lesser studies available, our recent literature review suggests diosmin as promising citrus fruit polyhydroxyflavonoids, effective against various diseases associated with chronic inflammation.

Coenzyme Q10 and fish oil synergistically alleviate aluminum chloride-induced suppression of testicular steroidogenesis and antioxidant defense

Aluminum (Al) is an environmental xenobiotic that stimulates free radical generation and hence reproductive toxicity. Coenzyme Q10 (CoQ10) effectively counteracts free radical-induced tissue damage. Omega-3 polyunsaturated fatty acids present in fish oil (FO) exert beneficial effects on reproduction in male animals. This study therefore investigated the effects of both agents on testicular dysfunction induced by aluminum chloride (AlCl3). Fifty male rats were gavaged with either 1% gum acacia (control group) or AlCl3 (34 mg/kg/day) for ten weeks. Concurrently, AlCl3-treated rats received no treatment, CoQ10 (10 mg/kg/day, p.o.), and/or FO (400 mg/kg/day, p.o.) for ten weeks. AlCl3 caused a significant decrease in serum testosterone, luteinizing hormone (LH), and follicular stimulating hormone (FSH), as well as testicular weight, antioxidant enzyme gene expression and activities, reduced glutathione, zinc, adenosine 3′,5′-cyclic monophosphate (cAMP) contents, and number of Leydig cells, along with down-regulation of 3beta-hydroxysteroid dehydrogenase (3β-HSD), 17β-HSD, steroidogenic acute regulatory protein (STAR), and cholesterol side-chain cleavage enzyme (P450scc) gene expression. However, testicular Al, malondialdehyde (MDA), and nitric oxide (NO) levels were markedly increased. Treatment with CoQ10 and FO, alone or in combined form led to an improvement in the aforementioned biomarkers. Overall, individual or combined treatment with CoQ10 and FO could ameliorate the toxic effects of AlCl3 on testicular tissues by mechanisms related to their potent antioxidant potential and stimulatory effects on steroidogenic enzymes transcription. CoQ10 seems to be better than FO regarding oxidative and nitrosative stress, Zn deficiency, and Al overload. However, FO showed more pronounced effect than CoQ10 on hormones, steroidogenic markers, and cAMP. A cocktail of both demonstrated greater protective effects on testicular tissues than monotherapy.

Interaction Of Propylthiouracil With Model Systems Generating A Superoxide Radical

Summary Propylthiouracil is used against Grave's Disease and for developing animal models of hypothyroidism. Apart from depressed metabolism, free radical-induced tissue damage has been registered as an effect from this drug. Superoxide is essential for generation of free radicals in tissues. The mutual effects of Propylthiouracil and superoxide radical have not been well investigated. The in vitro effects of Propylthiouracil on the free radicals in three model systems generating superoxide were measured using luminol-dependent chemiluminescence and spectrophotometry. The drug did not affect the formation of free radicals in the presence of potassium superoxide and in pyrogallol-oxygen solutions, while in the presence of the xanthine/xanthine oxidase system a distinct prooxidant effect was registered. The investigation of the system propylthiouracil/xanthine oxidase showed mild free radicals formation along with decreasing intensities of the drug's UV-specter. Our in vitro investigation indicated that, along with the transformation of xanthine to uric acid over xanthine oxidase, some free radicals may be produced due to the interaction of propylthiouracil with the enzyme. It was proposed that this might contribute to the in vivo free radicals-induced tissue damage observed in the presence of propylthiouracil.

Protective effect of CardiPro against doxorubicin-induced cardiotoxicity in mice

The effect of CardiPro, a polyherbal formulation, with an antioxidant property, has been studied on doxorubicin (DXR)-induced cardiotoxicity in mice. CardiPro (150 mg/kg b.w., twice daily was administered orally for 7 weeks along with four equal injections (each containing 4.0 mg/kg b.w., DXR) intraperitoneally, once weekly (cumulative dose 16 mg/kg). After a 3-week post DXR treatment period, cardiotoxicity was assessed by noting mortality, volume of ascites, liver congestion, changes in heart weight, myocardial lipid peroxidation, antioxidant enzymes and histology of heart. DXR-treated animals showed higher mortality (50%) and more ascites. Myocardial SOD and glutathione peroxidase activity were decreased and lipid peroxidation was increased. Histology of heart of DXR-treated animals showed loss of myofibrils and focal cytoplasmic vacuolization. CardiPro significantly protected the mice from DXR-induced cardiotoxic effects as evidenced by lower mortality (25%), less ascites, myocardial lipid peroxidation, normalization of antioxidant enzymes and minimal damage to the heart histologically. Our data confirm the earlier reports that DXR cardiotoxicity is associated with the free radical-induced tissue damage. Administration of CardiPro, with an antioxidant property, protected the DXR-induced cardiotoxicity in mice.

Plasma Uric Acid Levels in Women With Cervical Intraepithelial Neoplasia

: The objective of this study was to determine the association of plasma levels of uric acid, an endogenous antioxidant, in women with cervical intraepithelial neoplasia (CIN), while controlling for the confounding effects of human papillomavirus (HPV) infection, age, smoking, and use of oral contraception. Plasma-reduced and oxidized uric acid levels were determined in 650 women by high-performance liquid chromatography, employing electrochemical technique. The findings demonstrated that 1) plasma-reduced uric acid (PRUA) levels in women with CIN (n = 311) were significantly lower (P < 0.05) compared with women in a control group (n = 339); 2) according to multiple logistic regression analysis, PRUA levels were negatively (P = 0.0113) and HPV infection were positively associated (P < 0.0001) with CIN, after controlling for the confounding effects of the studied factors; 3) according to multiple regression analysis, there was a 31% decrease in CIN risk for each incremental increase of 1mg/dl of PRUA; and 4) according to polychotomous logistic regression analysis, independent of HPV infection, PRUA level was inversely associated with the histopathological graded severity of CIN. We have previously reported decreased plasma levels of exogenous antioxidants, for example, vitamins C and E, in women with CIN independent of HPV infection. The data suggest that plasma deficiencies of several antioxidants in HPV-infected uterine cervical tissue may create an oxidative environment that renders the tissue susceptible to free radical damage. It may be speculated that chronic free radical-induced tissue damage in the context of persistent HPV infection may be involved in the pathogenesis of CIN.

Effect of melatonin on the malondialdehyde level of neutrophils in cyclosporine-treated rats

Introduction Cyclosporine (CsA) may contribute to oxygen free radical metabolism in neutrophils, thus resulting in the damage to these cells. This damage may be mitigated by antioxidants such as melatonin. In this study, we measured the malondialdehyde level, which was used as a marker of free radical–induced tissue damage from neutrophils in rats treated with CsA and melatonin. Methods The experiments included the following: (1) normal controls (group 1) that received Cremophor EL and 0.5 mL of 5% ethanol-saline solution; (2) CsA alone–treated (group 2) rats that received 15 mg/kg of body weight per day for 14 days by subcutaneous injection; and (3) melatonin-treated (group 3) rats received CsA as for group 2 plus melatonin (715 μg). Results Malondialdehyde level was significantly higher among group 2 (13.34 ± 7.54 nmol/10 7 neutrophils) than group 1 animals (7.33 ± 2.63 nmol/10 7 neutrophils; P < .05). The level was significantly lower in group 3 (5.58 ± 1.59 nmol/10 7 neutrophils) than group 2 ( P < .01). CsA levels were not significantly different between group 2 (6.25 ± 1.60 μg/mL) and group 3 (6.09 ± 2.01 μg/mL). Conclusions In this experiment, the malondialdehyde level in neutrophils was increased after CsA treatment, suggesting that damage resulted from oxygen free radicals by CsA. This damage was reduced by melatonin. Thus, CsA-induced neutrophils oxidative damage may be protected by melatonin in transplant recipients.

Phospholipid plasmalogen, a surrogate marker of oxidative stress, is associated with increased cardiovascular mortality in patients on renal replacement therapy

There is a high incidence of premature cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). Free radical-induced tissue damage is thought to play a major role in the pathogenesis of atherosclerosis, and there are several reports indicating an increased oxidative stress in ESRD. However, it is not well established that increased oxidative stress predicts cardiovascular mortality in ESRD. Plasmalogens, a group of phospholipids with a vinyl ether bond in the sn-1 position, are considered to be sensitive markers of oxidative stress. Cardiovascular and non-cardiovascular mortality was recorded (follow-up time 1860+/-94 days) in 105 ESRD patients (mean age 51+/-2 years) in whom the fasting ratio of the erythrocyte levels of plasmalogens (DMA 16/C16:0 and DMA 18/C18:0) had been determined at the start of renal replacement therapy (RRT). The prevalence of malnutrition (subjective global assessment), diabetes mellitus (DM), smoking habits and CVD was also determined. Thirty-eight patients who died of CVD (0.066+/-0.003) had a significantly lower DMA 16/C16:0 ratio than 15 patients who died of non-cardiovascular causes (0.078+/-0.005; P<0.05) and 52 patients alive at follow-up (0.075+/-0.003; P<0.05). A Cox proportional hazard model analysis showed that a low (<median) DMA 16/C16:0 ratio at the start of RRT was associated (relative risk 1.50; confidence interval 1.07-2.16; P<0.05) with CVD mortality independently of age, gender, DM and CVD. These results suggest that increased oxidative stress may be a risk factor for cardiovascular mortality in ESRD.

Malondialdehyde and antioxidant enzymes in children with obstructive adenotonsillar hypertrophy

Objective: Free radical induced tissue damage has been implicated in the pathogenesis of several diseases. We aimed to investigate the role of free radicals and scavenging enzymes in children with obstructive adenotonsillar hypertrophy. Materials and methods: The study consisted of 29 children with obstructive adenotonsillar hypertrophy and 51 control subjects with similar age and sex. All the patients and/or their parents had complaints of snoring, mouth breathing, and pausing of breath during sleep for at least 6 months. All patients underwent an adenotonsillectomy operation under general anesthesia with curettage and cold dissection methods. Venous blood was taken preoperatively and 4 weeks postoperatively. After collection of blood samples into citrate (3.5 mg/ml blood) containing glass tubes, erythrocyte sediments were prepared for the analyses. Then malondialdehyde (MDA) level, and superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities were measured. Results: The levels of MDA and activities of SOD and GSHPx were significantly higher in the pre-tonsillectomy period than in the post-tonsillectomy period. However, CAT activity was not different in pre- and postoperative period. Conclusion: Our study supports the notion that oxidant and antioxidant defense mechanisms are altered in children with obstructive adenotonsillar hypertrophy, and this alteration improves after tonsillectomy.

Taurine Prevents Ibuprofen-Induced Gastric Mucosal Lesions and Influences Endogenous Antioxidant Status of Stomach in Rats

Recently, free radical—induced tissue damage is implicated in the nonsteroidal anti-inflammatory drugs (NSAIDs)—involved gastric mucosal lesion. Administration of taurine, an endogenous antioxidant, is reported to be beneficial in various clinical conditions. Therefore, we decided to study the protective effect of taurine in ibuprofen-induced gastropathy and the effects of administration of taurine on the endogenous antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and reduced glutathione (GSH) of stomach. In rats, administration of taurine orally for three consecutive days (250 mg/kg body weight) protected the gastric mucosa from ibuprofen-induced, acute gastric mucosal lesion. In ibuprofen-treated rats, the lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS), a marker for free radical—induced tissue damage, is also significantly decreased by taurine. Ibuprofen treatment resulted in a significant increase in the activities of total SOD, manganese SOD (Mn-SOD), and GPX and reduced GSH. Taurine administration in ibuprofen-treated rats also showed a significant increase in the activities of the antioxidant enzymes namely total SOD, Mn-SOD, GPX, CAT, and the level of reduced GSH. The activity of copper-zinc SOD enzyme (Cu-Zn SOD) is not affected by ibuprofen or taurine. There is no temporal relation between the antioxidant status of the stomach and the tissue damage following oral administration of ibuprofen or taurine.

Comparison of relative antioxidant activities of British medicinal plant species in vitro

We have determined the relative levels of endogenous antioxidant activity in a range of British medicinal plant species (representative of a variety of plant families, selected on the basis of their widespread use in traditional herbal medicine), via competitive scavenging of the ABTS + or O 2 − radicals in vitro. A number of plant species with appreciable levels (i.e. greater than or comparable with the activity in corresponding extracts of Ginkgo biloba or Panax ginseng, as recognised phytological sources of antioxidant activity) of antioxidant activity against the ABTS + radical were identified as potentially novel sources of free radical scavenging compounds; however none of these extracts showed measurable antioxidant activity when assayed against the O 2 − radical. It, therefore, follows that any comparative determination of antioxidant activity should clearly define the radical species and assay method employed. For those extracts showing activity against the ABTS + radical, in general, it was not possible to predict the potential antioxidant capacity of a given plant species (or the most active part of the plant) on a taxonomical basis, or from its use in traditional or modern medicine. In the longer term further characterisation of the active compounds from plant species with appreciable antioxidant activity identified in the present investigation may prove of value for treatment of disorders such as Alzheimer's disease, in which free radical induced tissue damage has been implicated.

Reactive oxygen species and antioxidants in inflammatory diseases.

This paper aims to review the rôle of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits.

Iron chelation therapy.

Iron chelation therapy is essential to prevent death from cardiac toxicity in patients with thalassemia major or other severe refractory anemias who need regular blood transfusions. Iron chelating drugs also have potential for clinical use as antiproliferative agents in neoplastic diseases and to reduce free radical-induced tissue damage in rheumatoid arthritis, anthracycline-induced cardiotoxicity, and reperfusion injury. Experimental data and clinical trials also suggest they may have therapeutic value as adjuncts to antimalarial and anti-Pneumocystis carinii therapy and to reduce aluminum toxicity. There is therefore an urgent need for an orally active, inexpensive iron chelating drug, because desferrioxamine, the only currently widely available iron chelator, must be given parenterally and is expensive, making it unavailable for long-term use in many parts of the world. L1 (also known as deferiprone, 1-2 dimethyl-3-hydroxpyrid-4-one, DMHP, and CP20) has emerged as an orally active iron chelator with comparable efficiency to desferrioxamine in both short- and long-term clinical studies. Adverse side-effects, principally agranulocytosis and arthropathy, have raised doubts about its safety, and further trials are now planned to evaluate the incidence of these and other toxicities. Despite numerous studies, no other orally active agent has been shown in clinical trials to be as effective or as safe as L1.

Exercise as prevention: Do the health benefits derive in part from lower iron levels?

The mechanism by which exercise, a key component of modern preventative medicine, protects man from strikingly different diseases such as heart disease and cancer, is largely a mystery. It is proposed that exercise-induced reductions in iron levels, either through iron loss or enhanced iron storage, could be responsible for some of the beneficial effects. Possible roles for iron in coronary artery disease and cancer have recently emerged, particularly as a catalyst for oxygen free radical-induced tissue damage. The iron hypothesis is consistent with the graded reductions in mortality observed as a function of fitness level, and it is the first unified mechanism which can explain the reductions in both heart disease and cancer. If confirmed, preventative medicine in the furture will need to include close monitoring of iron levels and, possibly, occasional blood donation for those with moderately high iron stores.

The role of metal ions in ischemia/reperfusion injury in skin flaps

The role of hydroxyl radical generation by the metal-catalyzed Haber-Weiss reaction in producing injury to postischemic skin flaps in rats was evaluated. The venous drainage from groin island flaps was occluded for 7 hr and then reperfused. The flaps were infused with either deferoxamine, CaNa 2EDTA, histidine, salicylate, or vehicle (saline) at the time of reperfusion. In another experimental group, the role of hydrogen peroxide was evaluated by the infusion of catalase at the time of reperfusion. Treatment with a single dose of deferoxamine (40 mg/kg), CaNa 2EDTA (50 mg/kg), or histidine (50 mg/ kg), significantly increased the flap survival rate from 24 to 63, 75, and 63%, respectively. A large dose of salicylate (80 mg/kg) improved the flap survival rate (to 63%): a smaller dose (40 mg/kg) offered no improvement. A large dose of catalase ameliorated the survival rate (to 88%). The results suggest that the presence of metal ions is required for the expression of free radical-induced tissue damage. Hydrogen peroxide appears to be essential for the production of this injury.