Decline Of Antioxidant Status Research Articles

Therapeutic Efficacy of <i>Bacopa monnieri</i> against Aflatoxin B<Sub>1</sub> Induced Toxicity in Rats

Aflatoxin B1 (AFB1), the most frequently discovered aflatoxin in tainted foods and feed, is considered the most important risk factor. Brahmi (Bacopa monnieri) is a well-known perennial, creeping herb in the Indian Ayurvedic system. Thus, the present study was designed to evaluate the protective efficacy of Brahmi against liver damage induced by Aflatoxin B1. The whole study was conducted in two experiments. The first experiment used phytochemical estimation of BM (Bacopa monnieri). In the second experiment, animals were randomly divided into six groups with six animals in each group. Group 1 served as the control. Group 2 served as per se and received the highest dose of therapy which was 40 mg/kg for 13 days, post orally. Group 3 received AFB1 (200 μg/kg/day) for 13 days, orally Groups 4 to 6 received different doses of Brahmi (20, 30, 40 mg/kg/day PO) for 3 consecutive days after 10 days of exposure to AFB1. All animals were sacrificed after 24 hr of the last treatment. DPPH free radical scavenging activity of the plant was reported in terms of IC50 (45.30 ± 2.52 μg/ml). The presence of flavonoids and protein in the plant was reported in 29.63 ± 1.63 μg Rutin /mg, and 59.72 ± 3.30 μg BSA / mg. Acute studies showed increased lipid peroxidation and a decline in antioxidant status. Alterations in the Liver Function Test (LFT) were also observed. Oral treatment with 20-40 mg/kg Brahmi showed remarkable protection against the toxic effects of Aflatoxin B1. Biochemical results of this study demonstrate that Bacopa monnieri extract possesses protective potential against AFB1-induced hepatotoxicity due to the presence of several bioactive phytochemicals. From this study, we can conclude that treating Bacopa monnieri can protect against AFB1 challenge rats.

Quercetin mediated attenuation of cadmium-induced oxidative toxicity and apoptosis of spermatogenic cells in caprine testes in vitro.

Cadmium (Cd), an environmental toxic heavy metal, has been reported to cause testicular toxicity, which contributes to the recent decline in male fertility worldwide. Quercetin (Qcn), a major dietary antioxidant, has been shown to have protective effects under various pathological conditions. However, whether Qcn provides protection against Cd-stimulated testicular toxicity remains obscured. The present study was therefore aimed at investigating the ameliorative effect of Qcn supplementation on Cd-induced toxicity in the goat testis in vitro in a dose-(10, 50, and 100 μM) and time-dependent (4 and 8h) manner. Different cytotoxicity, genotoxicity, and biochemical analyses have been carried out using appropriate methods. Cytotoxicity in testicular cells induced by Cd treatment was apparently mitigated by Qcn treatment, evidenced by decreased apoptotic attributes or frequency in Qcn plus Cd-treated groups compared to the only Cd-treated groups. Qcn treatment provides substantial protection to the Cd-triggered aggression in oxidative (increased MDA levels) and total antioxidant capacity (reduced FRAP activity) in testicular tissue, indicating the anti-oxidative function of Qcn against Cd exposure. Moreover, Cd-induced decline in antioxidant status (CAT, SOD, and GST activity) was markedly restored by Qcn supplementation in testicular tissue. In conclusion, this study shows that Qcn treatment significantly attenuated the Cd-evoked testicular damage, suggesting its beneficial potential in preventing or at least in managing the gonadotoxicity in males induced by steadily increasing Cd contamination in the environment.

Cynodon dactylon alleviates radiation-induced behavioral and biochemical changes in the cerebral cortex of mice

Cynodon dactylon is herb with its rich antioxidant phytoconstituents it has been widely used in traditional medicine. The present study was aimed to investigate the ameliorative role of hydro alcoholic extract of Cynodon dactylon on cerebral cortex in the mice exposed to lethal dose of radiation. Swiss albino mice were treated with 0.25 and 1 g/kg body weight of Cynodon dactylon extract (CDE) via oral gavage for 7 days and subjected to 5 Gy of gamma radiation. All mice were subjected to behavioral and cognitive functions tests. Further, potent markers of radiation including biochemical parameters were evaluated in the cerebral cortex. Mice irradiated with γ- rays displayed a significant decline in the behavior and cognitive functions. Further, decline in antioxidant status and increase in the oxidative stress markers was observed. Pretreatment of hydroalcoholic extract of Cynodon dactylon before exposure to γ-radiation showed significant improvement in the cognitive and behavioral analysis. Further, increase in antioxidant status and a decline in level of oxidative stress markers was observed. The present study confirms the potent protective role of Cynodon dactylon on radiation induced oxidative damage to the cerebral cortex.

Flavonoid-rich fraction of Lasianthera africana leaves alleviates hepatotoxicity induced by carbon tetrachloride in Wistar rats

Lasianthera africana P. Beauv. (Icacinaceae) is a good source of natural antioxidants, having the potential to protect against oxidative stress-related diseases and complications. This study investigated the antioxidant, hepatoprotective and curative effects of flavonoid-rich fraction of L. africana leaves (LAFRF) against carbon tetrachloride-induced hepatotoxicity in Wistar rats. Phytochemical, nutrient content, and in vitro antioxidant activity of LAFRF were determined by standard methods. Fifty Wistar rats were randomized into 10 groups (n = 5). Groups 1 and 2 served as normal and CCl4 controls, respectively. Groups 3A–6A constituted the protective study while groups 3B–6B represented the curative study. The effects of LAFRF at 3, 10, and 30 mg/kg body weight (b.w.) on lipid peroxidation, antioxidant status, liver enzymes activities, and histology of CCl4-intoxicated rats were assessed. LAFRF total flavonoids (281.05 ± 7.44 mg QE/g), indicated LD50 above 5000 mg/kg b.w., and scavenged ABTS*+ with an IC50 of 5.05 ± 0.00 µg/mL relative to butylated hydroxytoluene (4.16 ± 0.00 µg/mL), and a concentration-dependent increase in total antioxidant capacity. Carbon tetrachloride (1 mL/kg) triggered significant (p < 0.05) increases in malonedialdehyde concentration (2.67 ± 0.21 mg/mL), with a corresponding decline in antioxidant status, and increases in alkaline phosphatase, alanine and aspartate aminotransferase activities (68.00 ± 9.59 IU/L, 79.60 ± 5.03 IU/L and 81.80 ± 3.96 IU/L), respectively. LAFRF significantly (p < 0.05) lowered lipid peroxidation levels, liver enzyme activities, increased antioxidant status, and improved hepatic histo-architecture of pre- and post LAFRF-treated rats. This demonstrates its high antioxidative, hepatoprotective and curative effects, indicating its potential for future drug development.

Ipriflavone and Ipriflavone loaded albumin nanoparticles reverse lipopolysaccharide induced neuroinflammation in rats.

Neuroinflammation causes neurodegenerative conditions like Alzheimer's disease (AD). Ipriflavone (IP), therapeutic compound to postmenopausal osteoporosis, has limited estrogenic activity and is accounted as AChE inhibitor. The developing of drug delivery systems to enable drug targeting to specific sites increases the drug therapeutic effect. The aim of the present study was to formulate and evaluate ipriflavone loaded albumin nanoparticles (IP-Np) along with free ipriflavone against lipopolysaccharide (LPS) induced neuroinflammation in rats. Neuroinflammation was induced by intra-peritoneal (i.p) injection of LPS (250 μg/kg rat body weight) then treatments were conducted with (1) ipriflavone at two doses 50 mg/kg and 5 mg/kg, (2) IP-Np (5 mg ipriflavone/kg) or (3) IP-Np coated with polysorbate 80 (IP-Np-T80) (5 mg ipriflavone/kg). The alteration of the inflammatory response in male adult Wistar rats' brain hippocampus was investigated by examining associated indices using biochemical and molecular analyses. A significant upsurge in inflammatory mediators and decline in antioxidant status were observed in LPS-induced rats. In one hand, ipriflavone (50 mg/kg), IP-Np and IP-Np-T80 ameliorated LPS induced brain hippocampal inflammation where they depreciated the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and enhanced antioxidant status. In another hand, ipriflavone at dose (5 mg/kg) didn't show the same therapeutic effect. The current study provides evidence for the potential neuroprotective effect of ipriflavone (50 mg/kg) against LPS-induced neuroinflammation in rats through its anti-inflammatory and antioxidant activities. Moreover, nanoparticles significantly attenuated neuroinflammation in concentration lower than the effective therapeutic dose of free drug ten times.

Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis

The rapid emergence of various pesticides in the market is inevitable due to the demands from agriculture industries and domestic needs to control nuisance pests and to sustain green resources worldwide. However, long-term exposure to pesticide has led to adverse effects on male fertility. Organophosphate diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothiote) is an often abusively used pesticide, as it is effective and economical. This study is to determine the adverse effects of low-dose diazinon exposure on the male reproductive system. In this study, 72 Sprague–Dawley rats were segregated into 1, 2, and 8 weeks of exposure groups and further sub-grouped (n = 6) to receive 0, 10, 15, and 30 mg/kg body weight diazinon treatment. Rats were gavaged orally with diazinon and sacrificed under anaesthesia the day after the last exposure. Our results showed that consistent diazinon exposure decreased glutathione and catalase, and increased lipid peroxidation which together lead to diazinon-mediated oxidative stress. Additionally, diazinon increased serum lactate dehydrogenase and decreased serum testosterone, which may have caused sperm and histopathological anomalies. In conclusion, exposure to diazinon caused changes in lipid peroxidation and sperm, and these two effects might be causally linked.

Medicinal Herbs can Play Significant Role in Attenuation of Ischemia and Reperfusion Injury

Nature has been a source of medicinal treatments for thousands of years and plant-derived products continue to play an essential role in the primary health care of about 80-85% of the world’s population. Medicinal herbs are widely used in Ayurveda, the Indian System of Medicine and have been observed to possess numerous activities with regard to cardiovascular system viz. antiplatelet, hypolipidemic, anti-inflammatory, hypoglycemic and hypotensive actions. Hence, these herbal extracts traditionally used have been evaluated scientifically in the present study with an aim to define the role of these agents in limiting the deleterious effects of myocardial ischemia and reperfusion (IR) injury by providing scientific data to validate their use as prophylactic approaches or as an adjunct to standard treatment (synthetic compounds employed in conventional treatment protocols) of ischemic heart disease. The efficacy of Withania somnifera (Ws), Curcuma longa (Cl) and Ocimum sanctum (Os), and herbal combination (HCB) including {Ws (50 mg/kg) + Cl (100 mg/kg) + Os (75 mg/kg} to limit injury in the setting of myocardial ischemia and reperfusion was explored in the present study. An open chest left anterior descending coronary artery (LAD) occlusion and reperfusion induced myocardial injury was used as the experimental model. Wistar albino rats were divided into ten groups and orally fed saline once daily (sham, control IR) or medicinal herbs (Ws/Cl/Os/HCB; Ws-IR, Cl-IR/Os-IR/HCB-IR) respectively for 1 month. On the 31st day in the rats of the Control IR and Ws-IR, Cl-IR/Os-IR/HCB-IR groups, LAD was occluded for 45 min, and reperfused for 1 h. Hemodynamic parameters were recorded at preset points and subsequently sacrificed for biochemical, immunohistochemical and pathological studies. In the control IR group, significant ventricular dysfunction, cardiac necrosis, apoptosis; decline in antioxidant status and elevation in lipid peroxidation was observed. Chronic oral treatment with HCB per se for 1 month resulted in significant enhancement of the myocardial endogenous antioxidant enzymes. Pretreatment with Ws, Cl and the herbal combination exerted significant cardioprotective effects in the experimental model of myocardial injury. The most remarkable observation of the present study was that cardioprotective effect exerted by HCB treatment was found to be superior to that shown by singular treatment with individual herbal extracts. The combination of herbal extracts was found to significantly ameliorate the ischemia and reperfusion cardiomyocyte apoptosis, cardiac dysfunction, compromised antioxidant status and histopathologic alterations as compared to control IR group. Cardioprotection by HCB treatment may be attributed to its favorable hemodynamic effects, myocardial adaptogenic properties, and significant antioxidant and antiapoptotic properties. Furthermore, HCB decreased the severity of pathological changes and significantly preserved the myocardial creatinine phosphokinase confirming its myocardial salvaging effects. Results clearly demonstrated the therapeutic potential of the herbal drugs in the treatment of myocardial ischemia and reperfusion injury. If the beneficial effects can be established in-patients, these findings may represent a novel adjunctive therapy of ischemic heart disease and Myocardial Infarction.

Bacopa monniera protects rat heart against ischaemia–reperfusion injury: role of key apoptotic regulatory proteins and enzymes

Rat isolated hearts were perfused in a Langendorff model to study the cardioprotective effects of Bacopa monniera, a medicinal herb used in the Indian system of medicine, on cardiomyocyte apoptosis and antioxidant status following ischaemia-reperfusion (I-R) injury. Forty-eight rats were randomly divided into four groups (12 in each group): sham group (no ischaemia-reperfusion injury), B. monniera control group (orally fed B. monniera at a dose of 75 mg/kg, for three weeks); ischaemia-reperfusion control group(subjected to ischaemia-reperfusion-induced myocardial injury) and B. monniera-treated group (same protocol as ischaemia-reperfusion control group except that rats also fed B. monniera). Post-ischaemic reperfusion injury resulted in significant cardiac necrosis, apoptosis, depression of heart rate, decline in antioxidant status and elevation in lipid peroxidation. Oral administration of B. monniera per se for three weeks to healthy rats caused augmentation of myocardial antioxidants, superoxide dismutase, catalase and glutathione, along with induction of heat shock protein 72 (HSP72). Ischaemia-reperfusion-induced biochemical and histopathological perturbations were significantly prevented by B. monniera (75 mg/kg) pre-treatment. Interestingly, B. monniera also restored the antioxidant network of the myocardium and reduced myocardial apoptosis, caspase 3 and Bax protein expression. Histopathological studies and myocardial creatine phosphokinase content further confirmed the cardioprotective effects of B. monniera (75 mg/kg) in the experimental model of ischaemia-reperfusion injury. The study provides scientific basis for the putative therapeutic effect of B. monniera in ischaemic heart disease.

Antioxidant status of elite athletes remains impaired 2 weeks after a simulated altitude training camp

It has been shown that the antioxidant status was altered by the "live high-train low" (LHTL) method, however, no information is available regarding the antioxidant restoration during the recovery period. We tested the hypothesis that the antioxidant status is impaired by 18 days LHTL in elite athletes and remained altered after 14 days of recovery. Eleven elite cross-country skiers from the French Skiing Federation were submitted to 18-day endurance training. Six (hypoxic group; HG) trained at 1,200 m and lived in hypoxia (simulated altitude of 2,500 m-3,000 m-3,500 m) and 5 (control group; CG) trained and lived at 1,200 m. Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric reducing antioxidant power (FRAP), trolox equivalent antioxidant capacity (TEAC) lipid-soluble antioxidants (alpha-tocopherol, beta-carotene and lycopene) were measured at rest, before (PRE), the first day after (POST1) and again 2 weeks (POST14) after the training. Intakes of vitamins A and E were evaluated from the dietary recording. In POST1, FRAP and TEAC decreased in both groups, however, the TEAC decrease persisted in POST14 for HG only. Lycopene and beta-carotene decreased in POST1 for HG and remained lower in POST14. Finally, AOPP increased only for HG in POST1. The general decline of antioxidant status for both groups might result from insufficient intakes in vitamins A and E. This is the first study to show that the antioxidant status did not return to baseline 2 weeks after 18 days of LHTL training.

Withania somnifera provides cardioprotection and attenuates ischemia–reperfusion induced apoptosis

The present study was undertaken to evaluate the cardioprotective mechanisms of Withania somnifera (Ws), in the setting of ischemia and reperfusion (IR) injury. Wistar rats were divided into three groups and received orally saline (sham, control IR) and Ws-50 mg/kg (Ws-IR), respectively, for 1 month. On the 31st day, in the rats of control IR and Ws-IR group, LAD coronary artery occlusion was undertaken for 45 min followed by 1 h reperfusion. Subsequently, all the animals were sacrificed for biochemical, immunohistochemical {Bax and Bcl-2 protein}, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) positivity and histopathological studies. Post-ischemic reperfusion injury resulted in significant cardiac necrosis, apoptosis, decline in antioxidant status and elevation in lipid peroxidation in the IR control group as compared to sham. Ws prior-treatment favorably restored the myocardial oxidant-antioxidant balance, exerted marked anti-apoptotic effects {upregulated Bcl-2 (p<0.001) protein, decreased Bax (p<0.01) protein, and attenuated TUNEL positivity (p<0.01)}, and reduced myocardial damage as evidenced by histopathologic evaluation. The antioxidant and anti-apoptotic properties of Ws may contribute to the cardioprotective effects.

Relationship between antioxidant potential and oxidative damage to lipids, proteins and DNA in aged rats

Oxidative stress has been implicated to play a major role in aging and age-related diseases. In the present study, we investigated the effects of aging on the total antioxidant capacity, uric acid, lipid peroxidation, total sulfhydryl group content and damage to DNA in adult (6 months), old (15 months) and senescent (26 months) male Wistar rats. The antioxidant capacity, determined by phycoerythrin-based TRAP method (total peroxyl radical-trapping potential) was significantly decreased in the plasma and myocardium of old and senescent rats, whereas plasma level of uric acid was elevated in 26-month-old rats. Age-related decline in plasma and heart antioxidant capacity was accompanied by a significant loss in total sulfhydryl group content, increased lipid peroxidation and higher DNA damage in lymphocytes. Correlations between TRAP and oxidative damage to lipids, proteins and DNA suggest that the decline in antioxidant status may play an important role in age-related accumulation of cell damage caused by reactive oxygen species.

Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury

The efficacy of lycopene to limit myocardial injury after ischemia and reperfusion was explored in the present study. Adult male albino Wistar rats were divided into three experimental groups and orally received olive oil as vehicle (sham and control I-R) or lycopene 1 mg/kg dissolved in olive oil (lycopene treated group) respectively for 31 days. On the 31st day, animals of the control I-R and lycopene treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. The ischemia-reperfusion injury resulted in significant cardiac necrosis, depression in hemodynamics, decline in antioxidant status and rise in lipid peroxidation product levels in the control I-R group as compared to sham control. In histopathological examinations myocardial damage produced after I-R was significantly prevented in the lycopene treated group. Lycopene treatment resulted in preservation of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I-R group. Furthermore, I-R-induced lipid peroxidation was significantly inhibited in the lycopene treated group. These beneficial cardioprotective effects also translated into the functional recovery of the heart. The beneficial effect of lycopene likely results from the suppression of oxidative stress, which results in the reduction of myocardial injury.

Protective effects of Curcuma longa on ischemia-reperfusion induced myocardial injuries and their mechanisms

The present study was undertaken to evaluate the cardioprotective potential of Curcuma longa (Turmeric) in the ischemia-reperfusion (I/R) model of myocardial infarction (MI). Wistar rats were divided into three groups and received saline orally (sham, control I/R group) and Curcuma longa 100 mg/kg (CL-100 treated group) respectively for one month. On the 31st day, rats of the control I/R and Cl treated groups were subjected to 45 min of occlusion of the LAD coronary artery and were thereafter reperfused for 1 h. I/R resulted in significant cardiac necrosis, depression in left ventricular function, decline in antioxidant status and elevation in lipid perodixation in the control I/R group as compared to sham control. Myocardial infarction produced after I/R was significantly reduced in the Cl treated group. Cl treatment resulted in restoration of the myocardial antioxidant status and altered hemodynamic parameters as compared to control I/R. Furthermore, I/R-induced lipid peroxidation was significantly inhibited by Cl treatment. The beneficial cardioprotective effects also translated into the functional recovery of the heart. Cardioprotective effect of Cl likely results from the suppression of oxidative stress and correlates with the improved ventricular function. Histopathological examination further confirmed the protective effects of Cl on the heart.