Free Radical Scavenging Enzymes Research Articles

Free radical scavenging enzymes from two Fabaceae plants

Free radical scavenging enzymes from two Fabaceae plants

ALLEVIATION OF CHILLING INJURY IN TROPICAL AND SUBTROPICAL FRUITS

Chilling injury in tropical and subtropical fruits can be alleviated by low temperature preconditioning, intermittent warming, heat treatment, controlled atmosphere storage, treatments with calcium or other chemicals, waxing, film packaging, genetic modification, or applications with ethylene, abscisic acid, polyamines, methyl jasmonate, methyl salicylate, or other natural compounds. The effectiveness of each treatment varies with the commodity, the maturity of the fruit, and the dosage of the treatment. Low temperature conditioning and intermittent warming maintain high levels of phospholipids, increase the degree of unsaturation of fatty acids, increase the levels of spermidine and spermine, and stimulate the activities of free radical scavenging enzymes. Heat treatment induces heat shock proteins (HSP), suppresses oxidative activity, and maintains membrane stability. Methyl jasmonate and methyl salicylate stimulates the synthesis of some stress proteins, such as HSP, pathogenesis-related (PR)-proteins, and alternative oxidase (AOX) and can activate lipoxygenase gene expression and induce synthesis of abscisic acid and polyamines. Polyamines may act as free radical scavengers and membrane stabilizers. All of these processes can enhance chilling tolerance of tissues and alleviate chilling injury of tropical and subtropical fruits.

Antioxidative status and lipid peroxidation in kidney tissue of rats fed with vitamin B6-deficient diet

Introduction: The aim of this study was to evaluate lipid peroxidation (LP) and free radical scavenging enzyme activities in kidney tissue of vitamin B6-deficient rats. Material and Methods: The rats were divided into control and vitamin B6-deficient groups. After 4 weeks of feeding, animals in all groups were anesthetized by thiopental sodium (50 mg/kg). Thoraces were opened, 2 mL blood samples were taken from aortas, then the rats were killed by cervical dislocation, and kidney tissues were removed. Biochemical measurements in kidney tissue were carried out using a spectrophotometer. Results: Total superoxide scavenger activity (TSSA), nonenzymatic superoxide scavenger activity (NSSA), superoxide dismutase (SOD) activities, and antioxidant potential (AOP) values in the vitamin B6-deficient group were significantly lower than those of the control group, whereas glutathione peroxidase (GSH-Px), glutathione reductase (GRD), glutathione-S-transferase (GST) activities, and malondialdehyde (MDA) level were significantly higher than those of the control group (p < 0.05). Discussion: The results show that vitamin B6 deficiency causes an attenuation in antioxidant defense system and an increase in oxidative stress in kidney tissue of rats.

Role of oxidative stress in animal model of visceral pain

Reactive oxygen species play an important role both in physiological and pathophysiological reactions. The aim of this study was to determine the role of free radicals and antioxidants in the development of visceral pain. Visceral pain was produced by colorectal distension (CRD) in adult rats. CRD was caused by insertion of a lubricated latex balloon into the descending colon and rectum followed by inflation to 80 mm Hg for 10 min. During CRD, visceral pain was rated on 0–3.5 point scale. Oxidative stress was determined indirectly by measurement of free radical scavenging enzymes (glutathione peroxidase (GPx) and superoxide dismutase (SOD)) in the blood, liver and brain. Following CRD we observed (1) all rats expressed signs of visceral pain (overall rating was 1.83), (2) SOD and GPx levels were increased in the liver and blood, and decreased in the brain samples and (3) administration of the antioxidant Trolox, a water-soluble derivate of vitamin E, prior to CRD, prevented SOD and GPx changes in the liver, blood and brain, but did not affect pain scores. It was concluded, that CRD as a model of visceral pain, increases oxidative stress in animals, which could be prevented by prior administration of antioxidants; however, antioxidants did not attenuate signs of visceral pain caused by CRD.

LIBS-Based Detection of Antioxidant Elements in Seeds of Emblica officinalis

The aim of the study was to determine the effect of the elements of the extract of seed from Emblica officinalis on antioxidant enzymes and osmotic fragility of erythrocytes membrane in normal as well as streptozotocin-induced severely diabetic albino Wister rats. The results revealed that the untreated diabetic rats exhibited increase in oxidative stress as indicated by significantly diminished activities of free radical scavenging enzymes such as catalase (CAT) and superoxide dismutase (SOD) by 37.5% (p < 0.001) and 18.6% (p < 0.01), respectively. However, the E. officinalis seed extract treatment showed marked improvements in CAT and SOD activities by 47.09% (p < 0.001) and 21.61% (p < 0.001), respectively. The enhanced lipid peroxidation by 30.87% (p < 0.001) in erythrocytes of untreated diabetic rats was significantly accentuated in the extract treated animals by 23.72% (p < 0.001). The erythrocytes showed increased osmotic fragility due to diabetes in terms of hemolysis. It attained the normal level in diabetic treated group. The findings thus suggest that E. officinalis seed extract has the potential to be exploited as an agent to boost the antioxidant system in the diabetic animal model. Laser-induced breakdown spectroscopy has been used as an analytical tool to detect major and minor elements like Mg, Fe, Na, K, Zn, Ca, H, O, C, and N present in the extract. The higher concentration of Ca (II), Mg (II) and Fe (II) as reflected by their intensities are responsible for the antioxidant potential of E. officinalis.

Age-related protective effect of deprenyl on changes in the levels of diagnostic marker enzymes and antioxidant defense enzymes activities in cerebellar tissue in Wistar rats

Antioxidants are free radical scavengers and protect living organisms against oxidative damage to tissues. Experimental evidence implicates oxygen-derived free radicals as important causative agents of aging and the present study was designed to evaluate the age-related effects of deprenyl on the antioxidant defense in the cerebellum of male Wistar rats. Experimental rats of three age groups (6, 12, and 18 months old) were administered with liquid deprenyl (2 mg/kg body weight/day for a period of 15 days i.p) and levels of diagnostic marker enzymes (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase) in plasma, lipid peroxides, reduced glutathione and activities of glutathione-dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (catalase and superoxide dismutase) in the cerebellar tissue were determined. Intraperitonial administration of deprenyl (2 mg/kg body weight/day for a period of 15 days) significantly (p < 0.05) attenuated the age-related alterations noted in the levels of diagnostic marker enzymes plasma of experimental animals. Deprenyl also exerted an antioxidant effect against aging process by hindering lipid peroxidation to an extent. Moderate rise in the levels of reduced glutathione and activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes was also observed. The results of the present investigation indicated that the protective potential of deprenyl was probably due to the increase of the activity of the free radical scavenging enzymes or to a counteraction of free radicals by its antioxidant nature or to a strengthening of neuronal membrane by its membrane-stabilizing action. Histopathological observations also confirmed the protective effect of deprenyl against the age-related aberrations in rat cerebellum. These data on the effect of deprenyl on parameters of normal aging provides new additional information concerning the anti-aging potential of deprenyl.

The role of erythropoietin in the protection of gastric mucosa from indometacin-induced gastric injury and its relationship with oxidant and antioxidant parameters in rats

Erythropoietin has anti-oxidative and anti-inflammatory activity. We wanted to evaluate its activity in preventing damage to the gastric mucosa. We examined the protective effect of erythropoietin on indometacin-induced gastric mucosa damage in the rat stomach and compared its potency with that of famotidine. We also measured effects on oxidant and antioxidant parameters in the rat stomach. Famotidine and erythropoietin 2500 and 5000 IU/kg reduced the ulcer area by 98%, 31% and 58%, respectively, compared with the indometacin group. Superoxide dismutase activity and glutathione level were decreased and myeloperoxidase activity increased in the indometacin group compared with healthy rats. Famotidine and erythropoietin at all doses increased superoxide dismutase and glutathione levels significantly compared with the indometacin group. Myeloperoxidase activity was decreased by erythropoietin and famotidine. These results support the view that erythropoietin counteracts the effects of indometacin in inducing gastric ulcer and could be used as a an antiulcer compound. Its antiulcer effect is less potent than that of famotidine. The antiulcerogenic effects of erythropoietin may be related to its intrinsic ability to sustain the activities of free-radical scavenging enzymes and the bioavailability of glutathione.

Effect of chrysin on hepatoprotective and antioxidant status in d-galactosamine-induced hepatitis in rats

Chrysin is a natural, biologically active compound present in many plants and possesses potent anti-inflammatory, anticancer and antioxidation properties. This work was designed to investigate the effect of chrysin, on the hepatoprotective efficacy in d-galactosamine-intoxication rats. d-galactosamine-induced toxicity was manifested by the elevation of serum hepatic marker enzyme activities (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and the lipid peroxidation process and by decreasing the antioxidant capacity of the plasma, erythrocyte and tissues. Treatment with chrysin (25, 50 and 100 mg/kg body weight) decreased hepatic marker enzyme activities and lipid peroxidation products such as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, increased the activities of free-radical scavenging enzymes superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants reduced glutathione, vitamin C and vitamin E. These findings demonstrate that chrysin acts as a hepatoprotective and antioxidant agent against d-galactosamine-induced hepatotoxicity.

Effects of a Flavonoid Extract from Cynomorium songaricum on the Swimming Endurance of Rats

The present study investigated the effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats by measuring changes of free radical scavenging enzymes, such as CuZn-SOD (copper, zinc-superoxide dismutase) and GSH-px (glutathione peroxidase), and body weights. Significant and dose-dependent antioxidant and anti-fatigue effects of flavonoids (rutin, catechin and isoquercitrin) on swimming rats were observed during 10 days of swimming exercise. After treatment with the flavonoid extract at doses of 0.5, 1.0, and 2.0 g/kg body weight, the CuZn-SOD and GSH-px activities in swimming rats were increased by 1.4%, 3.3%, 4.1% and 112.2%, 208.7%, 261.7%, respectively, while the levels of MDA (malondialdehyde) were decreased by 64.7%, 79.4%, and 86.4% respectively. Furthermore, the average body weight and the total swimming time were increased by 3.1%, 8.8%, 10.6%, and 7.7%, 34.5%, 61.5%, respectively. Our experimental results suggest that flavonoid supplementation could not only reduce free radical formation and scavenge free radicals, but also enhance endurance exercise performance by reducing muscle fatigue.

Protective effect of vitamin C against chlorpyrifos oxidative stress in male mice

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of chlorpyrifos toward male mice and the oxidative stress of the sub-lethal dose (1/10 LD 50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) activities. Also, the protective effects of vitamin C (200 mg/kg body weight, bw) 30 min before or after administration of chlorpyrifos were investigated. The results demonstrated that the LD 50 value of chlorpyrifos was 134.95 mg/kg bw. The oral administration of 13.495 mg/kg chlorpyrifos significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD and GST. However, GPx activity remained unchanged, while the level of GSH and G6PD activity were decreased. Vitamin C treatment to chlorpyrifos intoxicated mice decreased LPO level and GST activity, normalized CAT, SOD and G6PD activities, while GSH content was increased. We conclude that vitamin C significantly reduces chlorpyrifos-induced oxidative stress in mice liver and the protective effect of the pre-treatment with vitamin C is better than the post-treatment.

Cochlodinium polykrikoides blooms and clonal isolates from the northwest Atlantic coast cause rapid mortality in larvae of multiple bivalve species

Globally, many commercial bivalve populations have declined in recent decades. In addition to overharvesting and habitat loss, the increasing frequency and intensity of harmful algal blooms (HABs) are likely to contribute to bivalve losses, particularly in cases where blooms negatively impact larval stages. This paper reports on the lethal effects of clonal cultures and blooms of Cochlodinium polykrikoides from the US Atlantic coast on the larvae of three species of commercially and ecologically valuable bivalves: the Eastern oyster (Crassostrea virginica), the bay scallop (Argopecten irradians), and the Northern quahog (hard clam; Mercenaria mercenaria). Both cultures and blooms of C. polykrikoides were highly toxic to all three species of bivalve larvae causing 80–100% mortality during 24- to 72-h exposures at concentrations of 1–2 × 103 cells ml−1. Toxicity was dependent on cell densities, growth stage of C. polykrikoides (i.e. cultures in exponential stage growth were more toxic than later stages), exposure time of larvae to cells (i.e. longer exposure caused higher mortality), the age of larvae (i.e. younger larvae were more sensitive), and the relative abundance of C. polykrikoides (i.e. the presence of other microalgae decreased toxicity). Free radical-scavenging enzymes (peroxidase and catalase) and the removal of C. polykrikoides cells (i.e. culture filtrate) significantly increased larval survival suggesting toxicity is maximized by contact with live cells and may involve labile toxins bound by these compounds including e.g. reactive oxygen species. The toxicity of C. polykrikoides to bivalve larvae was generally more severe than other HAB species (e.g. Karenia brevis, Karlodinium veneficum, Alexandrium tamarense, Prorocentrum minimum). Since the bivalves in this study spawn in the months when C. polykrikoides blooms on the east coast of North America, these results suggest that these blooms may have detrimental effects on efforts to restore these already diminished populations.

Polyketal microparticles for therapeutic delivery to the lung

Inflammation in the setting of interstitial lung disease (ILD) occurs in the distal alveolar spaces of the lung, which presents significant challenges for therapeutic delivery. The development of aerosolizable microparticles from non-immunogenic polymers is needed to enable the clinical translation of numerous experimental therapeutics that require localization to the deep lung and repeated delivery for optimal efficacy. Polyketals (PK), a family of polymers, have several unique properties that make them ideal for lung delivery, specifically their hydrolysis into non-acidic, membrane-permeable compounds and their capacity to form microparticles with the aerodynamic properties needed for aerosolization. In this study, we tested the lung biocompatibility of microparticles created from a polyketal polymer, termed PK3, following intratracheal instillation in comparison to commonly used PLGA microparticles. We furthermore tested the initial efficacy of PK3 microparticles to encapsulate and effectively deliver active superoxide dismutase (SOD), a free radical scavenging enzyme, in a model of lung fibrosis. Our findings indicate that PK3 microparticles display no detectable level of alveolar or airway inflammation, whereas PLGA induced a small inflammatory response. Furthermore, SOD-loaded into PK3 microparticles maintained its activity upon release and, when delivered via PK3 microparticles, inhibited the extent of lung fibrosis.

The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD 50) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione- s-transferase (GST). Also, the protective effect of vitamin C (200 mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD 50) of imidacloprid after 24 h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment.

Effects of Malaysian Tualang honey supplementation on glycemia, free radical scavenging enzymes and markers of oxidative stress in kidneys of normal and streptozotocin-induced diabetic rats

Background and aim Hypertension and diabetes mellitus co-exist. It is reported that hypertension is at least twice as common in diabetic subjects when compared with non-diabetic population. Excess generation of free radicals causes oxidative stress which is implicated in the development of hypertension and progression of diabetes as well as its complications. This study investigated the effects of honey on hyperglycemia, antioxidant enzymes, oxidative stress markers and renal histology of normal and streptozotocin (STZ)-induced diabetic rats.

Amelioratory effect of vitamin E on organophosphorus insecticide diazinon-induced oxidative stress in mice liver

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of organophosphate insecticides (OPIs), the aim of this study was to investigate the ameliorative properties of vitamin E (vitE) against the subchronic effect of diazinon (DZN) on oxidative damage markers such as lipid peroxidation (LPO) and the antioxidant defense system (ADS) in the liver of male MFI albino mice. The groups were intraperitoneally (i.p) administered with either vehicle or vitE (100 mg/kg body weight) or ¼ LD 50 of DZN (16.25 mg/kg b.w.) or ½ LD 50 of DZN; 32.5 mg/kg b.w) or ¼ LD 50–DZN + vitE or ½ LD 50 + vitE every consecutive day for 14 days. Hepatic damage markers analysis revealed that alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly decreased in both DZN doses. Also, the significantly increased levels of biomarkers of oxidative stress as LPO and protein carbonyl (PC) and the decreased antioxidant defenses like reduced glutathione (GSH), and free radical scavenger enzymes viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GSH-Rx) were noted in DZN-treated groups as compared to control group. Distinctly lower levels of GSH and increased levels of LPO, along with alterations in endogenous antioxidant enzymes were evident in hepatic toxicity of DZN which is dose-dependent. Hepatic specific marker enzymes were restored to normalcy in mice supplemented with vitE following treatment with DZN which otherwise was decreased in the DZN-treated mice. The results show that co-treatment of vitE with DZN prevents or diminishes the oxidative stress of DZN-treated mice and may act as a putative protective agent against DZN-induced liver tissue injury.

Comparative Antioxidant Level in Renal and Liver Tissues of Mice Treated with Fixed Dose Combination of Cefepime-Amikacin Reconstituted in Solvent vs Water for Injection

In order to investigate the protective role of cefepime plus amikacin (Potentox) reconstituted with solvent for injection vs cefepime and amikacin alone as well as potentox reconstituted with water for injection, the mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 23 ± 2oC, humidity 65± 5% and with artificial fluorescent light (10-14 hrs. of light and dark, respectively). Thirty Mus musculus mice (weighing 30 ± 5 g) were divided into five groups containing six mice in each group. Group- I Control (Normal Saline), Group-II cefepime (28.5 mg/Kg body weight/day), Group-III amikacin (7.14mg/Kg body weight/day), Group-IV cefepime plus amikacin reconstituted with water for injection (35.7mg/Kg body weight/day) and Group-V cefepime plus amikacin reconstituted with solvent for injection (35.7mg/Kg body weight/day). The level of antioxidant enzymes such as superoxide dismutase and catalase along with malonaldialdehyde (free radical mediated damage) and some extracellular levels namely creatinine, uric acid, serum glutamyl oxaloacetic transaminase and serum glutamyl pyruvic transaminase were also analyzed. In cefepime, amikacin and potentox reconstituted with water for injection treated groups, antioxidant enzyme activities were significantly decreased and the level of malonaldialdehyde as well as oxidant levels were significantly higher than those in the control group. Our results indicated that the protective effect of potentox reconstituted with solvent for injection increases the activity of antioxidant enzymes with the reduction of lipid peroxidation and oxidant level. These findings suggest that fixed dose combination of cefepime plus amikacin (Potentox) reconstituted with solvent for injection was found to be more effective and improve the activities of free radical scavenging enzymes. Keywords: Fixed dose combination, cefepime, amikacin, free radical, Potentox, antioxidant enzymes, malonaldialdehyde

Run for your life: exercise, oxidative stress and the ageing endothelium.

Exercise is good for you. Elite athletes live longer than the general population (Teramoto & Bungum, 2009). Physically active middle-aged men live on average 2.3 years longer than sedentary men (Byberg et al. 2009). The mechanisms underlying the benefits of exercise on morbidity and mortality are multiple and complex (Williams et al. 2007; Heckman & McKelvie, 2008). The benefits of exercise training on blood pressure are well described and the mechanism for this may at least in part be due to improvements in endothelium-dependent vasodilatation (Heffernan et al. 2009). This is thought to result from increased shear stress in the arterial wall resulting in upregulation of genes coding for nitric oxide bioavailability (Kojda & Hambrecht, 2005). However, there are studies reporting no change in nitric oxide metabolism following exercise training in healthy humans (Green et al. 2004) and so the possibility exists that in some settings this mechanism is less important. In the elderly, forearm blood flow in response to acute exercise is impaired relative to younger subjects (Kirby et al. 2009); however, there is some evidence in older people that longer term exercise training can improve endothelium-dependent vasodilatation (Black et al. 2008). In an article in a recent issue of The Journal of Physiology, Durrant et al. (2009) elegantly demonstrated that endothelial function, as assessed by acetylcholine induced relaxation, was restored in aged mice following 10–14 weeks of voluntary exercise on a running wheel to a level similar to that observed in younger mice that also have access to a wheel. The mechanism underlying this observation is suggested to be enhanced NO availability as a result of increased NOS expression, coupled with reduction in oxidative stress. Activity of the oxidant stress generating enzyme NADPH oxidase was reduced while activity of the free radical scavenging enzyme superoxide dismutase was increased in the aorta of free running aged mice. This study therefore demonstrates that the aged mouse endothelium retains an adaptive response to exercise that can re-establish vasodilatory function to that observed in younger mice. Furthermore, the mechanism for this appears to relate to reduced oxidative stress, which in turn permits greater bioavailability of nitric oxide. While it is encouraging that endothelial function can be restored in ageing there are a number of key questions that arise from the underlying hypothesis implicit in this work and its relation to human ageing and disease.

Free radicals are present in human serum of Catha edulis Forsk (Khat) abusers

Objective Khat ( Catha edulis Forsk) is a naturally occurring drug with an amphetamine-like structure and action. It has been postulated that amphetamine induces free radical formation. On this basis, we have hypothesized that Khat may promote synthesis of reactive oxygen and nitrogen species in the same way that amphetamine promotes free radical production. Materials and methods Forty male subjects were enrolled in two groups: those with a chronic Khat chewing habit ( n = 20), and those without a chewing habit (controls; n = 20). Both groups were matched with regard to age. Total antioxidant capacity and cholinesterase (AChE) activity were assayed. Results This study showed that Khat consumption inhibited serum free radical scavenging enzymes, resulting in significant elevations in free radical loads ( p = 0.01; n = 20). We also showed that serum acetyl cholinesterase (AChE) was significantly inhibited in the Khat chewing group ( p = 0.002; n = 20). Conclusion These results show for the first time that Khat may contribute to high levels of free radicals. In addition, the presence of pesticides in Khat leaves is implicated in the inhibition of AChE activity.

Differential regulation of neuronal and inducible nitric oxide synthase (NOS) in the spinal cord of mutant SOD1 (G93A) ALS mice

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme superoxide dismutase-1 (SOD1) are a cause of familial ALS but it is not known how mutations lead to cell death. Free radicals such as nitric oxide (NO) are thought to play a key pathogenic role. NO is synthesized by NO synthases (NOSs) from arginine, which is a rate-limiting factor for NO production. We found that neuronal NOS (nNOS)-positive motor neurons were depleted while inducible NOS (iNOS)-positive activated glial cells were increased in transgenic mtSOD1 (G93A) ALS mice. iNOS expression was up regulated consistent with the increases of motor neuron loss and glial activation and citrulline and NO levels while nNOS expression was decreased in G93A ALS mice. Administration of l-arginine to G93A mice reduced the severity of motor neuron depletion and glial activation. In treated animals, nNOS expression was preserved while citrulline and NO were reduced, possibly due to reduced activation of glia expressing iNOS. Our findings show that high concentrations of NO correlate with iNOS expression rather than nNOS expression in G93A ALS mice. This suggests that therapy focused on iNOS inhibition might be a fruitful direction for future ALS therapeutic trials.

Ceftriaxone-Vancomycin Drug Toxicity Reduction by VRP 1020 in Mus musculus Mice

Drug toxicity is a common cause of liver injury and kidney failure. This study was designed to elucidate whether administration of high doses of Ceftriaxone or Vancomycin induce oxidative stress in liver as well as kidney, and to investigate the protective effects of VRP 1020 with fixed dose combination of ceftriaxone-vancomycin (Immunox-V). Twenty four Mus musculus mice (weighing 30 +/- 5 g) were divided into four groups containing six mice in each group. The activities of antioxidant enzymes such as superoxide dismutase, catalase and the level of malonaldialdehyde, as an marker of lipid per oxidation, were measured to evaluate oxidative stress in homogenates of the liver and renal tissue. Ceftriaxone or vancomycin administration significantly increased malonaldialdehyde levels (p < 0.001) but significant decreased in superoxide dismutase (p<0.01) and catalase (p<0.001) activities. Co-administration of VRP 1020 with FDC of Immunox-V injections caused significantly decreased malonaldialdehyde levels (p< 0.001) and increased superoxide dismutase (p<0.01) and catalase (p<0.001) activities in liver and renal tissue when compared with other treated groups. Similarly, the levels of extracellular antioxidant (Creatinine and Uric acid) were found to be significant lowered in Immunox-V treated group when compared to ceftriaxone or vancomycin alone treated group. These results indicate that chemical mediated technology of VRP 1020 with fixed dose combination of Immunox-V can prevent drug induced nephrotoxicity and oxidative stress which protects liver injury as well as renal tissue damage by reducing reactive oxygen species which improve the activities of free radical scavenging enzymes.