Effects of alpha lipoic acid on acrylamide-induced hepatotoxicity in rats.

Acrylamide (ACR) is a neurotoxicant, reproductive toxicant, and carcinogen in animal species.  It is used in many industries and has been found to form naturally in foods cooked at high temperatures. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant whose therapeutic effect has been related to its antioxidant activity.  This study was carried out to study the protective effect of alpha lipoic acid on acrylamide induced perturbations in rat liver.  Four groups of rats were studied viz., control rats, acrylamide treated rats, alpha lipoic acid treated rats, and alpha lipoic acid plus acrylamide treated rats. ACR and ALA treatment alone and together caused a signifi-cant increase in hepatic reduced glutathione content while a decrease in hepatic ascorbic content was observed when compared to control group.  ALA pretreatment of acrylamide exposed rats caused no a signifi-cant alteration in superoxide dismutase activity but resulted in a tendency towards restoration of glutathione peroxidase and catalase activity to near normal levels.  Gel electrophoresis showed fragmentation of DNA in the treated groups.  The dose of ALA used in the present study afforded partial restoration of oxidative indices altered by ACR in rat liver.

Curcumin mediated attenuation of carbofuran induced toxicity in the heart of Wistar rats.

Carbofuran is used to improve the agricultural productivity as well as to protect the house hold and industrial products, but due to accumulation in the biological system, it causes serious side effects in many non-targets mammalian systems. The aim of present study is to evaluate the carbofuran induced oxidative stress in rat heart and its attenuation by using herbal product curcumin. Rats were divided into four groups; one group received 20 % LD50 of carbofuran another group of rats received same doses of carbofuran was  pretreated with curcumin (100 mg kg-1 body weight) and remaining two other groups served as control and curcumin treated animals. The activity of lactate dehydrogenase (LDH) in the heart tissues and serum was evaluated and the activity of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) was estimated in the heart tissues. The level of malondialdehyde (MDA) in heart tissues was also measured. The Total cholesterol (TC) and high density lipoprotein (HDL) was measured in the serum of the entire animals group. The results of present study showed that the activity of LDH in heart tissues were decreased and in serum was elevated. The MDA level was significantly elevated due to exposure of carbofuran. The enzymatic antioxidants, SOD and CAT activities were also inhibited. The ratio of pro-oxidant (P)/antioxidant (A) was also found to be sharply increased in the rat heart tissues of carbofuran exposed animals. The alterations in all the parameter were recovered by the pretreatment of curcumin (100 mg kg-1 body weight).

Effect of gold nanoparticles on superoxide dismutase and indoleamine 2, 3-dioxygenase in various rat tissues.

Gold nanoparticles have diverse applications and are being used in food and cosmetic industry, for drug delivery and in the diagnosis and treatment of cancer. However there is a need to study their biochemical mode of action. In this study, in vivo effect of gold nanoparticles on the activities of the two antioxidant enzymes -superoxide dismutase (SOD) and indoleamine 2,3-dioxygenase (IDO) was investigated in various tissues of rats. Rats were injected with 20 microg/kg body wt of 20 nm gold nanoparticles for three consecutive days through intraperitoneal route. The animals were sacrificed by CO2 asphyxiation 24 h after the last dose of gold nanoparticles. Results showed that treatment with gold nanoparticles caused no significant change in SOD activity in most of the tissues, except kidneys. In kidneys, gold nanoparticles caused a significant increase in SOD activity, when compared to the activity in control rats. However, treatment with gold nanoparticles altered the expression pattern of SOD activity in various tissues. For example, in control rats highest SOD activity was demonstrated in heart and least in kidneys and spleen. But, in gold nanoparticles treated rats, maximum SOD activity was observed in liver and the lowest in spleen. Gold nanoparticles caused no significant change in IDO activity in the studied tissues.

Expression and localization of duodenal cytochrome b in the rat hippocampus after kainate-induced excitotoxicity.

Brain iron accumulation and oxidative stress are common features of many neurodegenerative diseases, and could be due in part to increased iron influx across the blood-brain interface. The iron transport protein, divalent metal transporter 1 (DMT1) is found in reactive astrocytes of the lesioned hippocampal CA fields after excitotoxicity induced by the glutamate analog kainate (KA), but in order for iron to be transported by DMT1, it must be converted from the ferric to the ferrous form. The present study was carried out to investigate the expression of a ferric reductase, duodenal cytochrome b (DCYTB), in the rat hippocampus after KA injury. Quantitative reverse transcriptase-polymerase chain reaction showed significant increases in DCYTB mRNA expression of 2.5, 2.7, and 5.2-fold in the hippocampus at 1week, 2weeks and 1month post-KA lesions respectively compared to untreated controls, and 3.0-fold compared to 1month post-saline injection. DCYTB-positive cells were double labeled with glial fibrillary acidic protein, and electron microscopy showed that the DCYTB-positive cells had dense bundles of glial filaments, characteristic of astrocytes, and were present as end-feet around unlabeled brain capillary endothelial cells. DMT1 labeling in astrocytes and increased iron staining were also observed in the lesioned hippocampus. Together, the present findings of DCYTB and DMT1 localization in astrocytes suggest that DCYTB is a ferric reductase for reduction of ferric iron, for transport by DMT1 into the brain. We postulate that the coordinated action of these two proteins could be important in iron influx across the blood-brain interface, in areas undergoing neurodegeneration.

Pesticides-induced biochemical alterations in occupational North Indian suburban population.

Pesticides are used in agriculture to protect crops from insects-pests. Most of the field workers of North Indian population are exposed to commonly used insecticides. In the present study, pesticides induced oxidative stress as well as alterations in the level of acetylcholinesterase (AChE) in a total of 70 male healthy agricultural sprayers, exposed to pesticides for about 5 years, were studied and the results were compared with 70 controls. The levels of antioxidant enzymes (superoxide dismutase, CAT, glutathione-S-transferase and glutathione peroxidase), AChE, lipid peroxidation and glutathione (GSH) contents were determined in their blood erythrocytes (red blood cells (RBCs)). The results indicated significant increase in the levels of malondialdehyde as well as the activities of antioxidant enzymes in pesticide-exposed individuals. The levels of GSH, RBC-AChE activity and plasma antioxidant potential were sharply decreased when compared with control subjects. The ferric-reducing ability of plasma (FRAP) assay was carried out to evaluate the antioxidant potential of pesticide in exposed as well as healthy controls. A significant positive correlation was observed between plasma FRAP value and the activity of AChE from RBCs in pesticides sprayers. Furthermore, these results were supported by enhanced messenger RNA expressions of cytochrome P450 isoform 2E1 (CYP2E1) and gutathione-S-transferase isoform pi (GST-pi) in the white blood cells of the randomly selected pesticide-exposed individuals. The decreased GSH level in human red blood cells accompanied by increase in the levels of the activities of antioxidative enzymes and over expressions of CYP2E1 and GST-pi is an indicative of oxidative stress in pesticides-exposed individuals. The reduced activity of AChE indicates possible occurrence of perturbations in blood as well as neurotoxicity in pesticide sprayers.

Effect of sodium fluoride and magnesium chloride on different hydroxyproline fractions in rat liver.

Sodium fluoride (NaF) is used for prevention of caries in the form of fluoridated drinking water, fluoride tablets etc. In the present study, the effect of NaF-induced alterations in hydroxyproline (Hyp) and collagen was investigated in rat liver. The effect of pretreatment with MgCl2 on NaF-induced changes in liver Hyp and collagen was also studied. The NaF treatment at 5, 10 and 20 mg/kg body wt (reported LD50 of NaF being 24 mg/kg body wt through intraperitoneal route) caused a significant decrease in free Hyp (P < 0.05), when compared to control rats. The rats treated with 20 mg/kg body wt of NaF showed a significant increase in protein-bound Hyp (P < 0.001), as compared to control group, while of NaF treatment at 5 and 10 mg/kg body wt caused no significant change in protein-bound Hyp. All the doses of NaF had no significant effect on peptide-bound and total Hyp and total collagen. Treatment of with MgCl2 alone (30 mg/kg body wt) or with NaF (10 mg/kg body wt) caused a significant decrease in free Hyp (P < 0.05). MgCl2 alone and with NaF caused a significant increase (P < 0.05) in total collagen content. Thus, the present study demonstrated that NaF had no significant effect on total Hyp and collagen, indicating that its use in various products may not interfere with the liver collagen.

Effect of carbofuran on some biochemical indices of human erythrocytes in vitro.

Pesticides are used in agriculture to protect crops. Its widespread use in agriculture represents a threat not only to the environment but also to human populations exposed to them. Erythrocytes serve as an excellent model system to study the interaction of pro-oxidants. Organocarbamates are known to produce free radical species and to induce toxicity to different body systems resulting into hematological and biochemical perturbations. The information available relating to the effect of organocarbamates on the biochemical indices of human erythrocytes is scanty. Therefore, the present study was carried out to evaluate the impact of carbofuran, a carbamate pesticide, on some key biochemical indices of human erythrocytes' membrane. The oxidative potential of the pesticide was assessed in vitro by monitoring the levels of malondialdehyde (MDA) and reduced glutathione (GSH) in human erythrocytes exposed to different sub-acute concentrations (0, 2.5, 5, 10, 25 and 50µM) of carbofuran for different time intervals; maximally up to 120 min. It was observed that the level of MDA was elevated and that of GSH was significantly decreased after treatment of erythrocytes with carbofuran. The results indicated the negative impact of carbofuran in concentration and time dependent manner. Carbofuran was also found to sharply inhibit the activity of membrane bound Na(+)K(+)-ATPase at higher carbofuran concentrations (10, 25 and 50µM). Further, carbofuran at aforesaid concentrations was also found to cause significant rise in the osmotic fragility of human erythrocytes indicating adverse effect on membrane fluidity. The results of present study suggested that carbofuran was able to alter the oxidative balance and the stability of human erythrocytes membrane.

A study on the distribution of different carnitine fractions in various tissues of bovine eye.

The aim of the present investigation was to study the distribution of various carnitine fractions in different bovine ocular tissues. Different ocular tissues were homogenized and their carnitine content was determined. The carnitine fractions studied include short chain carnitine, long chain carnitine, acyl carnitine and free carnitine. All the four carnitine fractions were found to be present in all the ocular tissues studied. Iris contained the highest concentration short chain, long chain and acyl carnitine. However significant (p < 0.05) differences existed in long chain and acyl carnitine between iris and other tissues. Free carnitine was found in highest concentration in ciliary body which was significantly higher when compared to lens nucleus (p < 0.05). There was no significant difference in the carnitine fractions between aqueous and vitreous humor. These results show differential distribution of carnitine in bovine ocular tissues which may be involved in various functions besides fatty acid oxidation.

Effect of different doses of sodium fluoride on various hydroxyproline fractions in rat serum.

Human beings are exposed to fluoride through its occurrence in the environment and its presence in various products. The present study was carried out to study the effect of acute doses of sodium fluoride on the body collagen in rats. To evaluate this effect the concentration of collagen breakdown products like different hydroxyproline fractions were determined in serum following the exposure of rats to various concentrations of sodium fluoride. 5 and 10 mg/kg weight dose of NaF caused no significant change in total hydroxyproline but caused significant changes in some of the hydroxyproline fractions. However higher doses of NaF viz., 20 and 30 mg/kg body weight caused significant changes in different hydroxyproline fractions and also a significant decrease in total hydroxyproline indicating the probability of collagen formation in some tissues.

Protective effect of magnesium chloride on sodium fluoride induced alterations in various hydroxyproline fractions in rat lungs.

Frequent absorption of the fluoride causes tooth decay, damage of kidneys, bones, nerves and muscles. The present study was carried out to study the reported protective effect of magnesium chloride on sodium fluoride (NaF) induced alterations in rat lung hydroxyproline/ collagen content. To study the dose response of NaF following groups were studied: (i) normal rats (ii) placebo group, (iii) rats treated with two different doses of NaF. To study the protective effect of MgCl2 the following groups of rats were studied (i) normal rats (ii) rats injected with MgCl2 (iii) rats injected with NaF (iv) rats injected with MgCl2 followed by NaF. Sodium fluoride doses of 10 and 20 mg/kg body weight of rats caused a significant increase (p < 0. 001) increase in peptide- bound and total Hyp content in rat lungs. Administration of MgCl2 alone to rats also caused significant increase in peptide- bound, protein- bound and total Hyp fractions in rat lungs (p < 0. 001). Administration of MgCl2 thirty minutes before NaF restored the altered protein bound Hyp fraction to almost normal levels. The present study concludes that although MgCl2 has been reported to be protective against toxic effects of NaF, it exerts an independent effect on hydroxyproline and collagen content in rat lungs.

The changes in various hydroxyproline fractions in aortic tissue of rabbits are closely related to the progression of atherosclerosis.

BACKGROUND: The most important function of collagen and elastin is to induce several mechanical parameters which are known to play a dominant role in governing mechanical properties of the blood vessels. The aortic tissue of rabbit is one of the important sources of collagen and elastin. The effects of high fat diet (HFD) on the hydroxyproline (Hyp) fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits have not been documented before. The present study was undertaken to investigate the changes in Hyp fractions in serum and aortic tissues of rabbits and collagen content in the aortic tissues of rabbits during the progression of atherosclerosis. The atherosclerotic model used in this study was the New Zealand white rabbit (male; 12 weeks old). Twenty five rabbits were individually caged, and divided into control group (NOR; n = 10) and HFD group (CHO; n = 15). The control group was fed (100 g/day) of normal (NOR) diet for a period of 15 weeks. The HFD group was fed normal diet supplemented with 1.0% cholesterol plus 1.0% olive oil (100 g/day) for the same period of time. RESULTS: We found that the TC, LDLC, and TG (mg/dl) were significantly (p < 0.001) increased in HFD rabbits compared with control rabbits with percentage normalized changes of 1198%, 1591%, and 710%, respectively. The peptide-bound Hyp in the serum was significantly (P < 0.05) increased in HFD rabbits compared with control rabbits with percentage normalized change of 517% while it significantly (P < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 65%. The protein-bound Hyp in the serum was significantly (P < 0.01) increased in HFD rabbits compared with control rabbits with percentage normalized change of 100%; the protein-bound Hyp in the aortic tissues of control rabbits was 235.30 +/- 55.14 (Mean +/- SD) while it was not detectable (ND) in HFD rabbits. Total serum Hyp showed no significant (P < 0.05) change in HFD rabbits compared with control rabbits while it was significantly (P < 0.05) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73%. The total collagen was significantly (p < 0.01) decreased in aortic tissues of HFD rabbits compared with control rabbits with percentage normalized change of 73% which was supported by histological study. CONCLUSIONS: These results suggest that percentage decrease in various Hyp fractions in aortic tissue of HFD rabbits are closely related to percentage decrease of collagen content in aortic tissues of HFD rabbits. These results also suggest that it may be possible to use the changes in various Hyp fractions in aortic tissues of rabbits as an important risk factor during the progression of atherosclerosis.

Presurgical, ultrasound-guided anchor-wire marking of impalpable cervical lymph nodes.

This case illustrates the surgical use of wire localization, a well tried technique from a different field of surgery, in the removal of an ultrasound-detected, impalpable deep lower cervical lymph node in a high-risk patient. A localization needle with an echogenic tip was placed freehand under ultrasound guidance, immediately before surgery. The imaging and marking of the impalpable cervical lymph node resulted in a precise surgical dissection and a reduction in operating time whilst minimizing risks to the patient and staff.

Effect of mercuric chloride on various hydroxyproline fractions in rat serum.

Mercuric chloride (HgCl2) disturbs the collagen metabolism in the body which is reflected by altered hydroxyproline fractions in the serum. The aim of the present investigation was to study the effect of HgCl2 treatment on various hydroxyproline (Hyp) fractions in rat serum and the effect of 2,3-dimercapto-1-propane sulfonic acid (DMPS) treatment on serum Hyp fractions in HgCl2 treated rats. Other parameters studied included body weight, food intake, water intake and kidney weight. Doses of HgCl2 used were 0.1, 0.5, 1.0, 2.0, 3.0 mg/kg body weight and that of DMPS was 100 mg DMPS/kg body weight. All the doses of HgCl2 used caused significant (p < 0.01) alterations in free, peptide-bound and protein-bound Hyp in the serum when compared with control rats but a dose of 2 mg/kg body weight caused significant (p < 0.001) alteration even in the total serum Hyp when compared to control rats. Administration of DMPS prior HgCl2 treatment of rats sacrificed 24 h after the treatment caused a significant decrease of 52% (p < 0.01) in free Hyp when compared to similar HgCl2 treated rats. DMPS treatment with HgCl2 also caused an increase of 61% (p < 0.001) and 114% (p < 0.001) in peptide- and protein-bound Hyp respectively, when compared to HgCl2 treated rats sacrificed 24 h after mercuric chloride and DMPS treatment. Administration of DMPS followed by HgCl2 to rats which were sacrificed 48 h later caused no significant change in the total and free Hyp when compared to HgCl2 treated rats which were sacrificed 48 h after the treatment. But there was a significant decrease of 40% (p < 0.001) in peptide-bound Hyp and an increase in of 77% (p < 0.001) in protein-bound Hyp when compared to HgCl2 treated rats sacrificed 48 h after the treatment. The present study shows that HgCl2 treatment caused significant alterations in serum Hyp fractions reflecting disturbed composition of connective tissues which were not reversed by DMPS treatment.

Hydroxyproline concentrations in ocular tissues of Arabian camel (Camelus dromedarius Linn.).

Hydroxyproline (Hyp) concentrations (total, free, peptide-bound and protein-bound) in camel eye tissues were determined. Total Hyp concentration was highest in iris, followed by ciliary body, sclera, cornea, lens and retina; the difference between total Hyp concentration of iris and sclera (P < 0.05) and cornea, lens and retina (P < 0.001) was statistically significant. Cornea had the highest concentration of free Hyp, followed by ciliary body, retina, iris, sclera and lens (P < 0.001). Peptide-bound Hyp concentration was highest in iris, followed by lens, cornea, ciliary body, retina and sclera (P < 0.001). Iris also had the highest concentration of protein-bound Hyp, followed by ciliary body, sclera, cornea, retina and lens; the difference in the protein-bound Hyp concentration between iris and sclera (P < 0.05) and cornea, retina and lens (P < 0.001) was statistically significant. Iris was also found to have the highest concentration of collagen, followed by ciliary body, sclera, cornea, lens and retina; the difference between the collagen concentration of iris and sclera (P < 0.05) and cornea, lens and retina (P < 0.001) was statistically significant. These variations may result from differences in the collagen structure and/or composition in these tissues.

Hydroxyproline distribution in the plasma of various mammals.

We have investigated the presence of total, free, protein-bound and peptide-bound hydroxyproline (Hyp) in the plasma of different mammals viz., camel, bovine, sheep, human, rabbit and rat. Total Hyp was significantly highest in human followed by rabbit, rat, bovine, sheep and camel (P<0.001). Free Hyp was significantly highest in human followed by rabbit, rat, camel, bovine and sheep (P<0.001). However, the protein-bound Hyp content was significantly highest in rat followed by bovine, human, camel, rabbit and sheep (P<0.001). Peptide-bound Hyp was significantly highest in human plasma followed by sheep and rabbit (P<0.001). No peptide-bound Hyp was detected in the plasma of camel, bovine or rat. In the human plasma, peptide-bound Hyp constituted 60% of the total plasma Hyp, followed by protein-bound Hyp, which was 35% of the total, Hyp and free Hyp, which was 15% of the total plasma Hyp. In the sheep plasma peptide-bound Hyp constituted about 50% of total Hyp followed by protein-bound (40% of the total Hyp) and free Hyp, which formed 10% of total Hyp. In the rabbit plasma protein-bound Hyp constituted 50% of the total Hyp fraction, followed by peptide-bound and free, which constituted about 30 and 20%, respectively, of the total Hyp fraction of the plasma. Peptide-bound Hyp formed 92, 84 and 82% of the total plasma Hyp in rat, camel and bovine, respectively. Free Hyp constituted about 8% of the total plasma Hyp in rat and 18% of total Hyp in bovine and camel, respectively. The causes of the significant variations in different collagen structure and composition with respect to the different species examined are not known, however, these variations may results from differences in turn-over rate of Hyp in those species.

Antagonist effect of chloroquine and tumor necrosis factor on hepatic oxidative stress and antioxidant defense in normal and Plasmodium yoelii nigeriensis-infected mice.

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Tumor necrosis factor (TNF) has been implicated in the pathogenesis of malaria by production of reactive oxygen species. Chloroquine is a traditionally used antimalarial and has been postulated to inhibit TNF secretion during malaria infection. OBJECTIVE: The study the comparative effect of chloroquine and TNF treatment on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis-infected mice. MATERIALS AND METHODS: The mice were divided into six groups, each consisting of four to six animals. They were normal mice, normal mice treated with chloroquine, normal mice treated with TNF-alpha, P. y. nigeriensis-infected mice, P. y. nigeriensis-infected mice treated with chloroquine and P. y. nigeriensis-infected mice treated with TNF-alpha. RESULTS: Chloroquine treatment of the normal mice caused no significant alterations in hepatic oxidative stress and antioxidant defense indices while TNF treatment of normal mice caused a significant decrease in hepatic superoxide dismutase. Chloroquine treatment of P. y. nigeriensis-infected mice caused a decrease in blood parasitemia which was accompanied by restoration of altered indices to near normal levels. However, TNF treatment of P. y. nigeriensis-infected mice had no effect on blood parasitemia but caused a significant increase of hepatic xanthine oxidase and lipid peroxidation and a decrease in the activity of hepatic superoxide dismutase. CONCLUSION: Exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of the antioxidant defense enzyme SOD, while chloroquine treatment reduces the severity of malaria infection by decreasing the blood parasitemia and also perhaps by inhibiting the TNF release.

Methemoglobin reductase activity and in vitro sensitivity towards oxidant induced methemoglobinemia in swiss mice and beagle dogs erythrocytes.

The NADH methemoglobin-reductase (EC 1.6.2.2) is mainly responsible for the maintenance of hemoglobin in its reduced and active state. The present study reveals the comparative status of this enzyme in normal Beagle dogs, rats, mice, mastomys and hamsters erythrocytes. The spectrophotometric and electrophoretic determinations showed that the above mentioned enzyme was deficient in the Beagle dog's erythrocytes. Furthermore, in vitro studies on the sensitivity of these rodents and Beagle dogs hemolysate towards oxidants, like primaquine and sodium nitrate, depicted a higher level of methemoglobin formation in the Beagle dogs hemolysate as compared to that of the rodent species. The deficiency of methemoglobin reductase in Beagle dogs erythrocytes could be responsible for their increased sensitivity towards oxidant induced methemoglobinemia.

Changes in rodent-erythrocyte methemoglobin reductase system produced by two malaria parasites, viz. Plasmodium yoelii nigeriensis and Plasmodium berghei.

The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin and methemoglobin in blood. Exposure of red blood cells to oxidative stress (pathological/physiological) may cause impairment to this equilibrium. We studied the status of erythrocytic methemoglobin and the related reductase system during Plasmodium yoelii nigeriensis infection in mice and P. berghei infection in mastomys. Malaria infection was induced by intraperitoneal inoculation with 10(6) infected erythrocytes. The present investigation revealed a significant decrease in the activity of methemoglobin reductase, with a concomitant rise in methemoglobin content during P. yoelii nigeriensis infection in mice erythrocytes. This was accompanied with a significant increase in reduced glutathione and ascorbate levels. The activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase increased with a progressive rise in parasitemia. However, no methemoglobin or associated reductase activity was detected in normal and P. berghei-infected mastomys. P. berghei infection in mastomys resulted in an increase in the level of reduced glutathione and ascorbate in erythrocytes, and also in the activity of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase. These results suggest that antioxidants/antioxidant enzymes may prevent or reduce the formation of methemoglobin in the host and thereby protect the host from methemoglobinemia.

Effect of beta-arteether treatment on erythrocytic methemoglobin reductase system in Plasmodium yoelii nigeriensis infected mice.

BACKGROUND: The methemoglobin reductase system plays a vital role in maintaining the equilibrium between hemoglobin (Hb) and methemoglobin (MetHb) in blood. Exposure of red blood cells to an oxidative stress (pathological/physiological) may cause impairment in this equilibrium. OBJECTIVE: The status of MetHb and the related reductase system was studied during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and beta-arteether treatment in mice. METHODS: Mice were divided into four groups. Normal group, normal mice treated with beta-arteether, P. y. nigeriensis infected mice and P. y. nigeriensis infected mice treated with beta-arteether. RESULTS: The present investigation revealed a marked decrease in the activity of MetHb reductase, with concomitant rise in MetHb levels during P. y. nigeriensis infection in mice erythrocytes (P < 0.001) as compared to normal mice. However, the activities of the associated enzymes viz., lactate dehydrogenase, glucose 6-phosphate dehydrogenase and glutathione reductase were found to be increased with progressive rise in parasitemia. beta-Arteether treatment (12.5 mg/kg body weight) of infected mice (parasitemia 20-25%) from day 5 of post infection resulted in complete clearance of parasitemia on day 7 of post infection, which was accompanied by restoration of all the altered above mentioned indices to near normal levels as compared to infected mice (P < 0.001). CONCLUSION: These results suggest that there is a marked impairment of methemoglobin and methemoglobin reductase system during P. y. nigeriensis infection in mice. beta-Arteether treatment of infected mice resulted in complete clearance of parasitemia which also caused the restoration of methemoglobin and methemoglobin reductase system to near normal levels.

Effect of poly ICLC treatment on hepatic oxidative stress and antioxidant defense indices in Plasmodium yoelii nigeriensis infected mice.

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) are important mediators of tissue injury during malaria infection. OBJECTIVE: To study the status of hepatic oxidative stress and antioxidant defense indices during Plasmodium yoelii nigeriensis (P. y. nigeriensis) infection and poly ICLC treatment of normal and P. y. nigeriensis infected Swiss albino mice. METHODS: Mice were divided into four groups viz., 1. Normal mice, 2. Normal mice treated with poly ICLC (5 mg/kg body weight, i.p.), 3. P. y. nigeriensis infected mice and 4. P. y. nigeriensis infected mice treated with poly ICLC (5 mg/kg body weight, i.p.). RESULTS: P. y. nigeriensis infection caused a significant increase in hepatic oxidative stress indices viz., xanthine oxidase and lipid peroxidation. This was accompanied by a significant increase in antioxidant defense indices viz., reduced glutathione (GSH), glutathione reductase while superoxide dismutase and catalase showed a significant decrease with respect to normal mice. Poly ICLC treatment of P. y. nigeriensis infected mice did not cure blood parasitemia. However, poly ICLC treatment of normal and P. y. nigeriensis resulted in an increased generation of hepatic oxidative stress and an associated increase in the antioxidant defense indices. CONCLUSION: poly ICLC therapy alone is not sufficient to treat the malaria infection caused by multiple drug resistant strain of P. y. nigeriensis. Therefore there is a need to develop newer antimalarias which can act alone or in combination with traditional antimalarials to be effective against drug resistant malarial parasite.