Transient increase in IL-1ß, IL-6 and TNF-α gene expression in rat liver exposed to gold nanoparticles.

Most studies have used in vitro systems to test inflammatory responses of nanoparticles; these may not reflect the real biological response of body organs. In fact, certain nanoparticles have provoked opposite effects under in vitro and in vivo conditions. Current understanding of the biocompatibility of gold nanoparticles is controversial. We studied the acute (1 day) and sub-chronic (5 days) effects of gold nanoparticles (10 and 50 nm in diameter) on expression of interleukin-1 beta (IL-1ß), IL-6 and tumor necrosis factor alpha (TNF-α) in rat liver. Real-time PCR analysis showed that gold nanoparticles of both sizes significantly increased cytokine gene expression on day 1; this had subsided by day 5. The 50-nm gold nanoparticle produced more severe inflammation than the smaller gold nanoparticle. These findings indicate a possible biocompatibility of medium-sized gold nanoparticles, as they caused only a transient increase in proinflammatory cytokines, followed by normalization during sub-chronic repeated exposure.

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.

Expression and localization of sPLA2-III in the rat CNS.

Phospholipases A(2) (PLA(2)) are enzymes that cleave the sn-2 bond of membrane phospholipids to yield free fatty acids and lysophospholipids. Secretory PLA2-III (sPLA(2)-III) has been suggested to be important for neuronal differentiation, growth and survival, and is highly expressed in the spinal cord. The aim of this study is to elucidate its expression and distribution in different regions of the adult rat CNS. Quantitative RT-PCR analyses showed high levels of sPLA(2)-III mRNA expression in the brainstem and spinal cord and low expression in the olfactory bulb. Western blot analyses showed high level of expression in the brainstem, spinal cord and cerebral neocortex. A dense band corresponding to the catalytically active, mature/cleaved form, and a faint band corresponding to the full length sPLA(2)-III were detected in post-mitochondrial supernatants, from different parts of the CNS. Subcellular fractionation of spinal cord homogenates showed that sPLA(2)-III protein is present in the 'light membrane/cytosol' fraction, but not the nucleus, synaptosomal membrane or synaptic vesicle-enriched fractions. sPLA(2)-III was immunolocalized to neurons in the cerebral neocortex, Purkinje neurons in the cerebellar cortex, periaqueductal gray, red nucleus, spinal trigeminal nucleus and dorsal horn of the spinal cord. Electron microscopy of the spinal cord and cerebral neocortex showed that sPLA(2)-III was localized in dendrites or dendritic spines, that formed asymmetrical synapses with unlabeled, putatively glutamatergic, axon terminals. The localization of mature/cleaved form of sPLA(2)-III in postsynaptic structures suggest a physiological role of the enzyme in neurotransmission or synaptic plasticity.

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.

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.

Effects of feeding periods of high cholesterol and saturated fat diet on blood biochemistry and hydroxyproline fractions in rabbits.

Hypercholesterolemia and hypertriglyceridemia are considered as important risk factors during the atherosclerotic process. The aim of the present investigation was to study the total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high density lipoprotein (HDL), triglyceride (TG), platelet levels and hydroxyproline fractions during the pathogenesis of atherosclerosis. For this purpose, twenty five 12-weeks, New Zealand white male rabbits, were purchased, individually caged, and divided into either control group or cholesterol-fed group. The control group (n = 10) was fed 100 g/day of normal diet, ORC-4 (Oriental Yeast Co. Ltd., Tokyo, Japan) for a period of 15 weeks. The cholesterol-fed group (n = 15) was fed a high cholesterol and saturated fat diet of ORC-4 containing 1% cholesterol plus 1% olive oil (100 g/day) for periods of 5 (group 1), 10 (group 2) and 15 (group 3) weeks. Blood sample from each animal was taken at the end of the experimental period for the biochemical analysis. The results of the present study showed that TC, LDLC, TG, HDLC and platelets were significantly (P < 0.01) increased in cholesterol-fed rabbits as compared with control rabbits. The serum hydroxyproline (Hyp) in rabbits belonging to group 1 showed no significant alteration when compared to control group. Group 2 rabbits showed a significant increase of 103% (P < 0.01) and 100% (P < 0.001) in free and protein-bound hydroxyproline fractions respectively when compared to control rabbits. However, there was no significant change in peptide-bound and total serum hydroxyproline levels as compared to the control group (P > 0.05). There was no significant (P > 0.05) decrease of free serum hydroxyproline in group 3 rabbits when compared to control rabbits. On the other hand, group 3 rabbits showed a significant increase in peptide-bound and protein-bound Hyp by 517% (P < 0.05) and 100% (P < 0.01) respectively when compared to control rabbits. However, total serum Hyp in group 3 rabbits showed no significant (P > 0.05) change when compared to control rabbits. These results suggest that feeding rabbits high cholesterol and saturated fat diet for feeding periods of 5, 10 and 15 weeks induced significant change in TC, LDLC, HDL, TG, platelet levels and various Hyp fractions in serum without any significant change in the total Hyp content.

Fluctuations in fasting blood glucose and serum fructosamine in pregnant women monitored on successive antenatal visits.

Fasting blood glucose (FBG) and serum fructosamine are simple and commonly used tests for monitoring diabetes mellitus. Unfortunately, both these parameters are associated with high error rates and therefore used with caution in high-risk populations. Setting high cut-off values for these parameters increases the sensitivity but at the cost of poor specificity (more false positives). Continued efforts have been made to evaluate the efficacy of FBG and fructosamine, singly or in combination, in avoiding a large number of unnecessary oral glucose tolerance tests (OGTT). Therefore, to better understand their time-course trends, we analysed FBG and c-fructosamine in 211 blood samples from 51 Saudi pregnant women during their multiple (> or =3) antenatal visits. The mean+/-standard deviation of FBG and c-fructosamine were 5.22+/-1.07 and 2.22+/-0.25 mmol/l respectively with a significant correlation between their individual values. Using the FBG cut-off >5.3 mmol/l, 19 subjects were classified as hyperglycaemic; this frequency was reduced to 1 when a FBG cut-off of >7.0 mmol/l was used. Combined values of FBG (>5.3 mmol/l) and c-fructosamine (>2.5 mmol/l) filtered 6 high-risk subjects with a prediction of gestational diabetes mellitus (GDM). Analysis of variance revealed high within-group variance for FBG. These fluctuations were also confirmed by higher coefficient of variations (CVs) for FBG (13.27%) as compared to c-fructosamine (5.49%). The CVs of FBG were not correlated with those of corresponding CVs of c-fructosamine (R = 0.007, P = 0.962), indicating that the fluctuations in FBG were independent of fluctuations in c-fructosamine. These findings clearly suggest that the paired values of FBG and c-fructosamine would be more advantageous than their individual values in filtering high-risk patients on whom OGTT should be performed.

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.

Oral theophylline changes renal carnitine palmitoyltransferase activity in rats.

BACKGROUND: Carnitine plays a critical role in lipid metabolism. Carnitine deficiency may adversely affect the oxidation of fatty acids and further aggravate abnormal lipid metabolism. Our objective was to investigate the effect of theophylline on the activity of carnitine palmitoyltransferase (CPT) in renal tissues of rats for 5-week-interval treatments. METHODS: The study was a randomized, controlled animal study. Theophylline was given at 100 mg/kg body weight (b.w.)/day and effects were monitored after a treatment period of between 1 and 5 weeks. RESULTS: Theophylline treatment caused a significant increase in renal CPT activity as compared to either control or placebo groups. Moreover, the results showed positive correlations between the renal concentration of long-chain acylcarnitine (LC), activity of CPT, urinary excretion of acylcarnitine (AC), and plasma concentration of LC (p <0.01), respectively. CONCLUSIONS: The observed changes in activity of renal CPT might be due to the result from theophylline-enhanced mobilization of lipid from adipose tissues that consequently stimulated an increased carnitine transport into the renal tissues to form palmitoylcarnitine groups for subsequent beta-oxidation inside the mitochondria. Thus, these accumulations of palmitoylcarnitine groups in mitochondria may increase the catalytic action of CPT.

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.

Evaluation of theophylline-stimulated changes in carnitine palmitoyltransferase activity in skeletal muscle and liver of rats.

The effect of theophylline treatments on the activity of carnitine palmitoyltransferase (CPT) in skeletal muscle and the liver of rats was investigated. Theophylline was administered at 100 mg/kg bw/day and effects were monitored after a treatment period that lasted between a week and five weeks. Results showed that a significant increase in the activity of CPT was observed in skeletal muscle of theophylline-treated groups as compared to either control or placebo groups. However, there was no significant change in the activity of CPT in the hepatic tissues of theophylline-treated groups. The observed discrepancies in activity of CPT might be due to the presence of two isoenzymes, the muscle type (M-CPT) and liver type (L-CPT); it is possible that theophylline affects only M-CPT activity.

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.

A study on distribution of different hydroxyproline fractions in the bovine ocular tissues.

The purpose of this study was to determine the content of total, free, peptide-bound, protein-bound, soluble- and insoluble collagen hydroxyproline (Hyp) in tissues of bovine eye. The results show that lens had the highest content of free Hyp. This was followed by cornea, retina, iris and aqueous humor. The difference between the Hyp content of lens and iris (p < 0.01) and aqueous humor (p < 0.001) was significant. The peptide-bound Hyp was highest in iris followed by cornea, ciliary body, sclera, lens, aqueous humor and retina. Significant differences (p < 0.001) was observed between the concentration of peptide-bound Hyp of iris and ciliary body, sclera, lens, aqueous humor and retina. Protein-bound Hyp was highest in iris, followed by ciliary body, sclera, cornea, lens, retina and aqueous humor. The difference between the protein-bound Hyp levels of iris and sclera, cornea, lens, retina and aqueous humor was significant (p < 0.001). No peptide-bound and protein-bound Hyp was detected in vitreous humor. Iris had the highest content of total Hyp. This was followed by cornea, ciliary body, sclera, lens, retina, vitreous humor and aqueous humor. The difference in the Hyp content of iris with ciliary body, sclera, lens, retina, vitreous humor and aqueous humor was significant (p < 0.001). Cornea had significantly (p < 0.001) higher content of soluble- and insoluble-collagen Hyp as compared to other tissues. This was followed by ciliary body, sclera, lens, iris and retina. Iris had the highest content of collagen. This was followed by cornea, ciliary body, sclera, lens, retina, vitreous humor and aqueous humor. The difference in the collagen content of iris with ciliary body, sclera, lens, retina, vitreous humor and aqueous humor was significant (p < 0.001).

Effect of tumor necrosis factor on hepatic oxidative stress and antioxidant defense indices in normal and Plasmodium yeolii nigeriensis infected mice.

BACKGROUND: Plasmodium yoelii nigeriensis (P. y. nigeriensis) produces lethal malaria infection in Swiss albino mice. Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide along with endogenously produced tumor necrosis factor (TNF) have been implicated in the pathogenesis of malaria. OBJECTIVE: Study the effect of TNF on hepatic oxidative stress and antioxidant defense indices in normal and P. y. nigeriensis infected mice. METHODS: Mice were divided into four groups. Normal group, TNF treated group, P. y. nigeriensis infected group, and P. y. nigeriensis infected mice treated with TNF group (250 microg/kg body weight, i.p.). RESULTS: TNF treatment of normal mice caused a highly significant decrease in hepatic superoxide dismutase (SOD) while changes in other oxidative stress and antioxidant defense indices were nonsignificant. On the other hand, TNF treatment of P. y. nigeriensis infected mice caused a highly significant increase in hepatic xanthine oxidase, lipid peroxidation and a significant decrease in hepatic SOD with respect to infected mice. CONCLUSION: These results suggest that exogenous TNF acts synergistically with P. y. nigeriensis infection to generate oxidative stress in the host and also causes an impairment of antioxidant defense enzyme such as superoxide dismutase.