Ascorbic Acid Levels in Avian Tissues and Its Metabolic Significance

The site of localization and concentration of ascorbic acid (AA) in a number of tissues of the pigeon were studied by a modified histochemical method coupled with cytophotoelectrometric determinations. It was evident from the data that significant variations were found in AA concentrations of different tissues of the pigeon. The brain possessed the highest content of AA/cell. The liver, ovary, pancreatic acini, kidney, adrenal and testis followed in order, whereas, the pancreatic islet region was the poorest in AA. On the basis of the synchronization of the high AA content of these tissues with their well known high level of metabolic activity, it is suggested that AA participates in the metabolic turnover by serving as an electron donor via the formation of its free radical. Considering the fact that these organs are very rich in ascorbic acid, there is also a possibility for the biosynthesis of AA in tissues like the liver and kidney of the pigeon as in other bird species. The need for further work in this direction is stressed.     

Association of Liposome-Encapsulated Trivalent Antimonial with Ascorbic Acid: An Effective and Safe Strategy in the Treatment of Experimental Visceral Leishmaniasis

Background:

Visceral leishmaniasis (VL) is a chronic debilitating disease endemic in tropical and subtropical areas, caused by protozoan parasites of the genus Leishmania. Annually, it is estimated the occurrence of 0.2 to 0.4 million new cases of the disease worldwide. Considering the lack of an effective vaccine the afflicted population must rely on both, an accurate diagnosis and successful treatment to combat the disease. Here we propose to evaluate the efficacy of trivalent antimonial encapsulated in conventional liposomes, in association with ascorbic acid, by monitoring its toxicity and efficacy in BALB/c mice infected with Leishmania infantum.

Methodology/Principal Findings:

Infected mice were subjected to single-dose treatments consisting in the administration of either free or liposome-encapsulated trivalent antimony (SbIII), in association or not with ascorbic acid. Parasite burden was assessed in the liver, spleen and bone marrow using the serial limiting dilution technique. After treatment, tissue alterations were examined by histopathology of liver, heart and kidney and confirmed by serum levels of classic biomarkers. The phenotypic profile of splenocytes was also investigated by flow cytometry. Treatment with liposome-encapsulated SbIII significantly reduced the parasite burden in the liver, spleen and bone marrow. Co-administration of ascorbic acid, with either free SbIII or its liposomal form, did not interfere with its leishmanicidal activity and promoted reduced toxicity particularly to the kidney and liver tissues.

Conclusions/Significance:

Among the evaluated posological regimens treatment of L. infantum-infected mice with liposomal SbIII, in association with ascorbic acid, represented the best alternative as judged by its high leishmanicidal activity and absence of detectable toxic effects. Of particular importance, reduction of parasite burden in the bone marrow attested to the ability of SbIII-carrying liposomes to efficiently reach this body compartment.     

Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.     

Antioxidant levels in tissues of young and adult camels (Camelus dromedarius)

In this study, we measured the concentration of some antioxidant substances in erythrocytes hemolysate, liver, kidney and brain in young and adult camels. It has been found that the activity of the antioxidant enzymes glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and the concentration of glutathione, ascorbic acid and alpha-tocopherol are high in both young and adult camels. GSH-Px and CAT activities were higher in adult camels than in the young whereas no significant difference in the activity of SOD between young and adult camels was noticed. Glutathione was present in all tissues studied. Ascorbic acid was found to have significantly higher values in young camels. From this study it could be concluded that, as in other mammals, camel tissues contain a powerful antioxidant system. The liver has the highest contents of antioxidants and antioxidant enzymes indicating that it plays an important role in pro-oxidants detoxification. Age has a variable effect on the antioxidant system in camels.     

Detection of metabolic conversions of ascorbate-2-monophosphate and ascorbate-2-sulfate to ascorbic acid in tiger prawn (Penaeus monodon) using high-performance liquid chromatography and colorimetry

Biochemical conversions of ascorbate-2-monophosphate and ascorbate-2-sulfate to ascorbic acid by acid phosphatase and ascorbate-2-sulfate sulfohydrolase, respectively, were found in extracts of a hepatopancreas of Penaeus monodon, bovine liver and tilapia liver. Both enzymes were assayed with high-performance liquid chromatography (HPLC) and colorimetry. Colorimetry was based on the reduction of a color of 2,6-dichlorophenolindophenol (DCIP) when ascorbic acid was released from enzymatic activity. Assay of acid phosphatase either with HPLC or with colorimetry was found to be equally reliable. However, sensitivity of the HPLC assay was slightly higher than that of colorimetry; HPLC was able to detect activity as little as 1 nmol ascorbic acid released per min, whereas colorimetry was limited at 6–7 nmol/min. Assay of ascorbate-2-sulfate sulfohydrolase in crude extracts with the HPLC technique was found to be more specific than that with the colorimetric assay. The excess reduction of DCIP color not related to the sulfohydrolase activity was observed in the colorimetric technique. An accumulation of ascorbic acid in a hepatopancreas of P. monodon fed with feeds supplemented with phosphorylated or sulfated ascorbic acid was higher than that of the prawn fed with feed without ascorbic acid. The accumulated ascorbic acid was possibly from the activity of acid phosphatase or the sulfohydrolase that hydrolyzed phosphorylated or sulfated derivatives in vivo, respectively. Metabolism of the ascorbate derivatives in the prawn is discussed.     

Effect of aging on aqueous-phase antioxidants in tissues of male Fischer rats

The purpose of this study was to determine the influence of aging on concentrations of the important aqueous-phase antioxidants in rat tissues. Ascorbic acid, glutathione and uric acid were measured in tissues and organs of male Fischer 344 rats at 6, 15 and 26 months of age. Blood, liver, lungs, heart, kidneys, brain, testes and lenses were excised rapidly and were extracted with cold metaphosphoric acid. Aging diminished the concentration of ascorbic acid in liver, lung and lens; levels in 26-month-old rats were 40-60% of those in 6-month-old rats. Glutathione content was diminished only in lens, where it decreased almost 50% between 15 and 26 months. Some age-associated increases in antioxidant levels also were seen; testis ascorbic acid and kidney glutathione levels were elevated in the old compared with the younger rats. Uric acid concentrations were much lower than glutathione or ascorbic acid concentrations in every tissue except plasma. Old rats had lower levels of uric acid in liver but higher levels in heart, kidney and testis. These results demonstrate that aqueous-phase antioxidant levels are not uniformly diminished in tissues of old rats.     

Therapeutic potentials of combined use of DMSA with calcium and ascorbic acid in the treatment of mild to moderately lead intoxicated mice

The aim of this study was to explore the therapeutic efficacies of combined use of meso-2,3-dimercaptosuccinic acid (DMSA) with calcium and ascorbic acid in the treatment of mild to moderately lead-intoxicated mice. Female albino mice were exposed to lead by drinking water contaminated with 0.1% (moderate lead exposure) or 0.05% (mild lead exposure) lead acetate. After the cessation of lead exposure, mice were supplemented by gavage with saline solution, 50 mg/kg body weight (b.w) DMSA, 100 mg/kg b.w DMSA, calcium and ascorbic acid, or 50 mg/kg b.w DMSA and calcium as well as ascorbic acid, respectively. Atomic absorption spectrophotometric method was used to analyze lead levels in blood, bone, liver, kidney and brain. Activities of blood δ-aminolevulinic acid dehydratase (ALAD) were determined by colorimetric method. DMSA supplemented alone could reduce lead levels in both soft tissues and bone and reverse lead-inhibited activities of blood ALAD in mild to moderately lead-intoxicated mice. On the other hand, combined use of DMSA with calcium and ascorbic acid achieved better therapeutic efficacies in mobilizing lead in blood, liver and kidney, and reversing lead-inhibited activities of blood ALAD in moderately lead intoxicated mice than DMSA supplemented alone. Moreover, the better therapeutic efficacies were also found in mildly lead intoxicated mice in mobilizing lead in blood and bone achieved by combined use of DMSA with calcium and ascorbic acid. Combined use of DMSA with calcium and ascorbic acid seems to be the better choice in the treatment of mild to moderate lead-intoxication.     

Comparative tissue ascorbic acid studies in fishes

Comparative tissue ascorbic acid levels in four species of major carp viz., Labeo rohila, L. calbasu, Cirrhina tnrigala and Catla catla , were investigated. The ascorbic acid level was found to be the highest in the spleen in the four species studied (range 430–380 μg/g) followed by the anterior (adrenal) kidney, gonads, liver, renal kidney, brain and/or eye. Heart and blood had the lowest levels (range 26–18 μg/ml) amongst the tissues studied. Overall tissue ascorbic acid levels were the highest in L. rohita and the lowest in C. mrigala . Investigation on seasonal variations in blood and kidney ascorbic acid levels of Notopterus notopterus revealed peak levels in spring (February-April) and the lowest levels in the postspawning period (August-September).     

Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid,teas and fruit juices

The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.     

Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers

The effects of cadmium on performance, antioxidant defense system, liver and kidney functions, and cadmium accumulation in selected tissues of broiler chickens were studied. Whether the possible adverse effects of cadmium would reverse with the antioxidant ascorbic acid was also investigated. Hence, 4 treatment groups (3 replicates of 10 chicks each) were designed in the study: control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic acid was added to the basal diet at 200 mg/kg either alone or with cadmium. Cadmium decreased the body weight (BW), body weight gain (BWG), and feed efficiency (FE) significantly at the end of the experiment, wheras its effect on feed consumption (FC) was not significant. Cadmium increased the plasma malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate amino transferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT) activities were not changed by cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys, liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a reduction of MDA level previously increased by cadmium and a restoration in SOD activity. However, ascorbic acid did not ameliorate the growth inhibitory effect of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These data indicate that oxidative stress, induced by cadmium, plays a role in decreasing the performance of broilers and that dietary supplementation by ascorbic acid might be useful in reversing the lipid peroxidation induced by cadmium and partly alleviating the adverse effect of cadmium on performance of broilers.     

Effects of diet and of alloxan-diabetes on the activity of branched-chain 2-oxo acid dehydrogenase complex and of activator protein in rat tissues.

The total activities (sum of active and inactive forms) of branched-chain 2-oxo acid dehydrogenase complex in tissues of normal rats fed on a standard diet were (unit/g wet wt.): liver, 0.82; kidney, 0.77; heart, 0.57; hindlimb skeletal muscles, 0.034. Total activity was decreased in liver by 9%- or 0%-casein diets and by 48 h starvation, but not by alloxan-diabetes. Total activities were unchanged in kidney and heart. The amount of active form of the complex (in unit/g wet wt. and as % of total) in tissues of normal rats fed on standard diet was: liver, 0.45, 55%; kidney, 0.55, 71%; heart, 0.03, 5%; skeletal muscle less than 0.007, less than 20% (below lower limit of assay). The concentration of the active form of the complex was decreased in liver and kidney, but not in heart, by low-protein diets, 48 h starvation and alloxan-diabetes. In heart muscle alloxan-diabetes increased the concentration of active complex. The concentration of activator protein (which activates phosphorylated complex without dephosphorylation) in liver and kidney was decreased by 70-90% by low-protein diets and 48 h starvation. Alloxan-diabetes decreased activator protein in liver, but not in kidney. Evidence is given that in tissues of rats fed on a normal diet approx. 70% of whole-body active branched chain complex is in the liver and that the major change in activity occasioned by low-protein diets is also in the liver.     

An improved assay technique for uridine diphosphate glucuronosyltransferase activity towards 5-hydroxytryptamine and some properties of the enzyme.

A simplified and sensitive procedure for the routine assay of UDP-glucuronosyltransferase activity towards 5-hydroxytryptamine (serotonin) was developed and the reaction product confirmed as the O-glucuronide of this substrate. The assay was used to study some properties of this UDP-glucuronosyltransferase activity. In mouse liver activity was stimulated by membrane-perturbation procedures and by UDP-N-acetylglucosamine. In rat liver it was stimulated by digitonin, but not by diethylnitrosamine. Mouse duodenum, kidney, and lung possessed activity that was less latent than in liver. No activity was found in homogenates of brain. The activity was present in Gunn rat liver, though only one-third of that in Wistar rat liver. Cat liver contained no UDP-glucuronosyltransferase activity towards 5-hydroxytryptamine.     

Ascorbic acid status of mullet, Mugil cephalus Linn., exposed to cadmium

The effects of acute and chronic cadmium exposures on ascorbic acid concentrations and cadmium accumulation in the tissues of juvenile mullet, Mugil cephalus , are described. Hepatic ascorbic acid reserves were maintained in untreated mullet fed a diet containing ascorbate, but decreased 60% in individuals exposed to 10 mg Cd 1^-1 for six weeks. Ascorbic acid depletion was accompanied by a massive accumulation of cadmium in the liver. Similar changes were found in gill tissue. In contrast, ascorbic acid concentrations were largely unaffected in kidney tissue which had a limited capacity to accumulate the metal. There were marked fluctuations of ascorbic acid levels in the brain. Only small amounts of cadmium were accumulated by this tissue. These results indicate that in mullet liver, gill and brain ascorbic acid stores may be depleted during chronic cadmium poisoning.     

Ascorbic acid and aging in the rat. Uptake of ascorbic acid by teeth and concentration of various forms of ascorbic acid in different organs

1. The uptake of ascorbic acid in vitro by the teeth of rats showed a gradual decrease with age, indicating that the uptake may be related to collagen synthesis as in bone. 2. The concentration of total free ascorbic acid in various organs declined with age, but the rate of decline was different in different organs. In the spleen, however, it increased until maturity and then declined. 3. This decrease may be due to one or both of the following reasons: (a) the permeability of different tissues may decrease at different rates for ascorbic acid, or (b) the requirement for ascorbic acid may decrease at different rates. 4. The bound ascorbic acid declined with age in the skin, kidney, liver and brain after the age of 10-12 weeks, and in the spleen after the age of 26 weeks. 5. The concentration of dehydroascorbic acid and dioxogulonic acid declined with age in the skin.     

THE DISTRIBUTION OF GLUTAMATE DECARBOXYLASE IN RAT TISSUES; ISOTOPIC VS FLUORIMETRIC ASSAYS

—The activity of glutamate decarboxylase (GAD, EC 4.1.1.15) in normal and neoplastic rat tissues was determined by two assay methods, one based on the production of ¹⁴CO₂ from [¹⁴C]glutamic acid and the other on the fluorimetric measurement of γ-aminobutyric acid (GABA) formation. Activities obtained with the isotopic assay were high in every tissue (ranging from over 800 in liver and brain to 107nmol CO₂/min/g in lung). They were drastically diminished by Triton X-100, by an oxygen-free atmosphere or by the mitochondrial electron transport inhibitors, rotenone and antimycin A. Activities measured fluorimetrically were significant in only a few tissues and were stimulated by Triton (e.g. from 299 to 569 nmol GABA/min/g brain) but were unaffected by rotenone. For several tissues after Triton treatment the fluorimetric and isotopic assays (in air) gave the same results (i.e. the two end products, CO₂ and GABA were in stoichiometric agreement); however, the fluorimetric assay remains the more reliable measure of GAD activity since Triton may not inhibit completely the non-GAD dependent decarboxylation of glutamate in all types of tissue preparations. The hepatic, renal and mammary tumours tested were devoid of GAD; among non-neural normal tissues, kidney, liver and, possibly, adrenal gland contained significant GAD activity. In kidney and liver the activity was 15 and 10 per cent of that in brain.     

Tissue distribution of L-fucokinase in rodents

L-fucose (fucose) is a monosaccharide normally present in mammals and is unique in being the only levorotatory sugar that can be synthesized and utilized by mammals. The metabolism of fucose is incompletely understood, but fucose can be synthesized de novo or salvaged. The utilization of fucose in the salvage pathway begins with phosphorylation by fucokinase. As part of an investigation of fucose metabolism in normal and disease states, we began an investigation of this enzyme. In this report, we present the tissue distribution of the enzyme in rat and mouse. The highest amount of activity was present in brain of both species. Some activity was found in all tissues examined (liver, kidney, heart, lung, spleen, brain, muscle, thymus, white adipose, testes, eye, aorta, small intestine, and submaxillary gland). Very low levels were found in small intestine. Varying levels in the tissues seems most likely to be the result of varying amounts of fucokinase protein as no difference in the Km values of crude enzyme could be shown. Protein-bound fucose levels were determined using the L-cysteine-phenol-sulfuric acid (CPS) assay. There is not a good correlation between fucokinase activity and protein-bound fucose, suggesting some tissues are more active in synthesis of fucose than others.     

The primary localization of ascorbate and its synthesis in the kidneys of acipenserid (Chondrostei) and teleost (Teleostei) fishes

The kidneys of the rainbow trout Oncorhynchus mykiss, the channel catfish Ictalurus punctatus (both Teleostei), and the white sturgeon, Acipenser transmontanus (Chondrostei) displayed similar profiles of ascorbate distribution irrespective of the capability of synthesizing ascorbic acid. The head kidney was found to be the richest in ascorbate, whereas the trunk kidney showed significantly lower ascorbate levels in all three species. The head kidney richness in ascorbate was correlated with the localization of the cortical and chromaffin tissues known to accumulate ascorbate in some fish and mammals. Based on ascorbate concentration, it was possible to distinguish the head from the trunk kidney in salmonids and sturgeons which have an antero-posterior-fused kidney. The absence of l-gulonolactone oxidase activity in the kidneys of the channel catfish and the rainbow trout was asserted biochemically. We also confirmed that the ascorbic acid-synthesizing enzyme exists in white sturgeon kidney, and found that the enzyme distribution was inversely correlated with ascorbate concentrations. An active transport of ascorbate might exist in the head kidney of both acipenserids and the teleosts in order to maintain this vitamin at high concentrations. This report suggests a link between ascorbate concentration and its physiological functions in kidneys of lower vertebrates.Abbreviations AA ascorbic acid - TAA total ascorbic acid - DHA dehydroascorbic acid - DCIP dichloroindophenol - EDTA ethylenediaminetetra-acetic acid - GLO l-gulonolactone oxidase     

Distribution and tissue specificity of glutamate decarboxylase (EC 4.1.1.15).

Abstract— The activity of L–glutamate decarboxylase (EC 4.1.1.15) (GAD) in various mouse tissues was determined by five different methods, namely, the radiometric CO₂ method, column separation, electro–phoretic separation, the filtration method, and amino acid analysis. Results from the latter four methods agreed well, showing that brain had the highest activity, 4.27 nmol/min/mg protein (100%), followed by heart (7.4%), kidney (6.3%) and liver (1.5%). Measurement of brain GAD using the radiometric CO₂ assay method agreed with the other techniques. However, in heart, kidney, and liver, the GAD activities measured by the CO₂ method were about 3–4 times higher than those obtained by the GABA method, suggesting that the CO₂ method does not give a valid measurement of GAD activity in a crude non–neural tissue preparation. GAD activity also was detected in adrenal gland but not in pituitary, stomach, testis, muscle, uterus, lung, salivary gland, or spleen. GAD from brain, spinal cord, heart, kidney and liver were further compared by double immunodiffusion, enzyme inhibition by antibody, and microcomplement fixation using antibody against GAD purified from mouse brain. GAD from brain and spinal cord appear to be identical as judged from the following results: the immunoprecipitin bands fused together without a spur; the enzyme activity was inhibited by anti–GAD to the same extent; and the microcomplement fixation curves were similar in both the shape of the curve and the extent of fixation. No crossreactivity was observed between GAD from heart, kidney or liver and antibody against brain GAD in all the immunochemical tests described above, suggesting that GAD in non–neural tissues is different from that in brain and spinal cord.     

Tissue distribution and kininogen gene expression after acute-phase inflammation

A kinin-directed monoclonal antibody to kininogens has been developed by the fusion of murine myeloma cells with mouse splenocytes immunized with bradykinin-conjugated hemocyanin. The hybrid cells were screened by an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay (RIA) for the secretion of antibodies to bradykinin. Ascitic fluids were produced and purified by a bradykinin-agarose affinity column. The monoclonal antibody (IgG1) bound to bradykinin, Lys-bradykinin, Met-Lys-bradykinin, and kininogens in ELISA. Further, this target-directed monoclonal antibody recognized purified low and high molecular weight bovine, human, or rat kininogens and T-kininogen in Western blotting. After turpentine-induced acute inflammation, rat kininogen levels increased dramatically in liver and serum as well as in the perfused pituitary, heart, lung, kidney, thymus, and other tissues, as identified by the kinin-directed kininogen antibody in Western blot analyses. The results were confirmed by measuring kinin equivalents of kininogens with a kinin RIA. During an induced inflammatory response, rat kininogens were localized immunohistochemically with the kinin-directed monoclonal antibody in parenchymal cells of liver, in acinar cells and some granular convoluted tubules of submandibular gland, and in the collecting tubules of kidney. Northern and cytoplasmic dot blot analyses using a kinin oligonucleotide probe showed that kininogen mRNA levels in liver but not in other tissues increase after turpentine-induced inflammation. The results indicated that rat kininogens are distributed in various tissues in addition to liver and only liver kininogen is induced by acute inflammation. The target-directed kininogen monoclonal antibody is a useful reagent for studying the structure, localization, and function of kininogens or any protein molecule containing the kinin moiety.     

Antioxidative role of melatonin in organophosphate toxicity in rats

Previous studies revealed that oxidative stress could be an important component of the mechanism of organophosphate (OP) compound toxicity. The aim of the present study was to investigate both prophylactic and therapeutic effects of melatonin against fenthion-induced oxidative stress in rats. Therefore, we determined the changes in the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the whole blood, brain, pectoral muscle, liver, lung, heart, kidney, pancreas, and jejunum. Also, the changes in the levels of serum nitrite and nitrate, ascorbic acid, retinal, b-carotene, and ceruloplasmin were measured. In addition, activities of enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in erythrocyte of normal and experimental animals were measured. It was found that fenthion administration increased the levels of MDA in all tissues and decreased or increased the levels of GSH in some tissues. In comparison to nitrate, nitrite and ascorbic acid levels in the serum of experimental groups, there was no significant difference between groups. However, fenthion toxicity led to decrease in retinol and β-carotene levels; melatonin administration significantly prevented this decrease. Serum ceruloplasmin level was increased due to fenthion administration, but prophylactic and therapeutic melatonin administration inhibited the increase in ceruloplasmin level of serum. There was no significant change in SOD levels in melatonin-administered groups. Melatonin modulates the fenthion-induced changes in the activities of GPx and CAT. In conclusion, the results of the current study revealed that OP toxicity, induced by fenthion, activated oxidant systems in all antioxidant systems in some tissues. Melatonin administration led to a marked increase in antioxidant activity and inhibited lipid peroxidation in most of tissues.