Several Organs Of Rats Research Articles

Cathine and cathinone disposition kinetics and neurotransmitter profile in several organs of rats exposed to a single dose of Catha edulis (Vahl) Forssk. ex Endl. extract.

Catha edulis (Vahl) Forssk. ex Endl. (Khat) is a stimulant plant that contains cathine and cathinone, which its abuses induce euphoria, alertness, and motor activity. Since the toxicokinetics of these substances remain unclear, this study was carried out to investigate the disposition kinetics of cathine and cathinone, the neurotransmitter profile, following a single dose of C.edulis extract in rats. Twenty-four adult male Wistar albino rats (250-300g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method. The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5h. The concentrations peaked in the brain 2.5h later, indicating thatthe heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68and5.07h, respectively) and may remain in the brain for longer durations (3.31 and 2.31h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner. Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest Cmax in the lung and Tmax in the heart tissues but notin the brain. In addition, neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin were differentially detected in all tested samples in a organ-specific fashion. More study is needed to identify cathine andcathinone's effects on neurotransmitter profiles. Nevertheless, these findings provided a further basis for experimental, clinical, and forensic investigations.

Dietary restriction modulates mitochondrial DNA damage and oxylipin profile in aged rats.

Age-related impairment of coordination of the processes of maintaining mitochondrial homeostasis is associated with a decrease in the functionality of cells and leads to degenerative processes. mtDNA can be a marker of oxidative stress and tissue degeneration. However, the mechanism of accumulation of age-related damage in mtDNA remains unclear. In the present study, we analyzed the accumulation of mtDNA damage in several organs of rats during aging and the possibility of reversing these alterations by dietary restriction (DR). We showed that mtDNA of brain compartments (with the exception of the cerebellum), along with kidney mtDNA, was the most susceptible to accumulation of age-related damage, whereas liver, testis, and lung were the least susceptible organs. DR prevented age-related accumulation of mtDNA damage in the cortex and led to its decrease in the lung and testis. Changes in mtDNA copy number and expression of genes involved in the regulation of mitochondrial biogenesis and mitophagy were also tissue-specific. There was a tendency for an age-related decrease in the copy number of mtDNA in the striatum and its increase in the kidney. DR promoted an increase in the amount of mtDNA in the cerebellum and hippocampus. mtDNA damage may be associated not only with the metabolic activity of organs, but also with the lipid composition and activity of processes associated with the isoprostanes pathway of lipid peroxidation. The comparison of polyunsaturated fatty acids and oxylipin profiles in old rats showed that DR decreased the synthesis of arachidonic acid and its metabolites synthesized by the cyclooxygenase, cytochrome P450 monooxygenases and lipoxygenase metabolic pathways.

1,4-dihydropyridine derivatives increase mRNA expression of Psma3, Psmb5, and Psmc6 in rats.

The ubiquitin-proteasome system modifies different cellular and protein functions. Its dysregulation may lead to disrupted proteostasis associated with multiple pathologies and aging. Pharmacological regulation of proteasome functions is already an important part of the treatment of several diseases. 1,4-dihydropyridine (1,4-DHP) derivatives possess different pharmacological activities, including antiaging and neuroprotective. The aim of this study was to investigate the effects of several 1,4-DHP derivatives on mRNA expression levels of proteasomal genes Psma3, Psmb5, and Psmc6 in several organs of rats. Rats were treated with metcarbatone, etcarbatone, glutapyrone, styrylcarbatone, AV-153-Na, or AV-153-Ca per os for three days. mRNA expression levels were determined with real-time polymerase chain reaction (PCR). For AV-153-Na and AV-153-Ca, we also determined the expression of the Psma6 gene. In the kidney, metcarbatone, etcarbatone, styrylcarbatone, and AV-153-Na increased the expression of all analysed genes. Glutapyrone increased the expression of Psmb5 and Psmc6 but did not affect the expression of Psma3. In the blood, glutapyrone increased Psmb5 expression. In the liver, AV-153-Na increased the expression of Psma6 and Psmc6 but lowered the expression of Psmb5, while AV-153-Ca only increased Psma6 expression. The ability of 1,4-DHP derivatives to increase the expression of proteasome subunit genes might hold a therapeutic potential in conditions associated with impaired proteasomal functions, but further research is needed.

Formation, Persistence, and Identification of DNA Adducts Formed by the Carcinogenic Environmental Pollutant o-Anisidine in Rats

2-Methoxyaniline (o-anisidine) is an industrial and environmental pollutant causing tumors of urinary bladder in rodents. Here, we investigated the formation and persistence of DNA adducts in the Wistar rat. Using the (32)P-postlabeling method, three o-anisidine-derived DNA adducts were found in several organs of rats treated with a total dose of 0.53 mg o-anisidine/kg body wt (0.15, 0.18, and 0.2 mg/kg body wt ip in the first, second, and third day, respectively), of which the urinary bladder had the highest levels. At four posttreatment times (1 day, 13 days, 10 weeks, and 36 weeks), DNA adducts in bladder, liver, kidney, and spleen of rats were analyzed to study their persistence. In all time points, the highest total adduct levels were found in urinary bladder (39 adducts per 10(7) nucleotides after 1 day and 15 adducts per 10(7) nucleotides after 36 weeks) where 39% adducts remained. In contrast to the urinary bladder, no persistence was detected in other organs. All three DNA adducts were identified as deoxyguanosine adducts. When deoxyguanosine was reacted with the oxidative metabolite of o-anisidine, N-(2-methoxyphenyl)hydroxylamine, three adducts could be separated by high-performance liquid chromatography (HPLC) and were identified by mass spectroscopy and/or nuclear magnetic resonance spectrometry. All adducts are products of the nitrenium/carbenium ions, the reactive species generated from N-(2-methoxyphenyl)hydroxylamine. The major adduct was identified to be N-(deoxyguanosin-8-yl)-2-methoxyaniline. Using cochromatography on HPLC, this adduct was found to be identical to the major adduct generated by activation of o-anisidine in vitro and in vivo.

The Influence of Size and Exposure Duration of Gold Nanoparticles on Gold Nanoparticles Levels in Several Rat Organs In vivo

Background: The bioaccumulation and toxicity of Gold Nanoparticles (GNPs) in several organs of rats becomes of more necessity prior to using them in drug delivery, diagnostics, and treatment. The GNPs levels in several rat organs in vivo have not been previously documented. This study was aimed to evaluate the influence of size and exposure duration of GNPs on the GNPs levels in several organs of rats in vivo. Methods: Thirty rats were divided into a control group (NG: n = 10), group 1 (G1A: infusion of 10 nm GNPs for 3 days; n = 5; G1B: 10 nm GNPs for 7 days; n = 5) and group 2 (G2A: 50 nm GNPs for 3 days; n = 5; G2B: 50 nm GNPs for 7 days; n = 5). 50 μl of GNPs dissolved in aqueous solution were administered intraperitoneally every day for 3 and 7 days. Results: The GNPs levels were evaluated in several rat organs by Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) and Atomic Absorption Spectroscopy (AAS). In comparison with the control group, the GNPs levels increased in all the examined organs with G1A, G1B, G2A and G2B. The highest percentage normalized increase in the liver and lung organs were 468.6% and 273.4%, respectively with 10 nm GNPs after administration period of 7 days. The highest percentage normalized increase in the kidney and heart organs were 258.7% and 242.6%, respectively with 10 nm GNPs for administration period of 3 days. Conclusions: Our results might indicate that GNPs are mostly taken up and accumulate in organs, suggesting the toxic effects induced by the smaller GNPs. These conclusions are further supported by histological investigation suggesting that the highest toxic effects were induced by the smaller GNPs and related to the time exposure of GNPs.

Biodistribution of the radiopharmaceutical sodium pertechnetate after biliopancreatic bypass with a duodenal switch

Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle.

Altered fatty acid pattern of phospholipids and triglycerides in the submandibular gland of ω3‐depleted rats

Alteration of the phospholipid (PL) and triglyceride (TG) fatty acid pattern was recently documented in several organs of rats depleted in long-chain polyunsaturated omega3 fatty acid (omega3 rats). This study extends such a knowledge to the submandibular gland. The total PL and TG content of the salivary gland was not different in control and omega3 rats. The sole omega3 fatty acids found in omega3 rats (C22:5omega3 and C22:6omega3) were present at levels 3-12 times lower than in control rats. The C22:5omega3/C22:6omega3 ratio was increased threefold in omega3 rats. The PL and TG C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios were decreased in omega3 rats. The conversion of C18:2omega6 to C20:4omega6 and C22:4omega6 appeared facilitated in the omega3 rats. Some of these rats were injected intravenously, 60-120 min before killing, with either a medium-chain triglyceride:fish oil emulsion or a control medium-chain triglyceride:olive oil emulsion. The former emulsion increased the PL C22:5omega3 and C22:6omega3 content and prevented the age-related decrease in C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios otherwise also recorded in PL. In conclusion, these findings document an increased activity of Delta9-desaturase, a more efficient conversion of C18:2omega6 to its metabolites, and an impaired generation of C22:6omega3 from C22:5omega3 in omega3 rats.

Depletion and recovery of catecholamines in several organs of rats treated with reserpine

Chemical sympathectomy with reserpine depletes catecholamines in every neuronal or nonneuronal cell producing a nonspecific temporal sympathectomy. After reserpine administration, most of the drug is distributed to tissues based on their blood flow and would then either be metabolized or be reversibly bound in lipid depots from where it might be released. Consequently, reserpine concentration and the catecholamine-depleting effect in the various tissues are expected to differ according to the route of administration. This study was designed to compare the effects of intraperitoneal (i.p.) and subcutaneous (s.c.) administration of reserpine on catecholamine depletion and recovery in the liver, portal vein, and adrenal gland on days 1, 4, and 10 after reserpine dosage. Catecholamine determinations were extended to 25 days after the treatment only in s.c. reserpine-treated rats and adding samples of heart and brown adipose tissue to the testing. I.p. and s.c. reserpine administration had the same norepinephrine-depleting effect in the portal vein and liver but full recovery was present in both tissues only in i.p. reserpine-treated rats. In the adrenal gland, both routes of administration produced the same depleting and recovery effect of norepinephrine and epinephrine concentrations. A significant temporary overshoot in epinephrine levels was observed several days after s.c. reserpine treatment. Except for the liver, reserpine injected s.c. depleted norepinephrine concentrations significantly in all other tissues up to the end of the experiment. Our results suggest that chemical sympathectomy caused by reserpine administered s.c. produces a generalized and prolonged decrease in peripheral sympathetic activity that could be compensated by an increase in activity of the adrenal gland.

Syntheses of DNA adducts of two heterocyclic amines, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-9H-pyrido[2,3-b]indole (AalphaC) and identification of DNA adducts in organs from rats dosed with MeAalphaC.

2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeAalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b]indole (AalphaC) are mutagenic and carcinogenic heterocyclic amines formed during ordinary cooking. MeAalphaC and AalphaC are activated to mutagenic metabolites by cytochrome P450-mediated N-oxidation to the corresponding N2-OH derivatives. The proximate mutagenic N2-OH derivatives of MeAalphaC and AalphaC did not react with deoxynucleosides or DNA. However, upon acetylation with acetic anhydride both reacted with 2'-deoxyguannosine and 3'-phospho-2'-deoxyguanosine, resulting in one adduct each, but not with other nucleosides or nucleotides. The adducts were identified as N2-(2'-deoxyguanosin-8-yl)-MeAalphaC, N2-(2'-deoxyguanosin-8-yl)-AalphaC, N2-(3'-phospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3'-phospho-2'-deoxyguanosin-8-yl)-AalphaC by comparison with adducts of known structure obtained by reaction of the parent amines with acetylated guanine N3-oxide. N2-OH-MeAalphaC and N2-OH-AalphaC reacted with calf thymus DNA after addition of acetic anhydride. 32P-postlabelling analysis of modified DNA showed one major adduct co-migrating with N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-MeAalphaC and N2-(3',5'-diphospho-2'-deoxyguanosin-8-yl)-AalphaC, respectively. Some minor adducts presumed to be undigested oligomers were also detected. 32P-postlabelling analysis of DNA from several organs of rats dosed orally with MeAalphaC showed that in vivo N2-(2'-deoxyguanosin-8-yl)-MeAalphaC also was the major adduct formed. Relative adduct level in DNA isolated from the liver of the rats was about 50.40 adducts/10(9) nt. The adduct levels were approximately 4-fold lower in the colon and the heart and approximately 12-fold lower in the kidney of the rats.

Does corticosteroid metabolism in target organs affect the cardiovascular system?

The target organ metabolism of corticosteroids has been measured with biochemical and immunohistochernical techniques. Attention was focused on the key enzyme system 11β-hydroxysteroid oxidoreductase (11β-HSOR, EC 1.1.1.146). Several organs of rats, including kidney, colon, testis, pancreas, liver, lung and heart, express oxidative, as well as reductive activity, albeit with different ratios. The specific co-substrate preference in different organs points to the presence of isoforms of the enzyme, which can be inhibited by steroid compounds. In kidney tubules longitudinal heterogeneity of the enzyme distribution pattern has been reported. Inhibition of 11β-HSOR in transporting epithelia such as those of kidney and colon by liquorice, glycytrhetinic acid and others leads to aldosterone-like effects of glucocorticosteroids. The mechanism of this effect is breakdown of the specific 11β-HSOR barrier for glucocorticosteroids which subsequently bind to mineralocorticosteroid receptors. Other possible mechanisms of interaction of the corticosteroid metabolism and the cardiovascular system are discussed.

5-Azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis

It is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylaion. The known data on its clastogenic and/or gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endpoints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell trnsformation) were assayed under similar conditions of metabolism and dose at target in this cell system, 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of micronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.

ラットアポA-IVの免疫組織学的検討

The localization of apo A-IV was examined in several organs of rats using an immunohistochemical technique. It is well known that rat apo A-IV is synthesized in the small intestine and in the liver. However, the catabolic site of apo A-IV has not been fully understood. In the present study, apo A-IV was positive in the epithelium of the small intestine, liver cells, and renal proximal tubular cells, and was negative in the large intestine. Apo A-IV was localized in villus epithelium both in the jejunum and ileum, and the intensity of staining for apo A-IV was greater in jejunum than ileum. The stained liver cells were scattered around the central vein. The positive findings both in the small intestine and the liver are compatible with the fact that these organs are responsible for the synthesis of apo A-IV. On the other hand, apo A-IV was also detected in renal proximal tubular cells when glomerulus was not stained.Since it is considered that apo A-IV is not synthesized in the kidney, it is feasible that apo A-IV in the plasma passes through the glomerulus, and is then taken up by tubular cells as well as other lowmolecular-weight proteins.

DNA repair mechanisms and their biologic implications in mammalian cells: Report of a NATO advanced research workshop, Fontevraud, France, Oct. 2–7, 1988

Repair of Alkylation Damage in DNA.- Structure-Function Relationships in Alkylation Damage and Repair.- The Roles of Beta- and Delta-Elimination in the Repair of AP Sites in DNA.- Imidazole Ring-Opened Purines: Occurence and Repair in Escherichia coli and Mammalian Cells.- Substrate Specificity of the Formamidopyrimidine-DNA Glycosylase of E. coli: Repair of the Imidazole Ring-Opened Form of N-Hydroxy-2-Amino-Fluorene-Guanine Adducts in DNA.- Investigation of Sequence Specificity in DNA Alkylation and Repair Using Oligodeoxynucleotide Substrates.- Towards a Role for Promutagenic Lesions in Carcinogenesis.- Acquisition of Resistance to Alkylating Agents by Expression of Methyltransferase Gene in Repair-Deficient Human Cells.- The Mer Minus Phenotype, Patient Response to Nitrosoureas, and Protooncogene Activation in Human Glioblastomas.- The Molecular Basis of Alkylating Agent Resistance in Mammalian Cells.- Differential Repair of O4-Methylthymine and O6-Methylguanine in Rat and Hamster Liver.- Formation of 1, N6-Ethenodeoxyadenosine and 3, N4-Ethenodeoxycytidine in DNA from Several Organs of Rats Exposed to Vinyl Chloride.- The Role of O6-Alkylguanine in Cell Killing and Sister Chromatid Exchange Induced by Alkylating Agents.- Inducible Responses to DNA Damage.- Inducible Repair in Mammalian Cells Treated with Alkylating Agents.- An Update of the Mammalian UV Response: Gene Regulation and Induction of a Protective Function.- DNA Repair Related Events.- The Transportation of AP Endonuclease from Cytoplasm to Nucleus in Mammalian Cells.- DNA Damage and Oxygen Species.- Mutagenesis.- Molecular Studies of Mutagenesis using Plasmid Vectors in Xeroderma Pigmentosum Cells.- Molecular Analysis of Mutations at the HPRT Locus: UV Mutation Spectra in Normal and UV-Sensitive V79 Chinese Hamster Cells.- Comparison of the Mutational Specificities Exhibited by BPDE in Escherichia coli and CHO Cells.- Deoxyribonucleotide Pools, DNA Repair and Mutagenesis.- Recombination and Mismatch Repair.- Duplex-Duplex Homologous Recombination Catalysed by a Human Nuclear Extract. Involvement in Double-Strand Break Repair.- Proteins from Yeast and Human Cells Specific for Model Holliday Junctions in DNA.- Characterization of a Strand Transferase Activity from Human Cells.- Mismatch Repair in Mammalian Cells: Approaches to the In Vitro Study of DNA Mismatch Correction Reactions.- Mismatch Repair Patterns in Simian Cells Correlate with the Specificity of a Mismatch Binding Protein Isolated from Simian and HeLa Cells.- Chromatin Proteins and Chromatin Structure in DNA Repair.- DNA Excision Repair at the Nucleosome Level of Chromatin.- Modulation of Activity of Human Chromatin-Associated Endonucleases on Damaged DNA by Nucleosome Structure.- Relationship Between DNA Repair and Transcription in Defined DNA Sequences in Mammalian Cells.- Non-Random Distribution of UV-Induced Repair in Higher-Order Chromatin Loops in Human Cells and its Relationship to Preferential Repair of Active Genes.- Electron Microscopic Visualization of Chromatin Structure at Sites of DNA Excision Repair Following Ultraviolet Irradiation of Cultured Human Fibroblasts.- Poly(ADP-Ribosyl)ation Reactions and Modulation of Chromatin Structure.- Variation of Nuclear ADP-Ribosyl Transferase in Rat Liver Carcinogenesis and in Synchronized HeLa Cells.- DNA Repair Processes in Mutant Cells Deficient in Poly(ADP-Ribose) Synthesis.- Repair Defective Cell Types.- Co-Recessive Inheritance: A Model for Diseases Associated with Defective DNA Repair.- Mammalian DNA Ligases and the Molecular Defect in Bloom's Syndrome.- Detection of Unique Antigenic Lesions in the Uracil DNA Glycosylase from Bloom's Syndrome.- DNA Ligase Activity in Human Cells from Normal Donors and from Patients with Bloom's Syndrome and Fanconi's Anemia.- Processing of Photoinduced Cross-Links and Monoadducts in Human Cell DNA: Genetic and Molecular Features.- Parallels Between Nucleotide Excision Repair in Human Cells and E. coli.- Mechanisms of Resistance to Ionising Radiations: Genetic and Molecular Studies on Ataxia-Telangiectasia and Related Radiation-Sensitive Mutants.- Defective DNA Synthesis and/or Repair in Amyotrophic Lateral Sclerosis.- Genetic Analysis in Trichothiodystrophy Repair Deficient Cells Confirms the Occurrence of Xeroderma Pigmentosum Group D Mutation in Unrelated Patients.- Chinese Hamster Cell Lines Defective in DNA Repair.- DNA Repair Genes and Oncogenes in DNA Repair.- Human DNA Repair and Recombination Genes.- Molecular Genetic Dissection of Mammalian Excision Repair.- The Cloning and Characterization of a Candidate Gene for the Correction of the Xeroderma D Defect.- Characterization of Chinese Hamster Ovary Cell Mutants Hypersensitive to DNA Damaging Agents.- Oncogene Activation in Xeroderma Pigmentosum Skin Tumors.- Anticancer Drugs in DNA Repair.- Heterogeneity in the O6-Alkylguanine DNA Alkyl-Transferase (AGT) Activity of Human Peripheral Blood Lymphocytes (PBL's).- Formation and Repair of Adducts that Lead to Cross-Links in DNA Treated with Chloro-Ethylating Agents.- Induction of Futile DNA Repair Processing by Bifunctional Intercalators.- Participants.- Author Index.

Mucopolysaccharidosis-like cellular alterations in chondrocytes of rats treated with tilorone

The dicationic amphiphilic compound tilorone was previously shown to interfere with the lysosomal degradation of sulfated glycosaminoglycans (GAGs) of cultured cells and to cause mucopolysaccharidosis-like alterations in several organs of rats. Since chondrocytes belong to those cells that are severely affected in cases of inherited mucopolysaccharidoses, we wished to know whether this also holds true of the experimentally induced mucopolysaccharidosis. Young rats were treated with tilorone (50–80 mg/kg of body weight) for 2–17 weeks; chondrocytes in tracheal and costal cartilage and in the epiphyseal growth plates of the tibia and ribs were examined by electron microscopy and cytochemistry (acid trimetaphosphatase and staining with Cuprolinic Blue). The tracheal and costal chondrocytes showed numerous abnormal clear vacuoles. Some of them could be identified cytochemically as lysosomes filled with polyanionic storage material, probably sulfated GAGs. In the epiphyseal plate, only the resting chondrocytes were markedly affected, whereas those of the remaining zones were hardly altered; this may be due to the short life span of these chondrocytes in rat growth plates. The present results show that chondrocytes participate in the experimental mucopolysaccharidosis and suggest that, under normal conditions, the lysosomes of chondrocytes have to cope with a considerable load of GAGs.

Effect of dietary lipid peroxides on lymphoid tissues.

Several studies have been reported of the toxicity and nutritional problems associated with lipid peroxides produced during the autoxidation of oils. Lipid hydroperoxides, the primary oxidation products, and other oxidation products such as ketones, epoxides and aldehydes are thought to be the substances most responsible for the toxicity. (1) However, it has not been shown whether dietary peroxides affect the functions of immunocompetent cells or not. We have reported that methyl U-14C linoleate hydroperoxide and their radioactive secondary oxidation products (carbonyls such as 9-oxo nonanoate and 4-hydroxy nonenal) were absorbed and incorporated into several organs of rats after the oral administration. (2) To appreciate why oxidized oils that occur in foods show lesser nutritional value or toxicity, it seems important to study the effects of dietary peroxides on lymphoid tissues. We studied on the effects on lymphoid tissues of the thymus of mice induced by orally administered methyl linoleate hydroperoxide (MLHPO).

Effects of clofibric acid and tiadenol on cytosolic long-chain acyl-CoA hydrolase and peroxisomal β-oxidation in liver and extrahepatic tissues of rats

The effects of two peroxisome proliferators, p-chlorophenoxyisobutyric acid ( clofibric acid) and 2,2'-( decamethylenedithio) diethanol ( tiadenol), on cytosolic long-chain acyl-CoA hydrolase and peroxisomal β-oxidation were studied in several organs of rat. Among organs of control rats, the brain had the highest activity of long-chain acyl-CoA hydrolase, followed by testis, and a low activity was found in other tissues. Administration of the peroxisome proliferators caused a marked increase in activity of long-chain acyl-CoA hydrolase in both liver and intestinal mucosa and a slight increase in the activity in kidney, but little affected acyl-CoA hydrolase activity in either brain, testis, heart, spleen and skeletal muscle. In accordance with the change in the activity of acyl-CoA hydrolase, the activity of peroxisomal β-oxidation was markedly increased in liver, intestinal mucosa and kidney, and a slight increase was found in brain and testis, whereas peroxisome proliferators little affected the activity in other organs tested. Gel filtration of cytosol from intestinal mucosa showed that clofibric acid caused an appearance of a new peak in intestinal mucosa. Although cytosol of liver, intestinal mucosa, brain and testis contained two 4-nitrophenyl acetate esterases with different molecular weights (about 105000 and about 55000), these esterases are different from cytosolic long-chain acyl-CoA hydrolases of these four organs in respect of molecular weight. The administration of clofibric acid little affected cytosolic 4-nitrophenyl acetate esterases. Comparative studies on cytosolic long-chain acyl-CoA hydrolases from these four organs showed that liver hydrolase I (molecular weight of about 80000) had properties similar to those of brain and testis enzymes. On the other hand, intestinal mucosa enzyme was different from either hepatic hydrolase I or II (molecular weight of about 40000). The results from the present study suggest that inductions of peroxisomal β-oxidation and cytosolic long-chain acyl-CoA hydrolases are essential responses of rats to peroxisome proliferators not only in liver but also in intestinal mucosa and that induced hydrolases are not attributable to non-specific esterases.

Changes in MAO activities in several organs of rats after administration of l-thyroxine.

Male rats were given daily injections of 200 micrograms/kg l-thyroxine, s.c., for a period of 10 days. Monoamine oxidase (MAO) activities in the heart, lung and liver mitochondria decreased rapidly to about 50% those of the control rats with 5-HT and beta-phenylethylamine (beta-PEA) as substrates on the first day. After that, heart MAO activity increased gradually and exceeded the control value after 10 days with 5-HT as the substrate. The level of liver MAO activity was maintained at about 50-70% during the same period of administration with 5-HT as the substrate. The thyroxine treated rats showed no marked change in brain MAO activity. In vitro, l-thyroxine and its metabolites had no discriminative actions on MAO activities in these organs of rats. The heart, lung and liver MAO have unaltered Km values for 5-HT and beta-PEA, but decreases in the Vmax for both substrates were observed between the control and l-thyroxine-treated rats. Addition of the brain, heart and liver cytosol fractions from l-thyroxine treated rats caused MAO activities of heart mitochondria to decrease with 5-HT as a substrate and caused them to increase with beta-PEA as a substrate. MAO activities in liver also were inhibited by adding all the cytosols when beta-PEA was the substrate, but on the contrary, lung MAO activities were increased when 5-HT was the substrate. These results indicate the possible presence of multiple modulators of MAO in the cytosol fractions of l-thyroxine treated rats.

Changes in MAO Activities in Several Organs of Rats after Administration of /-Thyroxine

Male rats were given daily injections of 200 μg/kg /-thyroxine, s.c. for a period of 10 days. Monoamine oxidase (MAO) activities in the heart, lung and liver mitochondria decreased rapidly to about 50% those of the control rats with 5-HT and β-phenylethylamine (β-PEA) as substrates on the first day. After that, heart MAO activity increased gradually and exceeded the control value after 10 days with 5-HT as the substrate. The level of liver MAO activity was maintained at about 50-70% during the same period of administration with 5-HT as the substrate. The thyroxine treated rats showed no marked change in brain MAO activity. In vitro, /-thyroxine and its metabolites had no discriminative actions on MAO activities in these organs of rats. The heart, lung and liver MAO have unaltered Km values for 5-HT and β-PEA but decreases in the Vmax for both substrates were observed between the control and /-thyroxine-treated rats. Addition of the-brain, heart and liver cytosol fractions from /-thyroxine treated rats caused MAO activities of heart mitochondria to decrease with 5-HT as a substrate and caused them to increase with β-PEA as a substrate. MAO activities in liver also were inhibited by adding all the cytosols when β-PEA was the substrate, but on the contrary, lung MAO activities were increased when 5-HT was the substrate. These results indicate the possible presence of multiple modulators of MAO in the cytosol fractions of /-thyroxine treated rats.

Decrease in adrenaline content of various organs of the rat after 6-hydroxydopamine

To examine the location of adrenaline in peripheral organs of mammals, adrenaline and noradrenaline were measured in several organs of rats treated with 6-hydroxydopamine (6-OHDA) or vehicle. After the administration of 6-OHDA, there was a marked decrease in the content of both adrenaline and noradrenaline in the heart, spleen, submaxillary gland of the rat. This finding suggests that in rats adrenaline is present in noradrenaline neurons in these organs.

O-55) - Changes in MAO activities in several organs of rats after administration of ℓ-thyroxine

O-55) - Changes in MAO activities in several organs of rats after administration of ℓ-thyroxine