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Biomedical subjects

M Athar

Publications and source records attributed to M Athar.

At least 91 records · Page 5Linked to original sources
PubMed1989

Evaluation of nickel complexes of bioligands-effect on distribution profile.

Distribution of various nickel-63 bioligand complexes in tissues of rats and their binding to subcellular fractions have been studied. Nickel-binding with glutathione and histidine significantly decreased nickel-63 accumulation while nickel-serum binding increased nickel body burden and its accumulation is subcellular fractions. Nickel-renal cytosol binding exhibited distribution pattern similar to serum complex only in lung tissue.

Animals↗
PubMed1988

In situ evidence for the involvement of superoxide anions in cutaneous porphyrin photosensitization.

Dihematoporphyrin ether, also known as Photofrin-II (Pf-II) is currently used in the diagnosis and management of a variety of epithelial neoplasms, in a modality known as photodynamic therapy (PDT). A major drawback of these porphyrins for PDT is their ability to evoke prolonged cutaneous photosensitization. The mechanism of tumor ablation and cutaneous photosensitization by these photosensitizers is thought to relate to the generation of one or more reactive oxygen species such as superoxide anion, singlet oxygen and hydroxyl radical. However, the role of these oxygen species has not been established unequivocally. In this study, the mechanism of Pf-II-mediated cutaneous photosensitization was examined using murine ear swelling as a marker. The mice treated with Pf-II and light demonstrated two-fold enhancement of ear swelling whereas animals treated with the SOD mimic, beta-carotene and dimethyl sulfoxide (DMSO) had considerably less ear swelling (p less than 0.01). The observed protective effect was dependent on the dose of each quencher and followed the pattern SOD mimic DMSO beta-carotene. The histopathologic alterations caused by Pf-II photosensitization were significantly alleviated by pretreatment with SOD mimic whereas beta-carotene and (DMSO) were less effective. Inhibitors of superoxide dismutase (sodium diethyldithiocarbamate) and catalase (hydroxyl amine and 3, amino 1,2,4-triazole) augmented Pf-II-mediated cutaneous photosensitization. These data provide the first in vivo evidence for the involvement of superoxide anion in cutaneous porphyrin photosensitization.

Animals↗
PubMed1988

Metastatic extramammary Paget's disease: dramatic response to combined modality treatment.

A case of extramammary Paget's disease is reported. The distinguishing features of the case are: (1) localization of the primary lesion to the scrotum, (2) development of metastases in the absence of a recognizable underlying carcinoma, and (3) response of the systemic disease to a combination of radiation therapy and chemotherapy. The histogenesis, clinical behavior, and treatment of extramammary Paget's disease are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Alleviation of nickel-induced biochemical alterations by chelating agents.

The effect of 1,4,8,11-tetraazacyclotetradecane (Cyclam), triethylenetetramine (TETA), reduced glutathione (GSH), ethylenediamine tetraacetic acid (EDTA), cyclohexanediamine tetraacetic acid (CDTA), diethylene triamine pentaacetic acid (DTPA), and hydroxyethylenediamine triacetic acid (HEDTA) on the alleviation of nickel-induced biochemical and trace-metal alterations in serum, liver, and kidney of nickel-treated rats was studied. The lipophilic chelating agents Cyclam and TETA exhibited a higher order of effectiveness in alleviating nickel-induced alterations compared to EDTA, CDTA, DTPA, and HEDTA, the hydrophilic chelating agents. The higher efficacy of lipophilic agents may be due to their ability to bind to nickel present in extracellular fluid as well as in intracellular fluid, while the hydrophilic agents may bind only to nickel present in extracellular fluid. Our data also suggest that the efficacy of Cyclam to ameliorate nickel-induced alterations is exceptionally high.

Alanine Transaminase↗
PubMed1988

Differential role of reactive oxygen intermediates in photofrin-I- and photofrin-II-mediated photoenhancement of lipid peroxidation in epidermal microsomal membranes.

Photoradiation therapy with porphyrins and light offers an alternative approach to the management of certain types of cancer. The mechanism of tissue destruction mediated by this modality is poorly understood. In this study, epidermal microsomes incubated in vitro with Photofrin-I (Pf-I) and Photofrin-II (Pf-II) followed by exposure to radiation (approximately 400 nm) resulted in increased (180%) NADPH-supported (enzymatic) as well as ADP/iron-supported (140%) (nonenzymatic) lipid peroxidative damage as measured by malondialdehyde formation. Lipid peroxidation by Pf-I and Pf-II was found to be differentially affected by quenchers of singlet oxygen (2,5-dimethylfuran, histidine, beta-carotene, ascorbic acid, and sodium azide), superoxide anion (superoxide dismutase), and the hydroxyl radical (sodium benzoate, mannitol, and ethanol). Catalase, a quencher of hydrogen peroxide, afforded significant protection only against Pf-II-enhanced lipid peroxidative damage while it had little effect against the Pf-I-mediated reaction. Deuterium oxide, which is known to increase the half-life of singlet oxygen, was found to enhance Pf-I-mediated lipid peroxidation but produced insignificant effects upon Pf-II-mediated photosensitization. Our results indicate that Pf-I and Pf-II, which are employed for the photodynamic therapy of malignant tumors, evoke membrane damage by generating different reactive oxygen species. The Pf-I-mediated photodestruction mainly involves a type II mechanism via singlet oxygen formation, whereas Pf-II-mediated photodestruction preferentially involves a type I mechanism by generating superoxide anions and hydroxyl radicals. Our data indicate that tumor necrosis evoked by porphyrins and light is likely due to the generation of reactive oxygen species.

Animals↗
PubMed1987

Evidence for the involvement of hydroxyl radicals in nickel mediated enhancement of lipid peroxidation: implications for nickel carcinogenesis.

The administration of nickel to rats resulted in enhanced hepatic lipid peroxidation, levels of glutathione and iron with a concomitant decrease in glutathione peroxidase activity. These effects were dose dependent. Enhanced lipid peroxidation was found to be inhibited by the exogenous addition of ethylenediamine tetraacetic acid (EDTA), benzoate and ethanol while catalase and superoxide dismutase were ineffective in this regard. Our data strongly suggest the involvement of hydroxyl radicals in the nickel mediated enhancement of lipid peroxidation which may have their implications in the carcinogenicity of nickel compounds.

Animals↗
PubMed1987

Cytochrome P-450 dependent metabolism of testosterone in rat skin.

The incubation of microsomes of whole skin, dermis and epidermis with 14C testosterone in the presence of NADPH resulted in the formation of 6 beta-, 7 alpha- and 16 alpha-testosterone. Maximum enzyme activity occurred in epidermal microsomes followed by dermis and whole skin. Epidermal testosterone hydroxylase activity required NADPH and oxygen and was found to be inhibited by SKF 525A and metyrapone. Our data strongly suggest that testosterone is metabolized by the cytochrome P-450 dependent monooxygenase in skin and provides the first evidence for an endogenous substrate for cytochrome P-450 in this tissue. The formation of several hydroxylated products further suggests the existence of multiple isozymes of cytochrome P-450 in rat skin. These studies provide additional evidence that target tissues may modulate their hormone levels by enzyme pathways that are locally regulated.

Animals↗
PubMed1987

Evaluation of chelating drugs on the toxicity, excretion, and distribution of nickel in poisoned rats.

The effects of various doses of two macrocyclic drugs, namely, 1,4,8,11-tetraazacyclotetradecane (Cyclam) and 5,7,7',12,14,14'-hexamethyl-1,4,8,11-tetraazacyclotetradecane++ + (Cyclam s), on the toxicity, distribution, and excretion of nickel were evaluated in nickel-poisoned rats and compared with the linear counterpart triethylenetetraamine (TETA) and a tripeptide, glutathione (GSH). Cyclam and Cyclam s revealed a higher order of efficacy against the lethal response of nickel even at a lower dose. These drugs significantly enhanced the urinary and biliary excretion of nickel and restored the altered levels of trace metals (viz., Cu, Zn, Fe, Mn) compared to TETA and GSH. The efficacy of these drugs in vivo may be related to their ability to transport nickel across an artificial lipid membrane, a phenomenon was not exhibited by TETA or GSH.

Animals↗
PubMed1987

Role of glutathione metabolizing enzymes in nickel mediated induction of hepatic glutathione.

The administration of nickel to rats resulted in a dose-dependent increase in the level of hepatic glutathione and in the activities of glutathione reductase and glutathione-S-transferase with a concomitant decrease in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase. The increase in hepatic glutathione may be due to the decrease in the activities of glutathione utilizing enzymes and increase in the activity of glutathione reductase leading to the increased turnover of glutathione.

Animals↗
PubMedDate not supplied

Inhibition of the skin tumorigenicity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene by tannic acid, green tea polyphenols and quercetin in Sencar mice.

The effect of pretreatment of skin of Sencar mice with topically applied tannic acid, quercetin and green tea polyphenols (GTP) on the skin tumor initiating activity of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-2) has been evaluated. The animals were pretreated with the plant phenols (tannic acid and quercetin (3000 nmol) or GTP 24 mg/mouse) for 7 days after which they received a single topical application of 200 nmol of BPDE-2 as the initiating agent. Beginning 7 days following initiation animals received twice weekly applications of 3.24 nmol of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Tannic acid and GTP afforded significant protection against skin tumor induction. These inhibitory effects were verified both by prolongation of the latency period and subsequent development of tumors. Quercetin, on the other hand, afforded only moderate protection. Each phenolic compound was found to be highly effective in accelerating the disappearance of BPDE-2 from aqueous medium. Our results suggest that tannic acid and GTP have substantial potential for protecting against the skin tumorigenic response to BPDE-2 and the mechanism of inhibition may involve inactivation of the reactive carcinogenic moiety.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMedDate not supplied

Evaluation of LD50 of some polyaminocarboxylic acids used as chelating drugs in metal intoxication.

The LD50 of the following metal-binding chelating drugs, EDTA, diethylenetriaminepentaacetic acid (DTPA), hydroxyethylenediaminetriacetic acid (HEDTA), cyclohexanediaminotetraacetic acid (CDTA) and triethylenetetraminehexaacetic acid (TTHA) was evaluated in terms of mortality in rats after intraperitoneal administration and was found to be in the order: CDTA greater than EDTA greater than DTPA greater than TTHA greater than HEDTA. A possible correlation between the toxicity and molecular structure of the compounds is discussed.

Animals↗
PubMedDate not supplied

Evidence that iron-overload promotes 7,12-dimethylbenz(a)anthracene- induced skin tumorigenesis in mice.

Iron overload is known to occur in West European and American populations due to the consumption of an iron-rich diet. There are also genetic disorders which lead to body iron overload. It has been shown that iron overload predisposes humans to an increased risk of cancer. In experimental animals, iron overload is known to enhance intestinal, colon, hepatic, pulmonary and mammary carcinogenesis. However, the mechanism by which iron overload enhances chemically-induced carcinogenesis is not known. In this study, we show that iron overload acts as a mild tumor promoter in mouse skin. Female albino swiss mice were given 1 mg iron/mouse parenterally for 2 weeks to induce iron overload. These animals showed a three-fold increase in cutaneous iron concentration as compared to normal mice. Tumors were initiated by topically applying 7,12-dimethylbenz(a)anthracene (DMBA). Appearance of the first tumor (latency period), percent tumor incidence and number of tumors/mouse were recorded. When compared to the control group, iron overload mice showed an increased incidence of tumors, from 25%-55% by week 20, and tumors appeared 4 weeks earlier. The number of tumors per mouse was four-fold higher in the iron overload group. The induction of cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA were higher in iron overload groups as compared to normal control animals. Similar to other oxidant tumor promoters, iron overload enhanced cutaneous lipid peroxidation and xanthine oxidase activity and decreased catalase activity. Our results indicate that iron overload exerts a mild tumor promoting activity in mouse skin. Our data also show that oxidative stress generated by iron overload plays an important role in the augmentation of cutaneous tumorigenesis. These data may also have implications for the enhanced risk of cancer-induction following UVB exposure of human populations with iron overload.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Iron overload augments 7,12-dimethylbenz(a)anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumorigenesis.

Reactive oxygen species and free radicals have been implicated in the multistep cutaneous chemical carcinogenesis. Much of the experimental evidence in this regard is indirect and is based on observations that prooxidant status usually enhances and antioxidant treatments generally inhibit tumor yield. Iron overload is known to enhance peroxidative damage and cause oxidative stress. In this study, we report that iron overload augments 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated cutaneous tumor promotion. Female Swiss mice were subjected to iron overload by injecting 1 mg iron/ mouse/day consecutively for 2 weeks. Tumors were initiated by applying a single dose of 7,12-dimethylbenz(a)anthracene and promoted with twice weekly applications of TPA for 20 weeks and the appearance of first tumor (latency period), percent incidence and number of tumors per mouse were recorded. It has been observed that the level of iron in involved (tumor-bearing) skin was about fourfold higher as compared to uninvolved (non-tumor) skin of iron overload animals and about tenfold higher as compared to the iron level in the skin of normal animals. When compared to the iron-unloaded control group, the iron overload mice showed an increased incidence of tumors. In iron overload animals, the tumors appeared 3 weeks earlier and also the number of tumors per mouse was significantly higher (2.5-fold). These data indicate that iron overload augments TPA-mediated tumor promotion. We propose that oxidative stress generated by iron overload may be responsible for the augmentation of cutaneous tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Chemoprevention of basal cell carcinomas in the ptc1+/- mouse--green and black tea.

Skin cancers are a rising menace as their incidence increases, attributed in part to increasing ultraviolet radiation exposure. This increasing problem has stimulated efforts to devise useful preventive approaches. The uncertain efficacy of exhortations to avoid sun exposure and to use protective clothing and sunscreens to reduce damage when exposed argue for the development of an oral chemopreventive agent. Bickers and others have studied the effects and mechanisms of tea and of its putative active components on inhibition of skin cancer in experimental models. To continue this work, we have studied the effects of oral green tea and black tea on a new model of ultraviolet-induced skin carcinogenesis - the development of basal cell carcinomas in ptc1+/- mice. To our surprise, we have found that tea preparations which others have used to prevent squamous cell carcinoma formation in mice fail to inhibit basal cell carcinogenesis in our model, suggesting that prevention of this cancer may require special, tumor-specific approaches.

Alleles↗