Quercetin attenuates di-(2-ethylhexyl) phthalate-induced testicular toxicity in adult rats.

The aim of the present study was to investigate the potential oxidative damage of di-(2-ethylhexyl) phthalate (DEHP) in the rat testis and to further elucidate the potential modulatory effect of quercetin. DEHP was diluted in corn oil and given to rats by oral gavage at doses 0, 300, 600, and 900 mg/kg/day (groups I, III, IV, or V, respectively) for 15 consecutive days. Group VI was pretreated with quercetin (90 mg/kg), 24 h before starting the experiment and then treated with DEHP (900 mg/kg/day) for 15 consecutive days. Group II was treated with quercetin (90 mg/kg/day). The relative testes weight and sperm motility were significantly decreased by treatment with 900 mg/kg of DEHP. Both sperm count and daily sperm production were significantly decreased by DEHP treatment at doses of 600 and 900 mg/kg. Serum testosterone level and prostatic acid phosphatase (ACP) activity and testicular lactate dehydrogenase-X (LDH-X) activity were significantly decreased in animals treated with 900 mg/kg. Serum total ACP activity was significantly increased in animals treated with 600 and 900 mg/kg of DEHP. DEHP treatment induced oxidative stress and histopathological abnormality. These abnormalities were effectively normalized by pretreatment with quercetin except for LDH-X near normalcy. In conclusion, the findings of this study demonstrate that DEHP impairs testicular function at least, in part, by inducing oxidative stress and quercetin has a potent protective effect against DEHP-induced testicular toxicity in rats.

Pulmonary toxicity of acrylonitrile: covalent interaction and effect on replicative and unscheduled DNA synthesis in the lung.

Acrylonitrile (VCN)-induced lung toxicity was studied following a single oral dose (46.5 mg/kg). The mechanism of toxic injury was investigated by assessing the covalent interaction of [2,3-14C]VCN with pulmonary DNA. The effect of the same dose on replicative DNA synthesis and repair in the lungs of treated rats was also investigated. Histologic examination revealed that lungs of VCN-treated animals showed moderate to marked hyperplasia of the Clara cells lining the bronchioles. [14C]Lung tissue uptake was extremely fast, having a maximum at 0.5 h after treatment (150 DPM tissue). Radioactivity in lung tissue declined gradually as a function of time, but was still detected at 72 h after treatment (59 DPM/mg tissue). Covalent binding of [14C]VCN-derived radioactivity to pulmonary DNA was time-dependent, reaching a maximum at 12 h following treatment (61 DPM/mg DNA) and was still detected at 72 h (27 DPM/mg DNA) indicating the incomplete removal of radioactivity covalently bound to DNA. Replicative DNA synthesis in lung tissue was significantly decreased at all time points studied (59, 55 and 72% of control at 0.5, 6 and 24 h, respectively). The DNA repair in the lung was increased by 2-fold at 0.5 h and 1.6-fold at 6 h following VCN oral treatment. The histologic and biochemical results presented in this study provide evidence for the acute genetic toxicity of VCN (and/or its metabolites) in lung tissue following a single oral dose of VCN.

Cutaneous bilharzial granulomas: a histopathologic study.

Histopathological studies were done on seven cutaneous lesions; all but two were clinically diagnosed as cutaneous bilharzial granulomas. Epidermal, dermal, vascular, sweat and sebaceous gland changes were demonstrated. The purpose of this paper is to present the pathogenesis of these granulomas.

Familial Behcet's syndrome.

Behcet's syndrome is reported in two families (one English and the other Egyptian). A mother and two of her sons of the English family and two brothers of the Egyptian family are described. The contradictory opinions concerning the incidence of the familial occurrence of this syndrome are partly due to uncertainty about the nosologic relationship of recurrent aphthal and Behcet's syndrome. The question of whether this syndrome should be included in a large group of aphthoses or be regarded as a true clinical entity is discussed.

Dystrophia unguis mediana canaliformis.

Three cases of dystrophia unguis mediana canaliformis are presented herein. The presence of verruca vulgaris at the base of the dystrophic canal could be the cause of such dystrophy. The course of dystrophia unguis mediana canaliformis varied. The effect of treatment in such dystrophy remains questionable.

Evaluation of interfacial bond strengths between amalgam and composite inlay.

PURPOSE: To evaluate the interfacial bond strengths between two amalgam alloys and an inlay resin composite bonded with two different luting agents. MATERIALS AND METHODS: Inlay composites (EOS) were bonded with two different bonding systems (Geristore, All-Bond 2) to high- or low-copper amalgams (Valiant, Agestan). All tested specimens were thermocycled (100 cycles), tested for tensile bond strength and compared by ANOVA (P < 0.05). RESULTS: Bond strengths varied from 5.3 to 11.4 MPa, with Geristore bonded to high-copper amalgam providing the highest strength.

Clinical evaluation of repairing old amalgam restorations with composite inlays.

PURPOSE: Clinical evaluation of repairing old amalgam restorations using composite inlays cemented with two different bonding agents. MATERIALS AND METHODS: Occluso-proximal Class II inlay cavities were prepared in 50 old defective amalgam restorations. Extra oral system (EOS) composite inlays were cemented with two different bonding agents (All-Bond 2 or Geristore). After final finishing and polishing of each restoration, evaluation was carried out at baseline, 6 months, 12 months, and 24 months using US Public Health Service criteria. The data were collected and statistically analyzed using Chi-square test. RESULTS: No significant difference was found between the two bonding materials at any time interval.

In-vitro testicular bioactivation of acrylonitrile.

The present work examines the mechanism of testicular toxicity of acrylonitrile. In testicular centrifugal fractions from Sprague Dawley rats, the metabolism of VCN to cyanide (CN-) was highest in the microsomal fraction and required NADPH for maximum activity. This biotransformation of VCN to CN- was characterized with respect to time (30 min), microsomal protein concentration (1.5 mg ml(-1)), pH (7.5) and temperature (37 degrees C). The V(max) of the reaction was 65.1 pmol CN- mg protein(-1) min(-1) and K(m) was 88.6 micromol VCN. Flushing the microsomes with carbon monoxide (CO)(4:1, CO/O2 v/v), addition of benzimidazole (1 mM) or addition of SKF 525-A (5x10(-4) M) to incubation mixtures significantly inhibited VCN metabolism by 49%, 54% and 37.4% respectively. Activation of VCN to CN- was markedly increased in microsomes obtained from phenobarbital (PB)-treated rats (128.2%). Addition of glutathione (GSH), L-cysteine, D-penicillamine or 2-mercaptoethanol significantly enhanced the release of CN- from VCN 126%, 247%, 202% and 129% of the control value respectively. These findings indicate that VCN is metabolized in the testis via cytochrome P-450 dependent mixed function oxidase system.

Possible functional immunotoxicity of acrylonitrile (VCN).

Acrylonitrile (vinyl cyanide, VCN), an environmental pollutant, has been shown to be an animal and human carcinogen particularly for the GIT. In a previous work done in our laboratory, VCN induced immunosuppressive effects as indicated by a decrease in plaque forming cell (PFC) response to SRBCs (sheep red blood cell) immunization, a marked depletion of spleen lymphocyte subsets by flow cytometric analysis as well as bacterial translocation of the normal flora leading to brachial lymph node abscess. This work was carried out to evaluate the systemic and/or local immunotoxic potential of VCN. Acrylonitrile (2.7 mg kg-1 day-1) was given to CD-1 mice once daily for 5, 10 and 15 days. Immunohistochemical assessment of the number of cells capable of producing IgA in different intestinal compartments (duodenum, jejunum and ileum) revealed a significant decrease following VCN treatment. On the contrary, Bromodeoxyuridine (BrdU) incorporation in gut epithelial cells (duodenum and ileum) showed a significant increase in the same VCN-treated groups of animals. On the other hand, [3H]thymidine uptake was significantly decreased in splenocytes stimulated with phytohemaglutinin (PHA), Concanavalin-A (Con-A) and Lipopolysaccharide (LPS) and derived from animals treated with VCN. The effects of VCN were started after 5 days and increased up to 15 days of daily treatment in most of the investigated parameters. The results suggested that VCN has a profound immunosuppressive effect either systemically or locally which could be a contributing factor in its GIT carcinogenicity.

Renal metabolism of acrylonitrile to cyanide: in vitro studies.

Acrylonitrile (VCN) is a widely used industrial chemical. The present work examines the mechanism of its renal toxicity. In renal centrifugal fractions from Sprague-Dawley rats, the metabolism of VCN to cyanide (CN(-)) was highest in the microsomal fraction and required a NADPH-generating system in the presence of magnesium ions for maximum activity. This biotransformation of VCN to CN(-)was characterised with respect to time (15 min), microsomal protein concentration (3 mg ml(-1)), pH (7.5) and temperature (37 degrees C). The V(max)of the reaction was 118.2 pmol CN(-)mg(-1)protein min(-1)and K(m)was 160.2 micromol VCN. Activation of VCN to CN(-)was markedly increased in microsomes obtained from phenobarbital (PB), ethanol, 4-methylpyrazole and 3-methylcholanthrene-treated rats by 161.5, 89.6, 71.0 and 50.2%, respectively. Addition of SKF 525-A (5x10(-4)m) or benzimidazole (2 m m) to the incubation mixtures significantly inhibited VCN metabolism by 66.6 and 78.8%, respectively. VCN metabolism to CN(-)was enhanced significantly by the addition of 10 m m of glutathione (GSH), l -cysteine, d -penicillamine, cysteamine or 2-mercaptoethanol to 389.5, 886.5, 611. 1, 145.5 and 384.0% of control, respectively. These findings indicate that VCN is metabolised in the kidney via cytochrome P-450-dependent mixed function oxidase system. 1999 Academic Press.

A study on the reproductive toxicity of erythrosine in male mice.

Worldwide usage of different colouring agents in the food industry prompted us to study their toxicity. The potential adverse effects of erythrosine (ER, FD & C Red No. 3) on the spermatogenesis process were investigated in adult mice. Testicular lactic dehydrogenase isoenzyme activity (LDH-X), a pachytene spermatocyte marker of testicular toxicity, was significantly decreased to 71.8% and 68.6% of the control value after daily p.o. administration of ER (21 days) in doses of 68 and 136 mg kg-1 respectively. At the same time, the normal average epididymal sperm count as well as the percentage of motile sperms were significantly inhibited by about 50% and 57% respectively. Moreover, ER was shown to disrupt the normal morphology of the sperm head. Thus, after 5 daily p.o administrations of ER in doses of 680 and 1360 mg kg-1 (equivalent to 10 and 20% of its LD50) it increased the incidence of sperms with abnormal head by about 57% and 65% respectively. The induced increase in sperm abnormalities could enhance the spermatogenic dysfunction and germ cell mutagenicity. These findings indicate that ER in the used doses has a potential toxic effect on spermatogenesis in mice and in turn, it may affect its testicular function and reproductive performance.

Nadolol-glibenclamide interaction: relevance to carbohydrate metabolism in hyperglycaemic rats.

In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect plasma glucose level. Combined administration of ND (10 mg/kg) with GB (0.45 or 0.9 mg/kg) potentiated the hypoglycaemic effect of GB, an effect prominent 4 hours post-treatment. In relevance to the effect of ND and GB interactions towards other aspects of carbohydrate metabolism, co-administration of the two drugs [ND (10 mg/kg) + GB (0.9 mg/kg)] failed to alter the increase in plasma insulin level and the decrease in blood pyruvate and lactate levels induced by GB alone. Concerning liver glycogen, concurrent administration of the two drugs showed a synergistic effect upon its content (257%), while it was 186% for GB treatment, and 179% for ND alone compared to the hyperglycaemic control value. The data revealed that ND potentiates the hypoglycaemic effect of GB, so it is very important to consider this potentiation when the usage of the combined drug regimens is recommended.