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Biomedical subjects

R Dixit

Publications and source records attributed to R Dixit.

At least 73 records · Page 4Linked to original sources
PubMed1981

Acrylamide induced inhibition of hepatic glutathione-S-transferase activity in rats.

Rats injected i.p. with acrylamide (50 mg/kg/day) for 5 days showed a significant inhibition of hepatic glutathione-S-transferase (GST) activity; maximum inhibition occurred in 15-day-old rats in which early development of hind limb paralysis was noted. Addition of acrylamide in vitro to the assay system also inhibited GST activity. No changes were observed in oxidized and reduced glutathione contents.

Acrylamides↗
PubMed1981

In vitro inhibition of alcohol dehydrogenase by acrylamide: interaction with enzyme-SH groups.

Acrylamide, a reactive electrophile, caused a concentration-dependent inhibition of alcohol dehydrogenase (ADH) activity (purified) which was reversed by prior addition of glutathione. Reaction of thiol groups of this enzyme with orthophthalaldehyde (OPT), a fluorescent reagent, exhibited characteristic fluorescence maxima at 330 nm excitation and 420 nm emission. Addition of acrylamide to the enzyme resulted in a concentration-dependent (acrylamide and protein) quenching of fluorescence of thiol groups when compared with fluorescence quenching caused by N-ethylmaleimide (NEM), a known thiol ligand. The results demonstrate that acrylamide-induced inhibition of purified ADH activity is mediated through its specific interaction with -SH groups in the enzyme molecule.

Acrylamides↗
PubMed1981

Glutathione-S-transferase activity in the brain: species, sex, regional, and age differences.

Glutathione-S-transferase activity in the brain of male mammals (rat and mouse) was found to be relatively lower than in that of females. In contrast, the male aves (pigeon, kite, vulture, and crow) exhibited comparatively higher activity in brain glutathione-S-transferase than the corresponding females. Postnatal development of cytosolic glutathione-S-transferase activity in the rat brain was also investigated. The day-7 rats showed a low activity of 48 nmol/min/mg protein that gradually increased 3.2-fold over the age of 28 days. No striking differences in brain enzyme activities were observed between the 35- and 90-day-old rats. Discrete brain regions of immature rats were found to possess considerable but lower quantities of glutathione-S-transferase activity than those of the adults. The activity increased with the onset of development and attained a steady state after 21 days of age.

Aging↗
PubMed1981

Effect of styrene on hepatic mixed function oxidases, glutathione content and glutathione-s-transferase activity in rats.

Effect of styrene administration (250, 450 and 900 mg/kg orally for 7 consecutive days) on hepatic mixed function oxidase (MFO) enzyme activities, glutathione content and glutathione-S-transferase activity were observed. Activity of aryl hydrocarbon hydroxylase and aniline hydroxylase was significantly enhanced at higher doses of styrene (450 and 900 mg/kg). A significant lowering of glutathione content accompanied with the inhibition of glutathione-S-transferase activity was also noticed at the highest dose of styrene (900 mg/kg).

Aniline Hydroxylase↗
PubMed1981

Preliminary evidence for the presence of glutathione-s-transferase activity in mammalian and avian brain.

Glutathione-S-transferase activity has been demonstrated in the brain of rabbit, guinea pig, rat, mouse, and pigeon. The activity was in the following order: rabbit > (guinea pig = mouse) > rat > pigeon. The activity of brain was about 1/3 to 1/9 of that present in liver depending upon the species. In the rat brain glutathione-S-transferase activity was found to be distributed equally in cerebrum, cerebellum, and brain stem and localized mainly in the organelle-free cytosol fraction.

Animals↗
PubMed1980

Effect of diethyl maleate on acrylamide induced neuropathy in rats.

Pre-administration of diethyl maleate (DEM) to rats resulted in an earlier onset and development of hind limb paralysis following acrylamide administration than in rats treated with acrylamide only. A marked depletion of brain biogenic amine content and of glutathione levels was also observed in the DEM pretreated groups. Depletion of cellular glutathione would appear to lead to an increased neurotoxicity of acrylamide.

Acrylamides↗
PubMedDate not supplied

Hydrocolonic sonography in the evaluation of colonic lesions.

BACKGROUND: The present study was done to assess the sensitivity, specificity, ease of examination, and limitations of hydrocolonic sonography (HCS) to evaluate a heterogeneous spectrum of colonic disorders. METHODS: In a prospective study, 100 patients (53 male, 47 female) with clinical suspicion of colonic abnormality were examined by conventional abdominal sonography, HCS, and colonoscopy on the same day. The patients then underwent appropriately planned barium studies. Histopathologic diagnosis was established by colonoscopic/excision biopsies or fine needle aspiration cytology (FNAC) whenever indicated and results correlated. RESULTS: In 94% of patients, it was possible to evaluate the entire colon from the rectosigmoid junction to the cecum. Redundant parts of the colon were not well evaluated by this technique. The rectum could not be adequately evaluated, and rectal examination was not included in the study. HCS can evaluate in great detail both the colonic lumen and wall and, hence, could suggest the nature of the lesion in the majority (87.9%) of cases based on characteristic changes in wall stratification, echogenicity, lumenal changes, and site and length of involvement, although distinguishing between benign and malignant lesions was not always possible. In 93% of patients with tuberculous colitis/ileocolitis, the normal wall stratification was no longer in evidence, with moderate hypoechoic thickening of the wall (average = 8.34 mm). Malignant lesions (93.7%) showed grossly thickened bowel wall with loss of stratification and hypoechoic/heterogeneous echo texture. Intralumenal polypoid masses also were seen in 87.5% of cases, and there was extension beyond the adventitia and involvement of pericolonic tissues in 75% of cases. All patients with ulcerative colitis had only mild hypoechoic wall thickening; the five-layer structure could be clearly discerned in 87.5% of cases. HCS had an overall sensitivity of 90.9% and a specificity of 94.7% in this study. CONCLUSIONS: HCS can be advantageously used for diagnosis and differential diagnosis of inflammatory and malignant colonic lesions and also for follow-up of patients with chronic inflammatory large bowel diseases such as ulcerative colitis.

Adolescent↗
PubMedDate not supplied

Need for dietary control by caloric restriction in rodent toxicology and carcinogenicity studies.

The conditions under which laboratory animals are maintained can powerfully influence the results of toxicological studies utilized for risk assessment. Nutrition is of importance in toxicological bioassays and research, because diet composition and the conditions under which it is fed can affect the metabolism and activity of xenobiotic test substances and alter the results and reproducibility of long-term studies. It is known that ad libitum (AL) overfed sedentary laboratory rodents suffer from an early onset of degenerative disease and diet-related tumors that lead to poor survival in chronic bioassays. AL-fed animals are not well-controlled subjects for any experimental studies. Examination of study-to-study variability in food consumption, body weight, and survival in carcinogenicity studies for the same strain or stock of rodents shows tremendous laboratory-to-laboratory variability. However, a significant correlation between average food (calorie) consumption, adult body weight, and survival has been clearly established. The use of moderate dietary restriction (DR) results in a better controlled rodent model with a lower incidence or delayed onset of spontaneous diseases and tumors. Operationally simple, moderate DR significantly improves survival, controls adult body weight and obesity, reduces age-related renal, endocrine, and cardiac diseases, increases exposure time, and increases the statistical sensitivity of these expensive, chronic bioassays to detect a true treatment effect. A moderate DR regimen of 70-75% of the maximum unrestricted AL food intake is recommended as a nutritionally intelligent, well-established method in conducting well-controlled toxicology and carcinogenicity studies.

Animals↗
PubMedDate not supplied

The effects of diet, ad libitum overfeeding, and moderate dietary restriction on the rodent bioassay: the uncontrolled variable in safety assessment.

Ad libitum (AL) overfeeding is the most significant, uncontrolled variable affecting the outcome of the current rodent bioassay. There is a highly significant correlation between AL food consumption, the resultant obesity and body weight, and low 2-yr survival in rodents. AL feeding of diets with lowered protein, metabolizable energy (ME), and increased fiber does not improve survival. Only dietary restriction (DR) of all diets tested significantly improves survival and delays the onset of spontaneous degenerative disease (i.e., nephropathy and cardiomyopathy) and diet-related tumors. Moderate DR results in an incidence of spontaneous tumors similar to AL-fed rats, but the tumors are found incidentally and do not cause early mortality. There is a decreased age-adjusted incidence of pituitary and mammary gland tumors in moderate DR-fed rats, but tumor growth time is similar between AL and DR rats with only a delay in tumor onset time seen in DR-fed groups. Moderate DR does not significantly alter drug-metabolizing enzyme activities nor the toxicologic response to 5 pharmaceuticals tested at maximum tolerated doses (MTDs). However, moderate DR-fed rats did require much higher doses of 4 additional pharmaceutical compounds before classical MTDs were produced. Toxicokinetic studies of 2 of these compounds demonstrated equal or higher steady-state systemic exposures to parent drug and metabolites in moderate DR-fed rats. Markers of oxidative stress (lipid peroxidation, protein oxidation) are decreased and cytoprotective anti-oxidant markers are preserved in moderate DR-fed rats. But moderate DR does not delay reproductive senescence in female rats. Only marked DR delays reproductive senescence compared to AL and moderate DR-fed female rats. These and other data indicate that moderate DR is the most appropriate method of dietary control for the rodent bioassay when used to assess pharmaceuticals for human safety and compounds for risk assessment.

Animal Feed↗