Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats

Kulkarni, Swarupa G.; Warbritton, Alan; Bucci, Thomas J.; Mehendale, Harihara M.

doi:10.1016/s0300-483x(97)03627-5

Cited by 30 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Firstly, it represents a specific event in cellular proliferation, rather than the raw sum of events that are described by thymidine. This can be useful in identifying DNA synthesis inhibition effects and cellcycle related anomalies known to be induced by certain drugs [10], but otherwise not studied, especially in allergy. Nevertheless, when no such interferences exist, PCNA expression has been shown to correlate very well with thymidine incorporation [11]and this was confirmed in our own preliminary experiments (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Lymphocyte Proliferating Cell Nuclear Antigen Expression with Dietary Cow’s Milk Antigen Load in Infants with Allergy to Cow’s Milk

Papadopoulos

Syrigou

Bossios

et al. 1999

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Controversial results have been reported on the participation and diagnostic value of lymphocyte reactivity in cow’s milk (CM) allergy. In this study, we used a specific nuclear marker to evaluate lymphocyte proliferation in IgE–mediated CM allergy in infants, and examine its relation with diets containing different CM antigen loads. Methods: Infants with IgE–mediated CM allergy, as assessed by open provocation and RAST, were grouped according to their exclusive diet, either CM formulae, breast feeding, or hydrolysed whey formulae. A group of non–atopic infants receiving CM was also examined. Lymphocyte proliferation to β–lactoglobulin was evaluated by quantitation of the proliferating cell nuclear antigen (PCNA) expression in peripheral blood mononuclear cells, by flow cytometry. Immunophenotypic surface markers were also examined. Results: A marked difference of PCNA expression between CM–fed allergic infants and healthy controls was observed (p<0.001). In this setting, PCNA expression ≥10% was highly specific and sensitive as a marker of CM allergy in CM–fed infants. Moreover, a significant correlation (p<0.001) between antigen load and PCNA was established in CM–allergic infants under different diets, higher values obtained with increasing antigen loads. In addition, within the group fed hydrolyzed formulae, low–molecular–weight products resulted in marginally lower PCNA expression than higher–molecular–weight formulae. No differences in immunophenotype were found, with the exception of a higher CD23 expression in the breast–fed group. Conclusions: PCNA could be a useful marker in the assessment of lymphocyte proliferation to CM antigens. Low CM antigen diets are related with reduced lymphocyte reactivity, which may partly explain the clinical benefit observed with such diets.

show abstract

Section: Discussionmentioning

confidence: 99%

Correlation of Lymphocyte Proliferating Cell Nuclear Antigen Expression with Dietary Cow’s Milk Antigen Load in Infants with Allergy to Cow’s Milk

Papadopoulos

Syrigou

Bossios

et al. 1999

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…Highly stimulated compensatory tissue repair is a biological response that follows partial hepatectomy or chemical-induced injury (Michalopoulus, 1990;Chanda et al, 1995;Kulkarni et al, 1997). In chemical hepatectomy, the regeneration response is a dose-related event in which cell division and tissue repair occur in a dose-dependent fashion until a threshold is reached, beyond which injury results in lethality due to unrestrained progression of injury (Mangipudy et al, 1995a;Mehendale, 1994;Rao et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…PCNA studies were conducted in order to confirm stimulated cell division and cell cycle progression suggested by 3 H-T incorporation studies. Each liver section was quantified for different cells in the cell cycle by counting 1000 cells in 10 high-power fields (Kulkarni et al, , 1997Rao et aL, 1996). liver glycogen levels.…”

Section: In Vivo Incorporation Of [mentioning

confidence: 99%

Temporal Changes in Tissue Repair Permit Survival of Diet-Restricted Rats from an Acute Lethal Dose of Thioacetamide

Ramaiah¹

1998

Toxicological Sciences

View full text Add to dashboard Cite

“…These findings suggest that even though massive (and ordinarily lethal) injury may occur because of modulation of stage one, enhanced tissue repair in stage two can compensate, thereby allowing the reversal of injury. Antimitotic intervention of cell division by colchicine administration after the mechanistic processes of infliction of injury (stage one) leads to progression of even limited injury culminating in lethal outcome from ordinarily nonlethal doses of hepatotoxicants (9,11,79).…”

Section: Implications To Therapeutic Strategiesmentioning

confidence: 99%

Role of tissue repair in toxicologic interactions among hepatotoxic organics.

Soni

Mehendale

1998

Environ Health Perspect

View full text Add to dashboard Cite

It is widely recognized that exposure to combinations or mixtures of chemicals may result in highly exaggerated toxicity even though individual chemicals might not be toxic at low doses. Chemical mixtures may also cause additive or less than additive toxicity. From the perspective of public health, highly exaggerated toxicity is of significant concern. Assessment of risk from exposure to chemical mixtures requires knowledge of the underlying mechanisms. Previous studies from this laboratory have shown that nontoxic doses of chlordecone (10 ppm, 15 days) and carbon tetrachloride (CCl4) (100 microliters/kg) interact at the biologic interface, resulting in potentiated liver injury and 67-fold amplification of CCl4 lethality. In contrast, although interaction between phenobarbital and CCl4 leads to even higher injury, animal survival is unaffected because of highly stimulated compensatory tissue repair. A wide variety of additional experimental evidence confirms the central role of stimulated tissue repair as a decisive determinant of the final outcome of liver injury inflicted by hepatotoxicants. These findings led us to propose a two-stage model of toxicity. In this model, tissue injury is inflicted in stage one by the well-described mechanisms of toxicity, whereas in stage two the ultimate toxic outcome is determined by whether timely and sufficient tissue repair response accompanies this injury. In an attempt to validate this model, dose-response relationships for injury and tissue repair as opposing responses have been developed for model hepatotoxicants. Results of these studies suggest that tissue repair increases in a dose-dependent manner, restraining injury up to a threshold dose, whereupon it is inhibited, allowing an unrestrained progression of injury. These findings indicate that tissue repair is a quantifiable response to toxic injury and that inclusion of this response in risk assessment may help in fine-tuning prediction of toxicity outcomes. Images Figure 3 Figure 4 Figure 6

show abstract

Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats

Cited by 30 publications

References 26 publications

Correlation of Lymphocyte Proliferating Cell Nuclear Antigen Expression with Dietary Cow’s Milk Antigen Load in Infants with Allergy to Cow’s Milk

Correlation of Lymphocyte Proliferating Cell Nuclear Antigen Expression with Dietary Cow’s Milk Antigen Load in Infants with Allergy to Cow’s Milk

Temporal Changes in Tissue Repair Permit Survival of Diet-Restricted Rats from an Acute Lethal Dose of Thioacetamide

Role of tissue repair in toxicologic interactions among hepatotoxic organics.

Contact Info

Product

Resources

About