A review of the role of tissue repair as an adaptive strategy: Why low doses are often non-toxic and why high doses can be fatal

Calabrese, E.J.; Mehendale, Harihara M.

doi:10.1016/0278-6915(95)00101-8

Cited by 39 publications

(19 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A growing number of mammalian examples also exists where plausible explanatory mechanisms have been put forth to account for specific hormetic dose-response relationships (11)(12)(13)(14)(15).…”

Section: Why Is Hormesis Infrequently Observed?mentioning

confidence: 99%

Hormesis as a biological hypothesis.

Calabrese

Baldwin

1998

Environ Health Perspect

150

View full text Add to dashboard Cite

Section: Why Is Hormesis Infrequently Observed?mentioning

confidence: 99%

Hormesis as a biological hypothesis.

Calabrese

Baldwin

1998

Environ Health Perspect

150

View full text Add to dashboard Cite

“…While studies have shown that nutritional status is an important factor in determining susceptibility to toxic chemicals (Chanda and Mehendale, 1996a), it is also known that survival after hepatocellular injury and necrosis may depend on the ability of the remaining hepatocytes to divide and restore an adequate population of functioning cells Mehendale, 1994, 1996b). Several studies have established the critical role of liver cell division and compensatory tissue repair (Calabrese and Mehendale, 1996;Mehendale, 1991;Mehendale et al, 1994). Thioacetamide, originally used as a fungicide, is a potent model hepatotoxicant and exposure to environmental agents like this is known to cause liver injury leading to hepatitis and fulminant hepatic failure .…”

Section: Consequencementioning

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

“…In addition to toxic response, however, tissue repair, a simultaneous biologic compensatory response that accompanies chemical-induced injury, also needs due consideration (1,2). Several studies suggest that the rate and extent of tissue repair as a response to the injury inflicted by toxicants determines the ultimate outcome of hepatotoxicity (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Blockage of the tissue repair leads to progression of injury, culminating in hepatic failure and death (9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

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

A review of the role of tissue repair as an adaptive strategy: Why low doses are often non-toxic and why high doses can be fatal

Cited by 39 publications

References 36 publications

Hormesis as a biological hypothesis.

Hormesis as a biological hypothesis.

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