The toxicity of chemically deglycosylated ricin A-chain in mice

A. M. Soler-Rodriguez, J. W. Uhr, J. Richardson, E. S. Vitetta

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side-effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in "second generation" immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-α. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites.

Original languageEnglish (US)
Pages (from-to)281-291
Number of pages11
JournalInternational Journal of Immunopharmacology
Volume14
Issue number2
DOIs
StatePublished - 1992

Fingerprint

Ricin
Ascites
Immunotoxins
Weight Loss
Neoplasm Antibodies
Rhabdomyolysis
SCID Mice
Aphasia
Myalgia
Pulmonary Edema
Renal Insufficiency
Blood Vessels
Immune System
Rodentia
Fever
Injections
Liver
Serum

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

The toxicity of chemically deglycosylated ricin A-chain in mice. / Soler-Rodriguez, A. M.; Uhr, J. W.; Richardson, J.; Vitetta, E. S.

In: International Journal of Immunopharmacology, Vol. 14, No. 2, 1992, p. 281-291.

Research output: Contribution to journalArticle

@article{531a296283394fb291ed24f49d2c64f2,
title = "The toxicity of chemically deglycosylated ricin A-chain in mice",
abstract = "Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side-effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in {"}second generation{"} immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-α. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites.",
author = "Soler-Rodriguez, {A. M.} and Uhr, {J. W.} and J. Richardson and Vitetta, {E. S.}",
year = "1992",
doi = "10.1016/0192-0561(92)90041-I",
language = "English (US)",
volume = "14",
pages = "281--291",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - The toxicity of chemically deglycosylated ricin A-chain in mice

AU - Soler-Rodriguez, A. M.

AU - Uhr, J. W.

AU - Richardson, J.

AU - Vitetta, E. S.

PY - 1992

Y1 - 1992

N2 - Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side-effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in "second generation" immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-α. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites.

AB - Tumor-reactive antibodies coupled to ricin or its A-chain (immunotoxins) have been used in rodents and humans to treat a variety of neoplastic diseases. Side-effects of such treatment include hepatotoxicity, vascular leak syndrome, myalgia and low grade fever. At high doses, severe toxicities include liver damage, pulmonary edema, aphasia, rhabdomyolysis and kidney failure. There have been a limited number of toxicologic studies on uncoupled ricin or its A-chain and none on deglycosylated A-chain. Since the latter has been utilized in "second generation" immunotoxins, the current studies were carried out to evaluate the toxicities induced by deglycosylated ricin A-chain (dgA) in mice. The administration of dgA to normal BALB/c mice causes early (24 h) weight loss and late (10 day) accumumulation of ascites. These effects could be partially altered by changing the route of injection of dgA from i.v. to i.p. Thus, i.p. administration caused weight loss but not ascites, whereas i.v. administration caused both. Weight loss was associated with reduced fluid intake by the treated mice, and was not associated with increased levels of serum TNF-α. SCID mice injected with the same dose of dgA as normal BALB/c mice developed ascites, but it was of lesser severity, suggesting that a functional immune system, differences in microbial flora, or strain differences may be involved in the development of ascites.

UR - http://www.scopus.com/inward/record.url?scp=0026503802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026503802&partnerID=8YFLogxK

U2 - 10.1016/0192-0561(92)90041-I

DO - 10.1016/0192-0561(92)90041-I

M3 - Article

C2 - 1624227

AN - SCOPUS:0026503802

VL - 14

SP - 281

EP - 291

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 2

ER -