Comparative subchronic toxicity of all-trans- and 13-cis-retinoic acid in Sprague-Dawley rats

Hixson, E.Jane; Burdeshaw, J A; Denine, E P; Harrison, Steadman D.

doi:10.1016/0041-008x(79)90331-4

Cited by 45 publications

(15 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, Hixson et al (1979) reported decreased plasma ALB concentrations in male and female rats gavaged with 0.5-5.0 mg kg −1 alltrans-RA or 4.0-40.0 mg kg −1 13-cis-RA for a minimum of 4 weeks and also described the sex effect observed here (increased levels in females). Here it is demonstrated that a shorter duration of treatment at higher all-trans-RA doses was sufficient to decrease ALB levels.…”

Section: Discussionsupporting

confidence: 53%

“…The toxicity of retinoic acids has been studied and characterized for several decades (Zbinden, 1975;Hixson et al, 1979); however, the increased use of 13-cis-RA use in the USA in recent years (Wysowski et al, 2002) has caused rising concern about its potential side effects. One of these side effects is increased cholesterol levels (Lyons et al, 1982;Zech et al, 1983;Marsden et al, 1984;Bershad et al, 1985;Michaelsson et al, 1986;Barth et al, 1993;Fex et al, 1996;Ostlere et al, 1996;Lestringant et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Hixson et al (1979) reported dose-and treatment duration-related alterations of several hematological parameters in rats gavaged daily with 13-cis-RA or all-trans-RA. Albumin levels were decreased in females treated with 0.5-5 mg kg −1 of all-trans-RA for 8-12 weeks; however, the effects in males were less consistent.…”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid

Cisneros¹,

Gough²,

Patton³

et al. 2005

J. Appl. Toxicol.

View full text Add to dashboard Cite

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints.

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid

Cisneros¹,

Gough²,

Patton³

et al. 2005

J. Appl. Toxicol.

View full text Add to dashboard Cite

show abstract

“…In most of these studies, treatment with 13-cis RA has been used. 13-cis RA is isomerized to tRA and/or 9-cis RA in tissues, and activates RAR and/ or RXR (Blaner 2001), with less toxicity (Hixson et al 1979) and a longer half-life (Brazzell et al 1983), compared with tRA. These clinical studies have shown that 20-42% aggressive differentiated thyroid cancer responds to RA treatment by an increase in radioiodide uptake (Simon et al 1996, 1998, 2002a, Grunwald et al 1998, Koerber et al 1999, Gruning et al 2003, Coelho et al 2004.…”

Section: Nis Induction By Nuclear Hormone Receptor Ligandsmentioning

confidence: 99%

Enhancement of sodium/iodide symporter expression in thyroid and breast cancer

Kogai¹,

Taki²,

Brent³

2006

Endocr Relat Cancer

170

150

View full text Add to dashboard Cite

The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a 'cold' or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize b-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10-20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of 'differentiation' agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in 'scan-negative' thyroid cancer and some breast cancer.

show abstract

“…However, changes in alkaline phosphatase were not always associated with bone fractures . Changes in connective tissues are often observed in concert with hepatic toxicity, such as dose-related decreases in plasma albumin (Hixson et al , 1979). .…”

Section: Bone and Co Nnective Tissuementioning

confidence: 99%