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Repeated intravenius doses of all-trans-retinoyl B-D-glucuronide is not effectiv in the treatment of

نویسنده:
Jack M. Gallup
,
Branka Grubor
,
Arun B. Barua
,
غلامرضا محمدی
,
Kim A. Brogden
,
James A. Olson
,
Mark R. Ackermann
,
Gholam Reza Mohammadi
سال
: 2001
چکیده: All-trans-retinoyl β-D-glucuronide, a water-soluble glucuronic acid conjugate of all-transretinoic

acid, has demonstrated high biological activity and low toxicity in most in vitro and in

vivo models. Since the reparative effects of retinoids on epithelium are well-known, our aim

was to study the effect(s) of intravenously-administered all-trans-retinoyl β-D-glucuronide in

lambs with chronic bacterial bronchopneumonia.

Material/Methods: Two groups of lambs were inoculated intrabronchially with either pyrogen-free saline or

Mannheimia haemolytica. Thirty-three days later, lambs were injected four times at five-day

intervals with 2 mL of 116 mM all-trans-retinoyl β-D-glucuronide (6.0–9.3 μmol/kg or

2.86–4.42 mg/kg animal body weight) in dimethyl sulfoxide, or dimethyl sulfoxide alone.

Animal behavior and signs of clinical illness were logged daily. Lung and liver samples were

assessed for histopathology, while serum and liver samples were extracted for retinoids and

analyzed by reversed-phase gradient high-performance liquid chromatography.

Results: Repeated injections of highly concentrated all-trans-retinoyl β-D-glucuronide did not cause

changes in appetite, activity or other behaviors nor did it cause histologic lesions in liver and

lung. However, it had no effect on resolution of lung lesions resultant of chronic Mannheimia

haemolytica bronchopneumonia.

Conclusion: Repeated intravenous administration of high amounts of all-trans-retinoyl β-D-glucuronide to

lambs did not elicit signs of gross or microscopic toxicity. However, administering all-transretinoyl

β-D-glucuronide too late in the progression of bacterial pneumonia is thought to be

the main reason for its lack of effect in this model. A retinoid lactone derivative was detected

in sheep serum and liver several days after treatment.
یو آر آی: http://libsearch.um.ac.ir:80/fum/handle/fum/3401943
کلیدواژه(گان): retinoids • RAG • toxicity • bronchopneumonia • intravenous injection • lesions
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    Repeated intravenius doses of all-trans-retinoyl B-D-glucuronide is not effectiv in the treatment of

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contributor authorJack M. Gallupen
contributor authorBranka Gruboren
contributor authorArun B. Baruaen
contributor authorغلامرضا محمدیen
contributor authorKim A. Brogdenen
contributor authorJames A. Olsonen
contributor authorMark R. Ackermannen
contributor authorGholam Reza Mohammadifa
date accessioned2020-06-06T14:33:44Z
date available2020-06-06T14:33:44Z
date issued2001
identifier urihttp://libsearch.um.ac.ir:80/fum/handle/fum/3401943?locale-attribute=fa
description abstractAll-trans-retinoyl β-D-glucuronide, a water-soluble glucuronic acid conjugate of all-transretinoic

acid, has demonstrated high biological activity and low toxicity in most in vitro and in

vivo models. Since the reparative effects of retinoids on epithelium are well-known, our aim

was to study the effect(s) of intravenously-administered all-trans-retinoyl β-D-glucuronide in

lambs with chronic bacterial bronchopneumonia.

Material/Methods: Two groups of lambs were inoculated intrabronchially with either pyrogen-free saline or

Mannheimia haemolytica. Thirty-three days later, lambs were injected four times at five-day

intervals with 2 mL of 116 mM all-trans-retinoyl β-D-glucuronide (6.0–9.3 μmol/kg or

2.86–4.42 mg/kg animal body weight) in dimethyl sulfoxide, or dimethyl sulfoxide alone.

Animal behavior and signs of clinical illness were logged daily. Lung and liver samples were

assessed for histopathology, while serum and liver samples were extracted for retinoids and

analyzed by reversed-phase gradient high-performance liquid chromatography.

Results: Repeated injections of highly concentrated all-trans-retinoyl β-D-glucuronide did not cause

changes in appetite, activity or other behaviors nor did it cause histologic lesions in liver and

lung. However, it had no effect on resolution of lung lesions resultant of chronic Mannheimia

haemolytica bronchopneumonia.

Conclusion: Repeated intravenous administration of high amounts of all-trans-retinoyl β-D-glucuronide to

lambs did not elicit signs of gross or microscopic toxicity. However, administering all-transretinoyl

β-D-glucuronide too late in the progression of bacterial pneumonia is thought to be

the main reason for its lack of effect in this model. A retinoid lactone derivative was detected

in sheep serum and liver several days after treatment.
en
languageEnglish
titleRepeated intravenius doses of all-trans-retinoyl B-D-glucuronide is not effectiv in the treatment ofen
typeJournal Paper
contenttypeExternal Fulltext
subject keywordsretinoids • RAG • toxicity • bronchopneumonia • intravenous injection • lesionsen
journal titleMedical Science Monitorfa
pages345-353
journal volume8
journal issue9
identifier linkhttps://profdoc.um.ac.ir/paper-abstract-200348.html
identifier articleid200348
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