Comparative assessment of the toxicology of vitamin A and retinoids in man

Knockout of Cyp26a1 and Cyp26b1 during postnatal life causes reduced lifespan, dermatitis, splenomegaly, and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 −/− b1 −/− mice is very similar to the observed phenotype in mice and rats after chronic dosing with at RA. While acute at RA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight, 12,15 chronic at RA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis, 14 findings that are very similar to the phenotype observed in this study. The observations that exogenous at RA clearance was reduced in the Cyp26a1 −/− b1 −/− mice by 80% and the Cyp26a1 −/− b1 −/− mice were hypersensitive to at RA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing at RA in postnatal animals.…”

Knockout of Cyp26a1 and Cyp26b1 during postnatal life causes reduced lifespan, dermatitis, splenomegaly, and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 −/− b1 −/− mice is very similar to the observed phenotype in mice and rats after chronic dosing with at RA. While acute at RA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight, 12,15 chronic at RA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis, 14 findings that are very similar to the phenotype observed in this study. The observations that exogenous at RA clearance was reduced in the Cyp26a1 −/− b1 −/− mice by 80% and the Cyp26a1 −/− b1 −/− mice were hypersensitive to at RA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing at RA in postnatal animals.…”

Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis

“…Because TLZ has shown therapeutic efficacy in congenital ichthyosis, psoriasis, and acne vulgaris in human trials, with an acceptable safety profile ( 56 ), our experimental findings make a compelling case for testing a RAMBA to modify disease in OA. Our data, as well as others, suggest that RAMBAs keep atRA within acceptable physiological concentrations and thus are unlikely to lead to toxicity such as that seen with hypervitaminosis A ( 65 , 66 ).…”

Knockout of Cyp26a1 and Cyp26b1 during post-natal life causes reduced lifespan, dermatitis, splenomegaly and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 -/-b1 -/mice is very similar to the observed phenotype in mice and rats after chronic dosing with atRA. While acute atRA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight (Kretzschmar and Leuschner, 1975;Biesalski, 1989), chronic atRA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis (Kurtz et al, 1984), findings that are very similar to the phenotype observed in this study. The observations that exogenous atRA clearance was reduced in the Cyp26a1 -/-b1 -/mice by 80% and the Cyp26a1 -/-b1 -/mice were hypersensitive to atRA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing atRA in post-natal animals.…”

Knockout of Cyp26a1 and Cyp26b1 during postnatal life causes reduced lifespan, dermatitis, splenomegaly, and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 −/− b1 −/− mice is very similar to the observed phenotype in mice and rats after chronic dosing with at RA. While acute at RA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight, 12,15 chronic at RA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis, 14 findings that are very similar to the phenotype observed in this study. The observations that exogenous at RA clearance was reduced in the Cyp26a1 −/− b1 −/− mice by 80% and the Cyp26a1 −/− b1 −/− mice were hypersensitive to at RA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing at RA in postnatal animals.…”

Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis

“…Because TLZ has shown therapeutic efficacy in congenital ichthyosis, psoriasis, and acne vulgaris in human trials, with an acceptable safety profile ( 56 ), our experimental findings make a compelling case for testing a RAMBA to modify disease in OA. Our data, as well as others, suggest that RAMBAs keep atRA within acceptable physiological concentrations and thus are unlikely to lead to toxicity such as that seen with hypervitaminosis A ( 65 , 66 ).…”

Knockout of Cyp26a1 and Cyp26b1 during post-natal life causes reduced lifespan, dermatitis, splenomegaly and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 -/-b1 -/mice is very similar to the observed phenotype in mice and rats after chronic dosing with atRA. While acute atRA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight (Kretzschmar and Leuschner, 1975;Biesalski, 1989), chronic atRA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis (Kurtz et al, 1984), findings that are very similar to the phenotype observed in this study. The observations that exogenous atRA clearance was reduced in the Cyp26a1 -/-b1 -/mice by 80% and the Cyp26a1 -/-b1 -/mice were hypersensitive to atRA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing atRA in post-natal animals.…”

Knockout of Cyp26a1 and Cyp26b1 during postnatal life causes reduced lifespan, dermatitis, splenomegaly, and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 −/− b1 −/− mice is very similar to the observed phenotype in mice and rats after chronic dosing with at RA. While acute at RA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight, 12,15 chronic at RA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis, 14 findings that are very similar to the phenotype observed in this study. The observations that exogenous at RA clearance was reduced in the Cyp26a1 −/− b1 −/− mice by 80% and the Cyp26a1 −/− b1 −/− mice were hypersensitive to at RA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing at RA in postnatal animals.…”

Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis

“…Because TLZ has shown therapeutic efficacy in congenital ichthyosis, psoriasis, and acne vulgaris in human trials, with an acceptable safety profile ( 56 ), our experimental findings make a compelling case for testing a RAMBA to modify disease in OA. Our data, as well as others, suggest that RAMBAs keep atRA within acceptable physiological concentrations and thus are unlikely to lead to toxicity such as that seen with hypervitaminosis A ( 65 , 66 ).…”

Knockout of Cyp26a1 and Cyp26b1 during post-natal life causes reduced lifespan, dermatitis, splenomegaly and systemic inflammation in mice

“…The phenotype observed in the Cyp26a1 -/-b1 -/mice is very similar to the observed phenotype in mice and rats after chronic dosing with atRA. While acute atRA toxicity results in hair loss, dermal and mucosal alterations and loss of body weight (Kretzschmar and Leuschner, 1975;Biesalski, 1989), chronic atRA treatment has been shown to cause lymphoid hyperplasia, extramedullary hematopoiesis and hyperkeratosis (Kurtz et al, 1984), findings that are very similar to the phenotype observed in this study. The observations that exogenous atRA clearance was reduced in the Cyp26a1 -/-b1 -/mice by 80% and the Cyp26a1 -/-b1 -/mice were hypersensitive to atRA toxicity, further confirm the critical role of Cyp26a1 and Cyp26b1 in clearing atRA in post-natal animals.…”