Retinoid : Retinoids are a type of chemical compound that are chemically related to vitamin A. They are used in medicine, mainly due to their action on the growth of epithelial cells. Retinoids have many important functions in the body, including an important role in vision, regulation of cell proliferation and differentiation, bone growth, immune function, and activation of tumor suppressor genes. Research is underway on its abilities to treat different types of skin cancers. Currently 9-cis-retinoic acid is used topically in the treatment of Kaposi ‘s Sarcoma .
Summary
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- 1 Types
- 2 Can be divided into 3 generations
- 3 Structure
- 4 Absorption
- 5 Uses
- 6 Synthesis
- 7 Toxicity
- 8 Sources
Types
They can be divided into 3 generations
- 1st generation: retinol, retinal , tretinoin ( retinoic acid , Retin-A ), isotretinoin , and alitretinoin .
- 2nd generation: etretinateand its metabolite acitretin .
- 3rd generation: tazarotene, bexarotene and adapalene .
Structure
The basic structure of a retinoid molecule consists of a cyclic end group, a polyene side chain, and a polar end group. The conjugated system formed by the alternating C = C double bonds in the polyene side chain are responsible for the color of the retinoids (generally yellow, orange or red). Therefore, many retinoids are chromophores. The alternation of side chains and end groups create the various classes of retinoids.
The first and second generation of retinoids are able to bind to various retinoid receptors due to their flexibility, caused by their alternating single and double bonds. The third generation of retinoids are less flexible than the first and second generations, therefore they interact with fewer retinoid receptors.
Absorption
The main source of dietary retinoids are retinyl esters derived from animal sources. Retinyl esters are hydrolyzed in the intestinal lumen to produce free retinol and the corresponding fatty acid (i.e. palmitate or stearate). After hydrolysis , retinol is absorbed by the enterocytes . The hydrolysis of retinyl esters requires the presence of bile salts that serve to solubilize retinyl esters in mixed micelles and to activate hydrolyzing enzymes.
Various enzymes that are present in the intestinal lumen may be involved in the hydrolysis of dietary retinyl esters. Cholesterol esterase is secreted into the intestinal lumen from the pancreas and has been shown in vitro to show retinyl ester hydrolase activity. Furthermore, a retinyl ester hydrolase that is intrinsic to the brush border membrane of the small intestine has been characterized in the rat as well as in the human. Different hydrolyzing enzymes are activated by different types of bile salts and have different substrate specificities. For example, while pancreatic esterase is selective for short-chain retinyl esters, the brush border membrane enzyme preferably hydrolyzes retinyl esters containing a long chain fatty acid such as palmitate or stearate. Retinol enters the absorption cells of the small intestine, preferably in the all-trans-retinol form.
Applications
Retinoids are used in the treatment of many diverse diseases and are effective in the treatment of a number of dermatological conditions such as inflammatory skin disorders, skin cancers, disorders of increased cell turnover (eg psoriasis) , and photoaging.
Common skin conditions treated with retinoids include acne and psoriasis. The isotretinoin is not only considered the only known cure for acne in some patients, but was originally a chemotherapy treatment for certain types of cancers, such as leukemia.
Synthesis
Retinoids can be synthesized in a variety of ways. A common procedure to reduce retinoic toxicity and improve retinoic activity is glucuronidation. They have proposed a novel synthesis to achieve glucuronidation.
Toxicity
The toxic effects occur with a prolonged high intake. Specific toxicity is related to exposure time and exposure concentration. A clinical sign of chronic poisoning is the presence of painful tender swellings in the long bones. Anorexia, skin lesions, alopecia (hair loss), hepatosplenomegaly , papilla edema , hemorrhage , general malaise , intracranial hypertension , and death could also occur .
Chronic overdose also causes an increased lability of the biological membranes and the outer layer of the skin to peel. Recent research has suggested a role for retinoids in cutaneous adverse effects in a variety of medications including the antimalarial proguanil. Medications such as proguanil are proposed to act by altering retinoid homeostasis . Systemic retinoids (isotretinoin, etretinate) are contraindicated during pregnancy as they can cause CNS defects, cranio-facial, cardiovascular and other defects.
