Drug–Biomolecule Interactions: Drug Toxicity and Vitamin Coenzyme Depletion

Bederka, John P.; Davitiyananda, Danis; Moses, Mikel L.; Ahmad, Nasim

doi:10.1002/jps.2600640345

Cited by 8 publications

(3 citation statements)

References 26 publications

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“…Adult female Swiss albino and Charles River mice were used in a study by Bederka et al (1975). The LD25 after intraperitoneal injection of Niacin to approximately 160 mice was 3.1 g/kg bw.…”

Section: Tablementioning

confidence: 99%

Final Report of the Safety Assessment of Niacinamide and Niacin1

2005

Int J Toxicol

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Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic aromatic compounds which function in cosmetics primarily as hair and skin conditioning agents. Niacinamide is used in around 30 cosmetic formulations including shampoos, hair tonics, skin moisturizers, and cleansing formulations. Niacin is used in a few similar product types. The concentration of use of Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in body and hand creams, lotions, powders and sprays. Niacin concentrations of use range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in paste masks (mud packs). Both ingredients are accepted for use in cosmetics in Japan and the European Union. Both are GRAS direct food additives and nutrient and/or dietary supplements. Niacinamide may be used in clinical treatment of hypercholesteremia and Niacin in prevention of pellegra and treatment of certain psychological disorders. Both ingredients are readily absorbed from skin, blood, and the intestines and widely distribute throughout the body. Metabolites include N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is primarily through the urinary tract. While Niacinamide is more toxic than Niacin in acute toxicity studies, both are relatively non-toxic. Short-term oral, parenteral, or dermal toxicity studies did not identify significant irreversible effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation, was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in actual formulations produced mostly non-irritant reactions, with only some marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide in rabbits produced only marginal irritation. Skin sensitization tests of Niacinamide at 5% during induction and 20% during challenge were negative in guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or without metabolic activation. Niacinamide and Niacin at 2 mg/ml were negative in a chromosome aberration test in Chinese hamster ovary cells, but did produce large structural chromosome aberrations at 3 mg/ml. Niacinamide induced sister chromatid exchanges in Chinese hamster ovary cells, but Niacin did not. Under certain circumstances, Niacinamide can cause an increase in unscheduled DNA synthesis in human lymphocytes treated with UV or a nitrosoguanidine compound. Niacinamide itself was not carcinogenic when administered (1%) in the drinking water of mice. No data on the carcinogenic effect of Niacin were available. Niacinamide can moderate the induction of tumors by established carcinogens. Niacinamide in combination with streptozotocin (a nitrosourea compound) or with heliotrine (a pyrrolizidine alkaloid), produced pancreatic islet tumors. On the other hand, Niacinamide reduced the renal adenomas produced by streptozotocin; and intestinal and bladder tumors induced by a preparation of bracken fern. Niacinamide evaluated in in vitro test systems did affect development, but Niacinamide re...

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Section: Tablementioning

confidence: 99%

Final Report of the Safety Assessment of Niacinamide and Niacin1

2005

Int J Toxicol

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“…1-(3-Pyridyl)ethanol (5), the reduced form of 2, is involved in the turnover of 7-14 C-nicotinamide dinucleotides in mice. 18 The metabolic reduction of acetylpyridines was investigated using CBRs derived from rabbit liver, 19 kidney, 20 and heart. 21 Additionally, reduction by the rat liver S-9 fraction was also reported, but the main enzyme catalyzing the reduction was not identified.…”

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confidence: 99%

Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines

et al. 2005

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Acetylpyridines (1-3) are known as aroma components of foods, perfumes, and smoking suppressants, showing several biological activities and constituting part of the structure of some important biologically active compounds. We purified and characterized an enzyme that catalyzes the stereoselective reduction of acetylpyridines so that we could clarify its function. The enzyme participating in the reductive metabolism of 4-acetylpyridine (1) in the rat liver was purified by successively applying ammonium sulfate fractionation, anion-exchange, gel filtration, and affinity chromatography, and it was definitively identified as 3alpha-HSD. It preferentially reduced acetylpyridines (1-3) and acetophenone (7) to their corresponding (S)-alcohols, with high enantioselectivity. Kinetic analyses of the compounds were performed, and the V(max)/K(m) values decreased in the order of 4-, 2-, and 3-acetylpyridine (1, 3, 2), while acetophenone (7) showed almost the same value as 3-acetylpyridine (2). These results suggested that the reduction of the substrates by 3alpha-HSD is affected by the nitrogen atom in the aromatic ring.

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“…1 These toxic chemicals have the ability to interact with bio-molecules physically and chemically. 2 This toxicant-bio-molecule interaction is not healthy in nature and leads to potential damages. 2 3 Due to the ability of potential interference by toxicants, 4 the possibility of inauspicious health effects in humans is commonly assessed by enzymatic biosensor.…”

Section: Introductionmentioning

confidence: 99%

Extended Bio-Analytical Approach for the Determination of Potential Toxicants

Nesakumar¹,

Krishnan²,

Sethuraman³

et al. 2015

j comput theor nanosci

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In the view of difficulties in finding the recovery and inhibition of an immobilized enzyme from the degree of inhibition, an equation based upon the degree of inhibition has been developed by considering incubation time at different time intervals. In this work, data of an enzymatic kinetic reaction at different incubation time intervals were used to exemplify practicability of the proposed equation in the field of enzyme-inhibition based electrochemical biosensor. For validation purpose, the results obtained from the extended bio-analytical approach were compared to the degree of inhibition and the results were found to be satisfactory. Using this extended bio-analytical technique, the degree of toxicity of environmental toxicants can be determined.

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Drug–Biomolecule Interactions: Drug Toxicity and Vitamin Coenzyme Depletion

Cited by 8 publications

References 26 publications

Final Report of the Safety Assessment of Niacinamide and Niacin1

Final Report of the Safety Assessment of Niacinamide and Niacin1

Purification and characterization of rat liver enzyme catalyzing stereoselective reduction of acetylpyridines

Extended Bio-Analytical Approach for the Determination of Potential Toxicants

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