In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury

Venkatesan, Narayanan; Chandrakasan, Gowri

doi:10.1016/0926-6917(94)90028-0

Cited by 14 publications

(8 citation statements)

References 34 publications

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“…The parent drug is released in vivo by biological or chemical degradation of the prodrug. We have shown that nicotinates are promising prodrugs of nicotinic acid (Hsu et al, 2003), a precursor of NAD + (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate), that is under investigation for the prevention of skin carcinogenesis and has been proven beneficial against bleomycin-and cyclophosphamide-induced lung injury (Gurujeyalakshmi et al, 2000a, b;Venkatesan and Chandrakasan, 1994). Specifically, nicotinates are significantly soluble in PFOB and, depending on their chemical structure, release the parent drug nicotinic acid by both chemical and enzymatic hydrolysis with half-life's ranging from a few minutes to several weeks (Hsu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, physicochemical properties and in vitro cytotoxicity of nicotinic acid ester prodrugs intended for pulmonary delivery using perfluorooctyl bromide as vehicle

Lehmler

Vyas

et al. 2008

International Journal of Pharmaceutics

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This study explores perfluorooctyl bromide (PFOB) as a potential vehicle for the pulmonary delivery of a series of prodrugs of nicotinic acid using cell culture studies. The prodrugs investigated have PFOB-water (log K p = 0.78 to > 2.2), perfluoromethylcyclohexane-toluene (log K p = −2.62 to 0.13) and octanol-water (log K p = 0.90 to 10.2) partition coefficients spanning several orders of magnitude. In confluent NCI-358 human lung cancer cells, the toxicity of prodrugs administered in culture medium or PFOB depends on the medium of administration, with EC20's above 8 mM and 2.5 mM for culture medium and PFOB, respectively. Short-chain nicotinates administered both in PFOB and medium increase cellular NAD/NADP levels at 1 mM nicotinate concentrations. Long-chain nicotinates, which could not be administered in medium due to their poor aqueous solubility, increased NAD/NADP levels if administered in PFOB at concentrations ≥ 10 mM. These findings suggest that even highly lipophilic prodrugs can partition out of the PFOB phase into cells, where nicotinic acid is released and converted to NAD. Thus, PFOB may be a novel and biocompatible vehicle for the delivery of lipophilic prodrugs of nicotinic acid and other drugs directly to the lung of laboratory animals and humans.

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Section: Introductionmentioning

confidence: 99%

Synthesis, physicochemical properties and in vitro cytotoxicity of nicotinic acid ester prodrugs intended for pulmonary delivery using perfluorooctyl bromide as vehicle

Lehmler

Vyas

et al. 2008

International Journal of Pharmaceutics

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“…Numerous studies, conducted on a variety of biological samples and under in vitro and in vivo conditions, have verified that TAU, in spite of a lack of ready oxidizibility, can express antioxidant actions such as serving as a trap for hypochlorous acid (HOCl) 51,59 , decreasing the formation of , inhibiting the malondialdehyde 25,32,53 and of reactive oxygen species depletion of natural anti-oxidants , minimizing oxidant-mediated protein and ATPase activity losses 6 (Banks et al, 1992), and reversing the decrease in antioxidant enzyme activities under oxidative stress . As a result of these actions, TAU may contribute to the maintenance of cell viability 1,6,33 , the modulation of cell necrosis and apoptosis 38,56 , the attenuation of cell damage 21,31,42,55 , and the curtailment of tissue fibrosis 21,53 . The purpose of the present investigation was to examine the effects of TAU against oxidative cell injury using a simple and reproducible in vitro test system and a readily available model oxidant 48 .…”

Section: Introductionmentioning

confidence: 99%

Protection by Taurine and Structurally Related Sulfur-Containing Compounds Against Erythrocyte Membrane Damage by Hydrogen Peroxide

Pokhrel

Lau‐Cam

2002

Advances in Experimental Medicine and Biology

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“…Besides being the precursor of cofactors to many vital enzymes, nicotinic acid is a drug possessing vasodilating and fibrinolytic properties. Nicotinic acid itself has been proven beneficial against bleomycin-and cyclophosphamide-induced lung injury in animal models (1)(2)(3)(4)(5). Dietary supplements of nicotinic acid and dermatologic formulations of its longchain esters are under investigation for the prevention and treatment of skin carcinogenesis (6).…”

mentioning

confidence: 99%

Interaction of long-chain nicotinates with dipalmitoylphosphatidylcholine

Lehmler

Fortis-Santiago

Nauduri

et al. 2005

Journal of Lipid Research

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The interaction of four long-chain nicotinates, compounds that are of interest as potential chemopreventive agents, with dipalmitoylphosphatidylcholine (DPPC) was investigated in monolayers at the air-water interface and in fully hydrated bilayers. For the monolayer studies, the compression isotherms of mixtures of the respective nicotinate with DPPC were recorded at various compositions on a hydrochloric acid subphase (pH 1.9-2.1, 37 ؎ 2 ؇ C). The headgroup of the nicotinates (24-29 Å 2 /molecule) is larger than that of the hydrophobic tail (20 Å 2 /molecule). The pure nicotinates exhibit a temperature-and chain lengthdependent transition from an expanded to a condensed phase. Analysis of the concentration dependence of the average molecular area at constant film pressure and the concentration dependence of the breakpoint of the phase transition from the expanded to the condensed state suggests that all four DPPC-nicotinate mixtures are partially miscible at the air-water interface. Although a complex phase behavior with several phase transitions was observed, differential scanning calorimetry studies of the four mixtures are also indicative of the partial miscibility of DPPC and the respective nicotinate.Overall, the complex phase behavior most likely results from the head-tail mismatch of the nicotinates and the geometric packing constraints in the twocomponent lipid bilayer. Nicotinic acid and its alkyl esters are of considerable biological and pharmacological importance. Besides being the precursor of cofactors to many vital enzymes, nicotinic acid is a drug possessing vasodilating and fibrinolytic properties. Nicotinic acid itself has been proven beneficial against bleomycin-and cyclophosphamide-induced lung injury in animal models (1-5). Dietary supplements of nicotinic acid and dermatologic formulations of its longchain esters are under investigation for the prevention and treatment of skin carcinogenesis (6). Therefore, nicotinic acid esters may be useful as a chemopreventive agent for the prevention of lung cancer.Currently, there is significant interest in the pulmonary administration of several chemopreventive agents, such as steroids and retinoids, directly to the lung because of reduced systemic toxicity (7-11). This route of administration may also be advantageous for the administration of nicotinic acid esters, by using either an aerosol or a perfluorocarbon vehicle (12, 13). Although the interaction of various chemopreventive agents, especially retinoids, with phospholipids has been investigated (14, 15), there is no current knowledge about the factors that determine the interaction (i.e., phase behavior) of nicotinates with biological lipids such as the phospholipids present in pulmonary surfactant. A better understanding of these interactions, however, is a prerequisite for the rational design of nicotinates for pulmonary administration, especially using a perfluorocarbon-based drug delivery system (12, 13). The aim of this study is to understand which molecular characteristics influe...

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In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury

Cited by 14 publications

References 34 publications

Synthesis, physicochemical properties and in vitro cytotoxicity of nicotinic acid ester prodrugs intended for pulmonary delivery using perfluorooctyl bromide as vehicle

Synthesis, physicochemical properties and in vitro cytotoxicity of nicotinic acid ester prodrugs intended for pulmonary delivery using perfluorooctyl bromide as vehicle

Protection by Taurine and Structurally Related Sulfur-Containing Compounds Against Erythrocyte Membrane Damage by Hydrogen Peroxide

Interaction of long-chain nicotinates with dipalmitoylphosphatidylcholine

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