Chakraborty Santanu, Kar Sudip Kumar, Roy Kunal, Sengupta Chandana
Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700 032, India.
Acta Pol Pharm. 2006 Mar-Apr;63(2):83-8.
As a part of our ongoing effort to explore drug induced lipid peroxidation in relation to drug-induced toxicity, this study was undertaken to determine whether nonsteroidal anti-inflammatory drugs (NSAIDs), namely, diclofenac sodium, ibuprofen, flurbiprofen, paracetamol, nimesulide, celecoxib and indomethacin are involved in oxidative/antioxidative processes by determining malondialdehyde (MDA) concentration as an index of lipid peroxidation. Considering lipid peroxidation, a possible mediator of toxicity, an attempt was made to see the suppressive action of ascorbic acid, a conventional antioxidant compound, on NSAID-induced lipid peroxidation. It was found that diclofenac sodium, ibuprofen, flurbiprofen and paracetamol exerted statistically significant decrease of MDA content, suggesting a potential of the molecules to suppress the lipid peroxidation. At earlier stage of incubation nimesulide shows statistically significant decrease of MDA content followed by lipid peroxidation induction at the later stage of incubation period, suggesting involvement of nimesulide in antioxidative/oxidative processes. Celecoxib and indomethacin both exerted statistically significant increase of MDA content, representing significant peroxidation activity. Ascorbic acid, a promising antioxidant, could significantly reduce celecoxib and indomethacin induced lipid peroxidation.
作为我们探索药物诱导的脂质过氧化与药物诱导毒性之间关系的持续努力的一部分,本研究旨在通过测定丙二醛(MDA)浓度作为脂质过氧化指标,来确定非甾体抗炎药(NSAIDs),即双氯芬酸钠、布洛芬、氟比洛芬、对乙酰氨基酚、尼美舒利、塞来昔布和吲哚美辛是否参与氧化/抗氧化过程。考虑到脂质过氧化可能是毒性的一种介导因素,我们尝试观察传统抗氧化化合物抗坏血酸对NSAIDs诱导的脂质过氧化的抑制作用。结果发现,双氯芬酸钠、布洛芬、氟比洛芬和对乙酰氨基酚使MDA含量在统计学上显著降低,表明这些分子具有抑制脂质过氧化的潜力。在孵育早期,尼美舒利使MDA含量在统计学上显著降低,而在孵育后期则诱导脂质过氧化,这表明尼美舒利参与了抗氧化/氧化过程。塞来昔布和吲哚美辛均使MDA含量在统计学上显著增加,表现出显著的过氧化活性。有前景的抗氧化剂抗坏血酸能够显著降低塞来昔布和吲哚美辛诱导的脂质过氧化。