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首页> 外文期刊>The Internet Journal of Toxicology >Sperm head abnormality and mutagenic effects of aspirin, paracetamol and caffeine containing analgesics in rats
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Sperm head abnormality and mutagenic effects of aspirin, paracetamol and caffeine containing analgesics in rats

机译：阿司匹林，扑热息痛和含咖啡因的镇痛药对大鼠精子畸形及致突变作用

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The mutagenic effects of analgesics with aspirin, paracetamol and caffeine combinations were evaluated in a male rat model using a short-term in vivo mutagenicity test (sperm head abnormality assay). A 90-day exposure to recommended doses of the five analgesics, Aspirin (aspirin only), Cafenol (aspirin + caffeine), Panadol (paracetamol only), Pentax (paracetamol + caffeine) and Daga+ (aspirin + paracetamol + caffeine), significantly (P<0.001) increased sperm head abnormality compared with controls; this exposure time also increased mutagenicity (or mutation indices) by at least 1.67-fold. The presence of caffeine in both Cafenol and Pentax analgesics reduced mutagenicity, while the presence of caffeine in Daga+ had a synergistic effect that significantly increased both the frequency of abnormal sperm heads to 13.5% and the mutation index to 8.00. Sperm head abnormality was also proportional to mutation index Introduction Analgesics with aspirin, paracetamol and caffeine combinations are ingested for many reasons including: general pains, headaches, fevers, cold, flu, rheumatoid arthritis, circulation problems (1) and in cases of dependent-addiction (2). In recent years, there has been an increasing awareness and realization of the genotoxic potentials of a wide variety of drugs, food additives, environmental pollutants (3, 4) and other socially acceptable compounds such as aspirin and caffeine (5). Habitual ingestion of aspirin and caffeine has been shown to be capable of inducing structural chromosomal aberrations in somatic cells in vivo (6) and reproductive toxicology (5). This awareness follows the recent development of appropriate, sensitive and practical methods for detecting and estimating the toxic effects of these substances and their impact on environmental health.Aspirin is one of the most widely used analgesics available without prescription in several parts of the world (7). Mutagenic studies of aspirin in mammals are not common and are mostly limited to in vitro experiments. Kimmel et al. (8), reported the teratogenic effects of aspirin in Wister rats resulting in malformations of limbs, while Jones and Bodmer (3) suggested similar effects in humans at recommended doses. It has been identified as a behavioural teratogen in humans at doses too low to produce differential birth-weight effects (6); and it has also been reported that maternal aspirin use during the first-half of the pregnancy has a high significant effect (P<0.0005) on intelligence quotient (IQ) and attention in exposed children (9). There are conflicting reports on potentials of paracetamol as an experimental carcinogenic agent, although evidences implicate metabolites of paracetamol and phenacetin as being active experimental carcinogenic agents (2, 10, 11). Paracetamol has also been reported to inhibit DNA synthesis by 70-90% at 1hour following an oral dose in the spleen, testis, thymus, stomach, small intestine and bone marrow (12).Caffeine is often used with aspirin and paracetamol to augment their antipyretic and analgesic effects (13). There is a strong relationship between the ingestion of various combinations of analgesics with caffeine resulting in approximately 2-fold increase in the risk of cancers of the pelvic, kidney, bladder and urinary tract (2, 11). In view of such findings, this study set out to further explore the effect of caffeine on the mutagenicity of analgesics with aspirin, paracetamol and caffeine combinations in rats as model using short-term in vivo mutagenicity assay to assess their effects on sperm head abnormality and mutation index. Materials and methods Forty-eight healthy isogenic strains of male albino rats (Rattus norvegicus) of about ten to eleven weeks old were obtained from the rat colony of the Department of Zoology and Environmental Biology, University of Calabar, Calabar-Nigeria for the study. The rats were housed in conventional cages and maintained under standard laboratory conditions in the animal house a
机译：使用短期体内致突变性试验（精子头部异常试验），在雄性大鼠模型中评估了阿司匹林，扑热息痛和咖啡因组合镇痛药的致突变作用。 90天的推荐剂量的五种镇痛药阿司匹林（仅阿司匹林），咖啡酚（阿司匹林+咖啡因），帕那多（仅扑热息痛），宾得（对乙酰氨基酚+咖啡因）和Daga +（阿司匹林+扑热息痛+咖啡因）推荐剂量为90天（ P <0.001）与对照组相比，精子头异常增加;这种暴露时间也将诱变性（或突变指数）提高了至少1.67倍。 Cafenol和Pentax镇痛药中都存在咖啡因会降低致突变性，而Daga +中咖啡因的存在会产生协同作用，使异常精子的出现频率显着提高至13.5％，突变指数提高至8.00。精子头异常也与突变指数成正比。简介服用具有阿司匹林，扑热息痛和咖啡因组合的镇痛药的原因很多，包括：全身疼痛，头痛，发烧，感冒，流感，类风湿性关节炎，血液循环问题（1）以及在依赖的情况下-成瘾（2）。近年来，人们对各种各样的药物，食品添加剂，环境污染物（3、4）和其他社会可接受的化合物（例如阿司匹林和咖啡因）（5）的遗传毒性潜力有了越来越高的认识和认识。习惯摄入阿司匹林和咖啡因已被证明能够在体内体细胞中诱导结构性染色体畸变（6）和生殖毒理学（5）。这种认识是由于最近开发出了适当，敏感和实用的方法来检测和评估这些物质的毒性作用及其对环境健康的影响。阿司匹林是世界上最广泛使用的无处方镇痛药之一（7 ）。阿司匹林在哺乳动物中的诱变研究并不常见，并且主要限于体外实验。 Kimmel等。 （8）报告了阿司匹林对Wister大鼠的致畸作用，导致肢体畸形，而Jones和Bodmer（3）建议以推荐剂量对人产生类似作用。它已被确认为人类行为性致畸物，剂量太低而无法产生不同的出生体重效应（6）;并且也有报道说，孕妇在怀孕的上半年使用阿司匹林对暴露于儿童的智商（IQ）和注意力有很高的显着影响（P <0.0005）（9）。关于扑热息痛作为实验性致癌剂的潜力有相互矛盾的报道，尽管有证据表明扑热息痛和非那西丁的代谢产物是有效的实验性致癌剂（2、10、11）。据报道，对乙酰氨基酚在脾脏，睾丸，胸腺，胃，小肠和骨髓中口服后1小时可抑制DNA合成70-90％（12）。咖啡因经常与阿司匹林和扑热息痛一起使用以增加其解热和镇痛作用（13）。摄入止痛药和咖啡因的各种组合之间存在密切关系，导致盆腔，肾脏，膀胱和泌尿道癌症的风险增加约2倍（2、11）。鉴于这些发现，本研究着手使用短期体内致突变性试验评估咖啡因对大鼠阿司匹林，扑热息痛和咖啡因组合的镇痛药致突变性的作用，以评估其对精子头异常和突变指数。材料与方法从卡拉巴尔－尼日利亚卡拉巴尔大学动物与环境生物学系的鼠群中获得约10至11周龄的48只健康的雄性白化鼠（Rattus norvegicus）同基因株。将大鼠饲养在常规笼中，并在标准实验室条件下饲养在动物房中。

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