Drug and Chemical Toxicology ( IF 2.6 ) Pub Date : 2020-08-05 , DOI: 10.1080/01480545.2020.1802478 Akinleye S Akinrinde 1 , Kehinde O Soetan 1 , Monsuru O Tijani 2
Abstract
NSAID-induced gastrointestinal toxicity is associated with non-selective inhibition of cyclooxygenase (COX)-mediated synthesis of prostaglandins. Fluoride salts, known to stimulate COX-2 synthesis, have also been associated with gastrointestinal damage. The effects of fluoride treatment on NSAID toxicity are, however, yet to be clarified. This study examined the effect of sodium fluoride (NaF) on diclofenac (DIC)-induced gastroduodenal and hepatic toxicity in rats. In addition, the potential protective role of Luteolin (Lut), an antioxidant and anti-inflammatory flavonoid, in co-exposure to NaF and DIC was also investigated. Five groups of rats were treated thus: Group A (control): distilled water vehicle for 8 days; Group B: DIC (9 mg/kg) orally, twice daily from days 6 to 8; Group C: NaF (300 ppm) plus DIC for the final 3 days; Groups D and E: Luteolin at 100 mg/kg and 200 mg/kg, respectively, with concurrent NaF and DIC exposures. Rats co-treated with DIC and NaF exhibited the highest severity of dark watery diarrhea and gastroduodenal hemorrhages. NaF aggravated the DIC-induced increases in malondialdehyde (MDA), advanced oxidation protein products (AOPP), protein carbonyls (PC), H2O2, and nitric oxide, while inhibiting glutathione peroxidase (GPx) and glutathione S-transferase (GST) in all the tissues. In contrast, Luteolin treatment significantly attenuated the gastroduodenal and hepatic damage caused by NaF and DIC co-administration by suppressing oxidative damage and lesions in the tissues. These results show, for the first time, that NaF may enhance diclofenac-induced gastrointestinal toxicity and also suggest that Luteolin may be a promising lead for the treatment of drug-induced gastroenteropathy.
中文翻译:
大鼠同时暴露于氟化钠会加重双氯芬酸引起的胃肠肝损伤:木犀草素的保护作用
摘要
NSAID 诱导的胃肠道毒性与环氧合酶 (COX) 介导的前列腺素合成的非选择性抑制有关。已知可刺激 COX-2 合成的氟化物盐也与胃肠道损伤有关。然而,氟化物治疗对 NSAID 毒性的影响尚待阐明。本研究检查了氟化钠 (NaF) 对双氯芬酸 (DIC) 诱导的大鼠胃十二指肠和肝脏毒性的影响。此外,还研究了木犀草素 (Lut)(一种抗氧化剂和抗炎类黄酮)在共同暴露于 NaF 和 DIC 时的潜在保护作用。如此处理五组大鼠: A组(对照):蒸馏水载体8天;B 组:DIC (9 mg/kg) 口服,从第 6 天到第 8 天每天两次;C 组:最后 3 天的 NaF (300 ppm) 加 DIC;D组和E组:木犀草素分别为 100 mg/kg 和 200 mg/kg,同时暴露于 NaF 和 DIC。用 DIC 和 NaF 共同治疗的大鼠表现出最严重的深色水样腹泻和胃十二指肠出血。NaF 加剧了 DIC 诱导的丙二醛 (MDA)、高级氧化蛋白产物 (AOPP)、蛋白质羰基化合物 (PC)、H2 O 2和一氧化氮,同时抑制所有组织中的谷胱甘肽过氧化物酶 (GPx) 和谷胱甘肽 S-转移酶 (GST)。相比之下,木犀草素治疗通过抑制组织中的氧化损伤和病变,显着减轻了 NaF 和 DIC 共同给药引起的胃十二指肠和肝脏损伤。这些结果首次表明,NaF 可能会增强双氯芬酸引起的胃肠道毒性,并且还表明木犀草素可能是治疗药物引起的胃肠病的有希望的先导药物。