Codeine induced hematological, hepatic alterations, lung and brain damage in mice

Adele Bernard Omokheshi, Alonge Adeyinka Joseph, Adewoye Elsie Olufunke
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Abstract

Codeine, an opiate derivate, which induces pleasure and euphoria in users, is contained in many OTC cough syrups as dextromethorphan. In 2011, its abuse has been reported in Nigeria from consumption of codeine-based cough syrup such as Benylin containing codeine syrup (BCS). Thereafter, the neurobehavioural alteration was reported with BCS in mice. 45 Swiss male mice (20 g -25 g) were grouped into control, low dose-(10.95 ml/kg BCS) and High dose-(21.90 ml/kg of BCS). BCS was given orally above the therapeutic dose for 4weeks. Blood samples were collected after 7 and 28days under mild ether anesthesia into plain and heparinized bottles to assess hematological indices, serum creatinine level, and activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Thereafter, the brain, lung, and liver were excised and processed for brain protein level and histopathological observation. Data were analyzed using Two-way ANOVA at P < 0.05. At both doses, BCS reduced hemoglobin concentration (10.56; 21.69%), lymphocyte count (10.54; 29.22%) and brain protein level (4.86±0.81; 4.86 ± 0.80 vs 9.20 ± 0.61 g/l) while white blood cell count (20.47; 46.08%), serum creatinine level (5.36; 18.75%), AST (26.31; 32.77%) and ALT (22.90; 36.70%) activities were increased compared to control. Histology shows marked necrosis and chronic infiltration by inflammatory cells in the brain, liver, and lung. Acute and chronic treatment of mice with Benylin with codeine resulted in significant alterations in blood and vital body organs such as kidney, liver, lung, and brain in a dose-dependent manner.
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可待因引起小鼠血液学、肝脏改变、肺和脑损伤
可待因是一种鸦片衍生物,能使服用者产生愉悦感和欣快感,在许多非处方止咳糖浆中以右美沙芬的形式存在。2011年,据报告,尼日利亚因食用含有可待因糖浆的Benylin等含可待因糖浆的可待因止咳糖浆而滥用可待因。此后,BCS小鼠的神经行为改变被报道。将45只瑞士雄性小鼠(20 g ~ 25 g)分为对照组、低剂量组(10.95 ml/kg BCS)和高剂量组(21.90 ml/kg BCS)。BCS在治疗剂量以上口服4周。分别于轻度乙醚麻醉7天和28d后取血,分别装于普通瓶和肝素化瓶中,测定血液学指标、血清肌酐水平、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性。随后,切除大鼠脑、肺、肝,进行脑蛋白水平和组织病理学观察。数据分析采用双因素方差分析,P < 0.05。在两个剂量下,BCS降低血红蛋白浓度(10.56;21.69%),淋巴细胞计数(10.54;29.22%)和脑蛋白水平(4.86±0.81;4.86±0.80 vs 9.20±0.61 g/l),白细胞计数(20.47;46.08%),血清肌酐水平(5.36;18.75%), ast (26.31;32.77%)和ALT (22.90;36.70%)活性较对照组增加。组织学显示脑、肝、肺有明显的坏死和慢性炎症细胞浸润。用Benylin和可待因对小鼠进行急性和慢性治疗,导致血液和重要身体器官如肾、肝、肺和脑的显著改变,并呈剂量依赖性。
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