Kumral A, Giriş M, Soluk-Tekkeşin M, Olgaç V, Doğru-Abbasoğlu S, Türkoğlu Ü, Uysal M
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
Hum Exp Toxicol. 2016 Jun;35(6):635-43. doi: 10.1177/0960327115597468. Epub 2015 Jul 29.
Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats.
Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities.
DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues.
Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes.
氧化应激在阿霉素（DOX）诱导的毒性中起重要作用。肌肽（CAR）是一种具有抗氧化特性的二肽。本研究旨在评估单独使用CAR或与维生素E联合使用（CAR + 维生素E）对DOX诱导的大鼠心脏、肝脏和脑毒性的减轻或预防作用。
大鼠连续12天接受CAR（250 mg kg⁻¹ 天⁻¹；腹腔注射（i.p.））或CAR + 维生素E（相当于200 mg kg⁻¹ α-生育酚；每3天一次；肌肉注射）治疗。在治疗的第8天，大鼠单次注射一剂DOX（30 mg kg⁻¹，i.p.）。测量血清心肌肌钙蛋白I（cTnI）、尿素和肌酐水平；丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性；以及组织中的氧化应激参数。我们还测定了硫代巴比妥酸反应性物质、二烯共轭物、蛋白质羰基（PC）和谷胱甘肽水平以及抗氧化酶活性。
DOX导致血清cTnI、ALT、AST、尿素和肌酐水平升高，组织中脂质过氧化物和PC水平升高。CAR或CAR + 维生素E治疗导致血清cTnI水平以及ALT和AST活性降低。这些治疗降低了促氧化状态，并改善了所检查组织的组织病理学结果。
我们的结果可能表明，单独使用CAR，尤其是与维生素E联合使用，可保护大鼠心脏、肝脏和肾脏组织免受DOX诱导的毒性。这通过改善心脏、肝脏和肾脏标志物以及恢复促氧化状态和改善组织病理学变化得到证明。
