Dakshayani K B, Subramanian P, Manivasagam T, Mohamed Essa M
Department of Biochemistry, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
Fundam Clin Pharmacol. 2006 Oct;20(5):477-80. doi: 10.1111/j.1472-8206.2006.00422.x.
Chemoprevention of cancer is one of the reliable approaches to control the incidence of cancer. In the present study, we investigated the chemopreventive role of alpha-ketoglutarate (alpha-KG) during N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. The activities of serum aspartate and alanine transaminases were found to be significantly higher in NDEA + CCl(4)-treated animals when compared with control animals. Administration of alpha-KG restored the activities of transaminases to near normal range. The levels of lipid peroxides, thiobarbituric acid reactive substances were decreased in the liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG reversed the lipid peroxide levels to near normal range. Levels of antioxidants, reduced glutathione and activities of its dependent enzymes, glutathione peroxidase and glutathione-S-transferase were found to be significantly higher in liver tissue of NDEA + CCl(4)-treated animals when compared with control animals. alpha-KG administration positively modulated the antioxidant levels to near normal range. In conclusion, it can be suggested that alpha-KG exerts chemopreventive role which may attributable to its ability to positively modulate the transaminase activities and oxidant-antioxidant imbalance during hepatocarcinogenesis.
癌症的化学预防是控制癌症发病率的可靠方法之一。在本研究中，我们调查了α-酮戊二酸（α-KG）在N-亚硝基二乙胺（NDEA）诱导的肝癌发生过程中的化学预防作用。与对照动物相比，发现NDEA + CCl₄处理的动物血清天冬氨酸和丙氨酸转氨酶的活性显著更高。给予α-KG可使转氨酶活性恢复到接近正常范围。与对照动物相比，NDEA + CCl₄处理的动物肝脏组织中脂质过氧化物、硫代巴比妥酸反应性物质的水平降低。α-KG使脂质过氧化物水平恢复到接近正常范围。与对照动物相比，发现NDEA + CCl₄处理的动物肝脏组织中抗氧化剂、还原型谷胱甘肽的水平及其相关酶谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶的活性显著更高。给予α-KG可使抗氧化剂水平正向调节至接近正常范围。总之，可以认为α-KG发挥化学预防作用，这可能归因于其在肝癌发生过程中正向调节转氨酶活性和氧化-抗氧化失衡的能力。
