Anandakumar P, Kamaraj S, Jagan S, Ramakrishnan G, Devaki T
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
Fundam Clin Pharmacol. 2009 Feb;23(1):97-103. doi: 10.1111/j.1472-8206.2008.00637.x. Epub 2009 Jan 10.
The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, beta-D-glucosidase, beta-D-galactosidase, beta-D-glucuronidase, beta-D-N-acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis.
本研究的目的是调查溶酶体是否是苯并(a)芘诱导的、氧化应激介导的瑞士白化小鼠肺癌的靶点，以及植物化学物质辣椒素在减轻溶酶体损伤中可能发挥的作用。基于羰基含量水平评估氧化应激。评估溶酶体蛋白酶如组织蛋白酶-D、组织蛋白酶-B、β-D-葡萄糖苷酶、β-D-半乳糖苷酶、β-D-葡萄糖醛酸酶、β-D-N-乙酰氨基葡萄糖苷酶和酸性磷酸酶的活性，以评估溶酶体功能。给小鼠施用苯并(a)芘（50毫克/千克体重）会导致溶酶体酶活性增加，羰基含量增加表明氧化应激明显。用辣椒素（10毫克/千克体重）处理可降低羰基含量，并使溶酶体酶活性恢复到接近正常水平。溶酶体的透射电子显微镜研究进一步显示了辣椒素对苯并(a)芘诱导的肺癌中溶酶体损伤的防御作用。从本研究可以得出结论，溶酶体损伤是苯并(a)芘诱导的肺癌中不可或缺的事件，辣椒素能够有效预防它，这证明了辣椒素对苯并(a)芘诱导的实验性肺癌的化学保护作用。
