Objective： （＋）-Clausenamide （（＋）-CLA）, the active ingredient of wampee, was isolated from the leaves of Clausena lansium （Lour.） Skeels. This study aimed to evaluate the protective potential of ...Objective： （＋）-Clausenamide （（＋）-CLA）, the active ingredient of wampee, was isolated from the leaves of Clausena lansium （Lour.） Skeels. This study aimed to evaluate the protective potential of （＋）-CLA against acetaminophen （APAP）-induced nephrotoxicity in mice. Methods： Mice were divided into control, APAP, high-dose （＋）-CLA, and low-dose （＋）-CLA groups. Then, mice were preadministered （＋）-CLA （50 and 100 mg/kg） for 5 consecutive days. After the last treatment, the animals received a single intraperitoneal injection of APAP （600 mg/kg）. Renal histopathology was evaluated by staining with hematoxylin and eosin. The levels of malondialdehyde （MDA） and glutathione （GSH） and the activities of catalase （CAT） and superoxide dismutase （SOD） were determined using corresponding kits. Western blotting was used to analyze the expression of apoptosis-related proteins in renal tissue. Results： Administration of APAP increased serum creatinine and blood urea nitrogen levels in comparison with the control group. An increase in renal MDA level, depletion of GSH, and reductions in CAT and SOD activities in renal tissue indicated that APAP-induced kidney injury was mediated by oxidative stress. The expressions of Bax and caspase-3, cleavage of caspase-3, and cytoplasm cytochrome c levels were up-regulated in renal tissue, whereas Bcl-2 expression and mitochondrial cytochrome c levels were down-regulated in the APAP group, which revealed that APAP-induced kidney injury significantly increased cell apoptosis in renal tubules. The histopathology of kidney tissue supported these biochemical mechanisms. （＋）-CLA can reverse changes in most of the abovementioned parameters and nearly restore the normal structure of the kidney. Conclusion： Oxidative stress and apoptosis are considered to be the mechanisms underlying APAP-induced nephrotoxicity. （＋）-CLA could be a promising antidote for APAP-induced acute renal damage owing to its antioxidative and antiapoptotic effects.展开更多
基金This work was partly supported by TCM Modernization Program of Hainan Province （2015ZY01）, Natural Science Foundation of China （81573675 ＆ 81622050 ＆ 81673709）, Science and Technology Program of Guangzhou （201604046016 ＆ 201604020175） and Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine （20161070）.
文摘Objective： （＋）-Clausenamide （（＋）-CLA）, the active ingredient of wampee, was isolated from the leaves of Clausena lansium （Lour.） Skeels. This study aimed to evaluate the protective potential of （＋）-CLA against acetaminophen （APAP）-induced nephrotoxicity in mice. Methods： Mice were divided into control, APAP, high-dose （＋）-CLA, and low-dose （＋）-CLA groups. Then, mice were preadministered （＋）-CLA （50 and 100 mg/kg） for 5 consecutive days. After the last treatment, the animals received a single intraperitoneal injection of APAP （600 mg/kg）. Renal histopathology was evaluated by staining with hematoxylin and eosin. The levels of malondialdehyde （MDA） and glutathione （GSH） and the activities of catalase （CAT） and superoxide dismutase （SOD） were determined using corresponding kits. Western blotting was used to analyze the expression of apoptosis-related proteins in renal tissue. Results： Administration of APAP increased serum creatinine and blood urea nitrogen levels in comparison with the control group. An increase in renal MDA level, depletion of GSH, and reductions in CAT and SOD activities in renal tissue indicated that APAP-induced kidney injury was mediated by oxidative stress. The expressions of Bax and caspase-3, cleavage of caspase-3, and cytoplasm cytochrome c levels were up-regulated in renal tissue, whereas Bcl-2 expression and mitochondrial cytochrome c levels were down-regulated in the APAP group, which revealed that APAP-induced kidney injury significantly increased cell apoptosis in renal tubules. The histopathology of kidney tissue supported these biochemical mechanisms. （＋）-CLA can reverse changes in most of the abovementioned parameters and nearly restore the normal structure of the kidney. Conclusion： Oxidative stress and apoptosis are considered to be the mechanisms underlying APAP-induced nephrotoxicity. （＋）-CLA could be a promising antidote for APAP-induced acute renal damage owing to its antioxidative and antiapoptotic effects.
