Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. Methods: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. Results: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. Conclusions: The nephrotoxic potential of HM containing AA was similar to that of AA itself.
Abstract
Background/Aims: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. Methods: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. Results: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. Conclusions: The nephrotoxic potential of HM containing AA was similar to that of AA itself.
참고문헌 (15)
- Vanherweghem JL, "Rapidly progressive interstitial renal fibrosis in young women : association with slimming regimen including Chinese herbs", Lancet, 341, pp.387~391 (1993)
- Lord GM, "Nephropathy caused by Chinese herbs in the UK", Lancet, 354, pp.481~482 (1999)
- Lee S, "Fanconi’s syndrome and subsequent progressive renal failure caused by a Chinese herb containing aristolochic acid", Nephrology(Carlton), 9, pp.126~129 (2004)
- Yang L, "Aristolochic acid nephropathy : variation in presentation and prognosis", Nephrol Dial Transplant, 27, pp.292~298 (2012)
- Tian Y, "Expression of histone deacetylase-1 and p300 in aristolochic acid nephropathy models", Toxicol Mech Methods, 24, pp.377~384 (2014)
- Savransky V, "Role of the T-cell receptor in kidney ischemia-reperfusion injury", Kidney Int, 69, pp.233~238 (2006)
- Lim SW, "Oral administration of ginseng ameliorates cyclosporine-induced pancreatic injury in an experimental mouse model", PLoS One, 8, pp.e72685~ (2013)
- Wu J, "Bardoxolone methyl(BARD)ameliorates aristolochic acid(AA)-induced acute kidney injury through Nrf2 pathway", Toxicology, 318, pp.22~31 (2014)
- Decleves AE, "Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury : an old friend with new assets", Exp Physiol, 101, pp.193~206 (2016)
- Dai XY, "Smad7 protects against chronic aristolochic acid nephropathy in mice", Oncotarget, 6, pp.11930~11944 (2015)
- Zhao YY, "Metabolomics analysis reveals the association between lipid abnormalities and oxidative stress, inflammation, fibrosis, and Nrf2 dysfunction in aristolochic acid-induced nephropathy", Sci Rep, 5, pp.12936~ (2015)
- 반태현, "Update of aristolochic acid nephropathy in Korea", The Korean Journal of Internal Medicine, 33(5), pp.961~969 (2018), 대한내과학회[DOI]
- Matsui K, "Renal liver-type fatty acid binding protein(L-FABP)attenuates acute kidney injury in aristolochic acid nephrotoxicity", Am J Pathol, 178, pp.1021~1032 (2011)
- Zeng Y, "Autophagy inhibitors promoted aristolochic acid I induced renal tubular epithelial cell apoptosis via mitochondrial pathway but alleviated nonapoptotic cell death in mouse acute aritolochic acid nephropathy model", Apoptosis, 19, pp.1215~1224 (2014)
- Huljic S, "Species-specific toxicity of aristolochic acid(AA)in vitro", Toxicol In Vitro, 22, pp.1213~1221 (2008)