Ko Je-Won, Shin Jin-Young, Kim Jeong-Won, Park Sung-Hyeuk, Shin Na-Rae, Lee In-Chul, Shin In-Sik, Moon Changjong, Kim Sung-Ho, Kim Sung-Hwan, Kim Jong-Choon
College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea; Ministry of Food and Drug Safety, Cheongju 28159, Republic of Korea.
Food Chem Toxicol. 2017 Apr;102:156-165. doi: 10.1016/j.fct.2017.02.021. Epub 2017 Feb 17.
Diallyl disulfide (DADS) is a degradation product of allicin which is contained in garlic. This study investigated the protective effects of DADS against acetaminophen (AAP)-induced nephrotoxicity and the molecular mechanisms of nephroprotective effects in rats. AAP caused severe nephrotoxicity as evidenced by significant increases in renal tubular cell apoptosis, mitochondria-mediated apoptosis, and up-regulation of nuclear transcription factor kappa-B (NF-κB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-α (TNF-α) in the kidney with histopathological alterations. After AAP administration, glutathione content and activities of catalase, superoxide dismutase, and glutathione reductase were significantly decreased whereas malondialdehyde content was significantly increased, indicating that AAP-induced kidney injury was mediated through oxidative stress. In contrast, DADS pretreatment significantly attenuated AAP-induced nephrotoxic effects, including oxidative damage, histopathological lesions, and apoptotic changes in the kidney. DADS also attenuated AAP-induced up-regulation of NF-κB, Cox-2, and TNF-α in the kidney, and microsomal CYP2E1 expression in liver and kidney. These results indicated that DADS could prevent AAP-induced nephrotoxicity. The protective effects of DADS might be due to its ability to decrease metabolic activation of AAP by inhibiting CYP2E1 and its potent antioxidant, antiapoptotic, and antiinflammatory effects via inhibition of NF-κB.
二烯丙基二硫化物（DADS）是大蒜中所含大蒜素的降解产物。本研究调查了DADS对大鼠扑热息痛（AAP）诱导的肾毒性的保护作用及其肾保护作用的分子机制。AAP导致严重的肾毒性，表现为肾小管细胞凋亡、线粒体介导的凋亡显著增加，以及肾脏中核转录因子κB（NF-κB）、环氧合酶-2（Cox-2）和肿瘤坏死因子-α（TNF-α）上调，并伴有组织病理学改变。给予AAP后，谷胱甘肽含量以及过氧化氢酶、超氧化物歧化酶和谷胱甘肽还原酶的活性显著降低，而丙二醛含量显著增加，表明AAP诱导的肾损伤是通过氧化应激介导的。相比之下，DADS预处理显著减轻了AAP诱导的肾毒性作用，包括氧化损伤、组织病理学病变和肾脏中的凋亡变化。DADS还减轻了AAP诱导的肾脏中NF-κB、Cox-2和TNF-α的上调，以及肝脏和肾脏中微粒体CYP2E1的表达。这些结果表明DADS可以预防AAP诱导的肾毒性。DADS的保护作用可能归因于其通过抑制CYP2E1降低AAP代谢活化的能力，以及其通过抑制NF-κB产生的强大抗氧化、抗凋亡和抗炎作用。
