PMID- 28219698 OWN - NLM STAT- MEDLINE DCOM- 20170327 LR - 20170327 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 102 DP - 2017 Apr TI - Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-kappaB. PG - 156-165 LID - S0278-6915(17)30067-4 [pii] LID - 10.1016/j.fct.2017.02.021 [doi] AB - 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-kappaB), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-alpha) 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-kappaB, Cox-2, and TNF-alpha 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-kappaB. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Ko, Je-Won AU - Ko JW AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Shin, Jin-Young AU - Shin JY AD - 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. FAU - Kim, Jeong-Won AU - Kim JW AD - Department of Food and Nutrition, Duksung Women's University, Seoul 01369, Republic of Korea. FAU - Park, Sung-Hyeuk AU - Park SH AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Shin, Na-Rae AU - Shin NR AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Lee, In-Chul AU - Lee IC AD - Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea. FAU - Shin, In-Sik AU - Shin IS AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Moon, Changjong AU - Moon C AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Kim, Sung-Ho AU - Kim SH AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. FAU - Kim, Sung-Hwan AU - Kim SH AD - Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea. Electronic address: sunghwan.kim@kitox.re.kr. FAU - Kim, Jong-Choon AU - Kim JC AD - College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: toxkim@jnu.ac.kr. LA - eng PT - Journal Article DEP - 20170217 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 0 (Allyl Compounds) RN - 0 (Antioxidants) RN - 0 (Bax protein, rat) RN - 0 (Disulfides) RN - 0 (NF-kappa B) RN - 0 (Protective Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (bcl-2-Associated X Protein) RN - 362O9ITL9D (Acetaminophen) RN - 5HI47O6OA7 (diallyl disulfide) RN - 9007-43-6 (Cytochromes c) RN - EC 1.14.13.- (Cytochrome P-450 CYP2E1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Acetaminophen/*adverse effects MH - Allyl Compounds/*pharmacology MH - Animals MH - Antioxidants/metabolism MH - Apoptosis/drug effects MH - Caspase 3/metabolism MH - Cyclooxygenase 2/metabolism MH - Cytochrome P-450 CYP2E1/*metabolism MH - Cytochromes c/metabolism MH - Disulfides/*pharmacology MH - Kidney/*drug effects/metabolism/pathology MH - Kidney Diseases/chemically induced/metabolism MH - Liver/drug effects/metabolism MH - Male MH - NF-kappa B/*metabolism MH - Protective Agents/pharmacology MH - Rats, Sprague-Dawley MH - Tumor Necrosis Factor-alpha/metabolism MH - bcl-2-Associated X Protein/metabolism OTO - NOTNLM OT - Acetaminophen OT - CYP2E1 OT - Diallyl disulfide OT - NF-kappaB OT - Nephrotoxicity OT - Protection EDAT- 2017/02/22 06:00 MHDA- 2017/03/28 06:00 CRDT- 2017/02/22 06:00 PHST- 2016/08/29 00:00 [received] PHST- 2017/01/24 00:00 [revised] PHST- 2017/02/14 00:00 [accepted] PHST- 2017/02/22 06:00 [pubmed] PHST- 2017/03/28 06:00 [medline] PHST- 2017/02/22 06:00 [entrez] AID - S0278-6915(17)30067-4 [pii] AID - 10.1016/j.fct.2017.02.021 [doi] PST - ppublish SO - Food Chem Toxicol. 2017 Apr;102:156-165. doi: 10.1016/j.fct.2017.02.021. Epub 2017 Feb 17.