title: Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-κB.
abstract: 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.
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: 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.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Shin
authors.affiliation: Department of Food and Nutrition, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Jeong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Sung-Hyeuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Na-Rae
authors.initials: NR
authors.lastname: Shin
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup 53212, Republic of Korea. Electronic address: sunghwan.kim@kitox.re.kr.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; C494828:Bax protein, rat; D004220:Disulfides; D016328:NF-kappa B; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D000082:Acetaminophen; C028009:diallyl disulfide; D045304:Cytochromes c; D019392:Cytochrome P-450 CYP2E1; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D053148:Caspase 3
keywords: Acetaminophen; CYP2E1; Diallyl disulfide; NF-κB; Nephrotoxicity; Protection