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Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats.
Eur J Pharmacol. 2009 Mar 15; 606(1-3):162-71.EJ

Abstract

The protective role of diallyl sulfide (DAS) in attenuating gentamicin-induced nephrotoxicity has been reported earlier. However, the mechanism of induction of antioxidants by DAS in nephrotoxicity remains elusive. This study is aimed to elucidate the role of a transcription factor, Nuclear factor E2-related factor 2 (Nrf2) in inducing antioxidants and phase II enzymes during gentamicin toxicity in Wistar rats. DAS was administered intraperitoneally at a dosage of 150 mg/kg body weight once daily for 6 days. Gentamicin was administered intraperitoneally at a dosage of 100 mg/kg body weight, once daily for 6 days. Gentamicin-induced rats showed a significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon treatment with DAS. A significant increase in kidney myeloperoxidase (MPO) and lipid peroxidation (LPO) levels was observed in gentamicin-induced rats, which was reduced upon treatment with DAS. Gentamicin-induced rats also showed a significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) in rat kidney, which was increased upon treatment with DAS. Immunohistochemical studies in gentamicin-induced rats demonstrated a marked increase in the immunoreactivity of inducible nitric oxide synthase (iNOS), nuclear transcription factor (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha) that were reduced after treatment with DAS. Further, the involvement of Nrf2 in antioxidant induction was analyzed by Western blot and immunofluorescence. To conclude, DAS enhances antioxidants and suppresses inflammatory cytokines through the activation of Nrf2, thereby protecting the cell against oxidative stress induced by gentamicin.

Authors+Show Affiliations

Department of Biochemistry, University of Madras, Guindy campus, Chennai, Tamil nadu, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19374873

Citation

Kalayarasan, Srinivasan, et al. "Diallyl Sulfide Enhances Antioxidants and Inhibits Inflammation Through the Activation of Nrf2 Against Gentamicin-induced Nephrotoxicity in Wistar Rats." European Journal of Pharmacology, vol. 606, no. 1-3, 2009, pp. 162-71.
Kalayarasan S, Prabhu PN, Sriram N, et al. Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. Eur J Pharmacol. 2009;606(1-3):162-71.
Kalayarasan, S., Prabhu, P. N., Sriram, N., Manikandan, R., Arumugam, M., & Sudhandiran, G. (2009). Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. European Journal of Pharmacology, 606(1-3), 162-71. https://doi.org/10.1016/j.ejphar.2008.12.055
Kalayarasan S, et al. Diallyl Sulfide Enhances Antioxidants and Inhibits Inflammation Through the Activation of Nrf2 Against Gentamicin-induced Nephrotoxicity in Wistar Rats. Eur J Pharmacol. 2009 Mar 15;606(1-3):162-71. PubMed PMID: 19374873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats. AU - Kalayarasan,Srinivasan, AU - Prabhu,Ponnuraj Nagendra, AU - Sriram,Narayanan, AU - Manikandan,Ramar, AU - Arumugam,Munusamy, AU - Sudhandiran,Ganapasam, Y1 - 2009/01/19/ PY - 2008/07/03/received PY - 2008/11/28/revised PY - 2008/12/09/accepted PY - 2009/4/21/entrez PY - 2009/4/21/pubmed PY - 2009/9/2/medline SP - 162 EP - 71 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 606 IS - 1-3 N2 - The protective role of diallyl sulfide (DAS) in attenuating gentamicin-induced nephrotoxicity has been reported earlier. However, the mechanism of induction of antioxidants by DAS in nephrotoxicity remains elusive. This study is aimed to elucidate the role of a transcription factor, Nuclear factor E2-related factor 2 (Nrf2) in inducing antioxidants and phase II enzymes during gentamicin toxicity in Wistar rats. DAS was administered intraperitoneally at a dosage of 150 mg/kg body weight once daily for 6 days. Gentamicin was administered intraperitoneally at a dosage of 100 mg/kg body weight, once daily for 6 days. Gentamicin-induced rats showed a significant increase in the levels of kidney markers and the activities of urinary marker enzymes, which was reversed upon treatment with DAS. A significant increase in kidney myeloperoxidase (MPO) and lipid peroxidation (LPO) levels was observed in gentamicin-induced rats, which was reduced upon treatment with DAS. Gentamicin-induced rats also showed a significant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and quinone reductase (QR) in rat kidney, which was increased upon treatment with DAS. Immunohistochemical studies in gentamicin-induced rats demonstrated a marked increase in the immunoreactivity of inducible nitric oxide synthase (iNOS), nuclear transcription factor (NF-kappaB) and tumor necrosis factor alpha (TNF-alpha) that were reduced after treatment with DAS. Further, the involvement of Nrf2 in antioxidant induction was analyzed by Western blot and immunofluorescence. To conclude, DAS enhances antioxidants and suppresses inflammatory cytokines through the activation of Nrf2, thereby protecting the cell against oxidative stress induced by gentamicin. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19374873/Diallyl_sulfide_enhances_antioxidants_and_inhibits_inflammation_through_the_activation_of_Nrf2_against_gentamicin_induced_nephrotoxicity_in_Wistar_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00005-3 DB - PRIME DP - Unbound Medicine ER -