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Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway.
Int Immunopharmacol 2017; 50:107-120II

Abstract

BACKGROUND

Arsenic (As) contamination is an extremely dangerous global environmental problem as it can enter into the food chain and become bio-accumulated, endangering human health. Chronic As intoxication leads to undesirable toxic effects in various organ systems of the body, especially the kidney. Diallyl trisulfide (DATS) is an organosulfur compound which has been widely known for its uses as antibacterial, antitumorogenic, antioxidant agent and has been also reported to have anti-apoptotic and anti-inflammatory properties.

PURPOSE

In the present work, we intend to investigate the protective role of DATS, a garlic organosulfur compound in preventing the As-induced oxidative stress mediated renal injury in rats. Study design The activity of DATS to antagonize As-induced renal oxidative toxicity was analyzed using rats as an in vivo model.

METHODS

We investigated the nephroprotective effect of DATS on As treated rats by performing various serological, biochemical, molecular and histological studies. The activation of Nrf2 was investigated using western blot.

RESULTS

The data showed that As exposure significantly increased the serum and urine nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. As intoxication also decreased the antioxidant status of the renal tissue along with the disturbances in the membrane bound ATPases. As nephrotoxicity was further confirmed with the altered morphological and ultrastructural changes in the renal tissue. Conversely, the DATS pre-administration effectively recuperate the altered renal variables by As, which has been further supported by the histological and ultrastructural observations. This counteraction was achieved partially via the activation of Nrf2-ARE pathway through the activation of Akt.

CONCLUSION

These findings explicate the prospective use of DATS as a promising organosulfur compound against As-induced renal oxidative dysfunction in rats.

Authors+Show Affiliations

Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India. Electronic address: miltonprabu@hotmail.com.Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.Division of Bioinformatics, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28648972

Citation

Miltonprabu, S, et al. "Diallyl Trisulfide, a Garlic Polysulfide Protects Against As-induced Renal Oxidative Nephrotoxicity, Apoptosis and Inflammation in Rats By Activating the Nrf2/ARE Signaling Pathway." International Immunopharmacology, vol. 50, 2017, pp. 107-120.
Miltonprabu S, Sumedha NC, Senthilraja P. Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway. Int Immunopharmacol. 2017;50:107-120.
Miltonprabu, S., Sumedha, N. C., & Senthilraja, P. (2017). Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway. International Immunopharmacology, 50, pp. 107-120. doi:10.1016/j.intimp.2017.06.011.
Miltonprabu S, Sumedha NC, Senthilraja P. Diallyl Trisulfide, a Garlic Polysulfide Protects Against As-induced Renal Oxidative Nephrotoxicity, Apoptosis and Inflammation in Rats By Activating the Nrf2/ARE Signaling Pathway. Int Immunopharmacol. 2017;50:107-120. PubMed PMID: 28648972.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway. AU - Miltonprabu,S, AU - Sumedha,N C, AU - Senthilraja,P, Y1 - 2017/06/23/ PY - 2016/12/08/received PY - 2017/05/28/revised PY - 2017/06/13/accepted PY - 2017/6/27/pubmed PY - 2018/5/10/medline PY - 2017/6/27/entrez KW - Antioxidant KW - As KW - Diallyl trisulfide KW - Nrf2/Keap1 KW - Rats KW - Renal injury SP - 107 EP - 120 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 50 N2 - BACKGROUND: Arsenic (As) contamination is an extremely dangerous global environmental problem as it can enter into the food chain and become bio-accumulated, endangering human health. Chronic As intoxication leads to undesirable toxic effects in various organ systems of the body, especially the kidney. Diallyl trisulfide (DATS) is an organosulfur compound which has been widely known for its uses as antibacterial, antitumorogenic, antioxidant agent and has been also reported to have anti-apoptotic and anti-inflammatory properties. PURPOSE: In the present work, we intend to investigate the protective role of DATS, a garlic organosulfur compound in preventing the As-induced oxidative stress mediated renal injury in rats. Study design The activity of DATS to antagonize As-induced renal oxidative toxicity was analyzed using rats as an in vivo model. METHODS: We investigated the nephroprotective effect of DATS on As treated rats by performing various serological, biochemical, molecular and histological studies. The activation of Nrf2 was investigated using western blot. RESULTS: The data showed that As exposure significantly increased the serum and urine nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. As intoxication also decreased the antioxidant status of the renal tissue along with the disturbances in the membrane bound ATPases. As nephrotoxicity was further confirmed with the altered morphological and ultrastructural changes in the renal tissue. Conversely, the DATS pre-administration effectively recuperate the altered renal variables by As, which has been further supported by the histological and ultrastructural observations. This counteraction was achieved partially via the activation of Nrf2-ARE pathway through the activation of Akt. CONCLUSION: These findings explicate the prospective use of DATS as a promising organosulfur compound against As-induced renal oxidative dysfunction in rats. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/28648972/Diallyl_trisulfide_a_garlic_polysulfide_protects_against_As_induced_renal_oxidative_nephrotoxicity_apoptosis_and_inflammation_in_rats_by_activating_the_Nrf2/ARE_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(17)30233-3 DB - PRIME DP - Unbound Medicine ER -