The compound, diallyl disulfide, enriched in garlic, prevents the progression of doxorubicin-induced nephropathy

San-Chi Lin,Chao-Wen Cheng,Amarzaya Chagnaadorj,Uyanga Bayarsengee,Ting-Kai Leung

doi:10.1590/fst.15418

Abstract

Abstract The main medicinal property of garlic is mostly attributed to its organosulfur compounds, of which the oil-soluble diallyl disulfide (DADS) is the principal component of distilled garlic oil. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important cellular regulator in response to oxidative stress. This study assessed the possible protective effect of DADS on doxorubicin (Dox)-induced nephrotoxicity and its potential regulation of the Nrf2 pathway. Treatment with DADS (200 μM) induced heme oxygenase (HO)-1 and NADPH quinone oxidoreductase 1 (NQO-1) expression in a human proximal tubular cell line. The induction of HO-1 expression was suppressed in Nrf2-silenced cells. In an animal study, pretreatment with DADS relieved Dox-induced albuminuria, increased catalase activity, and reduced the urinary 8-hydroxy-2'-deoxyguanosine level. In addition, DADS ameliorated the severity of glomerulosclerosis and suppressed expressions of fibrotic and inflammatory gene expressions. Our data indicate that DADS, a major component of garlic, showed protective effects of preventing the progression of Dox-induced nephropathy through enhancing Nrf2-mediated antioxidant activity. DADS, a normal constituent of the human diet, merits investigation as a potential antioxidant daily food supplement against free radical-mediated chronic diseases.

Highlights

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular resistance to oxidants; it controls the basal and induced expressions of an array of antioxidant response element (ARE)-dependent genes to regulate physiological and pathophysiological outcomes of oxidant responses
Nrf2 is translocated to nuclei when it is released from its repressive cytosolic protein, Kelch-like ECH-associated protein 1 (Keap1), and activates genes encoded with various antioxidant and phase II enzymes such as heme oxygenase (HO)-1, NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) (Jaramillo & Zhang, 2013; Ma, 2013)
Inasmuch as oxidative stress is a causal pathologic factor for kidney diseases, we first examined whether diallyl disulfide (DADS) induced Nrf2-antioxidant response element-dependent gene expressions

Summary

Introduction

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular resistance to oxidants; it controls the basal and induced expressions of an array of antioxidant response element (ARE)-dependent genes to regulate physiological and pathophysiological outcomes of oxidant responses. Nrf and its downstream genes play very critical roles against oxidative stress and inflammation of the kidneys (Aminzadeh et al, 2013; Pedruzzi et al, 2012). The main medicinal property of garlic is mostly attributed to its organosulfur compounds (OSCs). Allin is very quickly transformed into allicin (diallyl thiosulfinate) by inducing it to release the vacuolar enzyme, alliinase. Allicin is poorly soluble in water but transformed into oil-soluble polysulfides, mostly diallyl disulfide (DADS), and into diallyl sulfide (DAS) and diallyl trisulfide (DATS). Garlic and DADS activated Nrf pathway to induce biogenesis in mitochondria and ameliorates hypertrophy in a isoproterenol induced cardiac hypertrophy rat model (Khatua et al, 2015). DADS protected against CCl4-induced hepatotoxicity, which was related to its ability to induce antioxidant enzymes by activating Nrf (Lee et al, 2015)

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