The Beneficial Effects of Allicin in Chronic Kidney Disease Are Comparable to Losartan

Abstract

Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex. The levels of angiotensin receptors and endothelial nitric oxide synthase (eNOS) were decreased in the renal cortex from the CKD group. Otherwise, lipid and protein oxidation were higher in the CKD group than in the control group. A disturbance was observed in the expression levels of the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 system (Nrf2/keap1) and the antioxidant enzymes catalase, superoxide dismutase, and heme oxygenase-1. Allicin or losartan treatments relieved renal dysfunction, hypertension, and oxidative stress. In addition, both treatments showed the same efficacy on the expression of angiotensin receptors, the nephrin, Nrf2/keap1 pathway, and eNOS. Further in silico analyses suggest that allicin and losartan could have a common mechanism involving interaction with AT1 receptors. Allicin showed antihypertensive, antioxidant, and nephroprotective effects. The beneficial effects showed by allicin are similar, or even better, than those of losartan. In fact, the effect of allicin on blood pressure and renal function is comparable to reductions seen with losartan, a prescription drug commonly used as a first-line therapy.

Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy

“…The oxidative stress in diabetes was attenuated at protein and lipid levels by the allicin treatment. Previously, using an experimental model of chronic kidney disease (CKD) by renal ablation we observed an antioxidant effect of allicin by a mechanism dependent on the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 (Nrf2/Keap1) pathway [ 9 ]. Other studies reported antioxidant properties of allicin by scavenging free radicals and hydroxyl radicals (OH•) [ 22 ] and indirectly up-regulating the phase II detoxifying enzymes [ 23 ].…”

“…Allicin was produced by oxidation of diallyl disulfide as previously reported [ 9 ]. For stabilization and storage, allicin was resuspended in water at 2.5% ( w / v ) and kept at −70 °C until used.…”

“…Diallyl thiosulfinate (allicin) is a major component formed when garlic ( Allium sativum ) is crushed or ground [ 8 ]. Allicin is considered as a panacea as it has a broad spectrum of physiological activities such as antihypertensives [ 9 , 10 ], antioxidants [ 9 ], antidiabetics [ 11 ], cardioprotectives [ 10 ], nephroprotectives [ 11 ], and immunomodulators [ 12 , 13 ]. As far as nephroprotective mechanisms of allicin in experimental DN are concerned, recent studies have shown that this garlic derivative partially reverses the increased expression of transforming growth factor β (TGF-β) and the activation (i.e., phosphorylation) of its downstream target extracellular signal-regulated kinase ½ (ERK1/2) that drive renal epithelial-mesenchymal transition and fibrosis [ 11 ].…”

Inflammation and Oxidative Stress in Chronic Kidney Disease—Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites

“…In fact, allicin has been shown to improve renal function by modulation of AT1, Nrf2/Keap1 and eNOS pathways. The beneficial effects demonstrated by allicin are similar or even better, than those of losartan, a drug commonly used as a first-line therapy [168]. By increasing the nuclear translocation of the Nrf2 factor, allicin also increases the gene transcription of Nrf2-related enzymes, such as CAT, SOD and GPx, which play a key role in the cellular mechanisms defending against oxidative damage.…”

Phenethyl Isothiocyanate, a Dual Activator of Transcription Factors NRF2 and HSF1

“…Through activation of NRF2, PEITC restored insulin‐stimulated glucose uptake, translocation of glucose transporter 4, and insulin signaling that were impaired by treatment of 3T3‐L1 adipocytes with hydrogen peroxide,27 demonstrating the cytoprotective role of PEITC under conditions of dysregulated glucose metabolism. Dietary administration of PEITC reduced mucosal and submucosal inflammation, glandular atypia, and tumor development in a mouse model of colitis‐associated colorectal carcinogenesis 28. PEITC was also suggested as one potential dietary agent for the prevention and treatment of malignant mesothelioma 29.…”