Effects of Allicin on Pathophysiological Mechanisms during the Progression of Nephropathy Associated to Diabetes
Abraham Said Arellano-Buendía,
Luis Gerardo Castañeda-Lara,
María L. Loredo-Mendoza,
Fernando E. García-Arroyo,
Pedro Rojas-Morales,
Raúl Argüello-García,
Juan G. Juárez-Rojas,
Edilia Tapia,
José Pedraza-Chaverri,
Laura Gabriela Sánchez-Lozada,
Horacio Osorio-Alonso
Affiliations
Abraham Said Arellano-Buendía
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
Luis Gerardo Castañeda-Lara
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
María L. Loredo-Mendoza
Histopathology Laboratory, Research Subdivision, School of Medicine, Universidad Panamericana, Donatello 43, Mexico City 03910, Mexico
Fernando E. García-Arroyo
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
Pedro Rojas-Morales
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
Raúl Argüello-García
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico
Juan G. Juárez-Rojas
Department of Endocrinology, Instituto Nacional de Cardiología “Ignacio Chávez” México City 14080, Mexico
Edilia Tapia
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
José Pedraza-Chaverri
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico
Laura Gabriela Sánchez-Lozada
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
Horacio Osorio-Alonso
Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
This study aimed to assess the impact of allicin on the course of diabetic nephropathy. Study groups included control, diabetes, and diabetes-treated rats. Allicin treatment (16 mg/kg day/p.o.) started after 1 month of diabetes onset and was administered for 30 days. In the diabetes group, the systolic blood pressure (SBP) increased, also, the oxidative stress and hypoxia in the kidney cortex were evidenced by alterations in the total antioxidant capacity as well as the expression of nuclear factor (erythroid-derived 2)-like 2/Kelch ECH associating protein 1 (Nrf2/Keap1), hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), erythropoietin (Epo) and its receptor (Epo-R). Moreover, diabetes increased nephrin, and kidney injury molecule-1 (KIM-1) expression that correlated with mesangial matrix, the fibrosis index and with the expression of connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA). The insulin levels and glucose transporter protein type-4 (GLUT4) expression were decreased; otherwise, insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) expression was increased. Allicin increased Nrf2 expression and decreased SBP, Keap1, HIF-1α, and VEGF expression. Concurrently, nephrin, KIM-1, the mesangial matrix, fibrosis index, and the fibrotic proteins were decreased. Additionally, allicin decreased hyperglycemia, improved insulin levels, and prevented changes in (GLUT4) and IRSs expression induced by diabetes. In conclusion, our results demonstrate that allicin has the potential to help in the treatment of diabetic nephropathy. The cellular mechanisms underlying its effects mainly rely on the regulation of antioxidant, antifibrotic, and antidiabetic mechanisms, which can contribute towards delay in the progression of renal disease.
