The Effect of Polyphenols on Kidney Disease: Targeting Mitochondria

Abstract

Mitochondrial function, including oxidative phosphorylation (OXPHOS), mitochondrial biogenesis, and mitochondria dynamics, are essential for the maintenance of renal health. Through modulation of mitochondrial function, the kidneys are able to sustain or recover acute kidney injury (AKI), chronic kidney disease (CKD), nephrotoxicity, nephropathy, and ischemia perfusion. Therapeutic improvement in mitochondrial function in the kidneys is related to the regulation of adenosine triphosphate (ATP) production, free radicals scavenging, decline in apoptosis, and inflammation. Dietary antioxidants, notably polyphenols present in fruits, vegetables, and plants, have attracted attention as effective dietary and pharmacological interventions. Considerable evidence shows that polyphenols protect against mitochondrial damage in different experimental models of kidney disease. Mechanistically, polyphenols regulate the mitochondrial redox status, apoptosis, and multiple intercellular signaling pathways. Therefore, this review attempts to focus on the role of polyphenols in the prevention or treatment of kidney disease and explore the molecular mechanisms associated with their pharmacological activity.

A Synopsis of Current Theories on Drug-Induced Nephrotoxicity

“…Antioxidants, vitamins, and minerals were also demonstrated to prevent gentamicin-induced nephrotoxicity [ 108 ]. In an experimental study, strong antioxidant and nephroprotective activity were revealed for polyphenols (caffeic acid phenethyl ester, curcumin, quercetin, resveratrol, catechin, hesperidin, and ellagic acid [ 109 ]). There was also specific nephroprotective treatment when some nephrotoxic drugs were administered in an experimental study: cilastatin administration, a blocker of megalin receptors and inhibitor of dehydropeptidase-1, reduced nephrotoxicity associated with vancomycin and aminoglycosides.…”

Natural products for kidney disease treatment: Focus on targeting mitochondrial dysfunction

“…GSPE, a natural bioactive compound from plant, exhibits great therapeutic properties through inhibiting oxidative stress and promoting mitochondrial biogenesis ( Ashkar et al, 2022 ). Researches show in streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats, GSPE treatment is able to enhance mitochondrial biogenesis, and ameliorate podocyte injury and apoptosis via AMPK-Sirtuin-1-PGC-1α-TFAM signaling pathway ( Bao et al, 2014 ).…”

“…Hesperetin, a natural bioactive phytochemical from citrus plants, exhibits wide pharmacological therapeutic effects on cancer, cardiovascular diseases and diabetes ( Chen et al, 2019b ; Ashkar et al, 2022 ). Hesperetin also shows renal protective effects by its anti-oxidative properties ( Ashkar et al, 2022 ). Hesperetin can activate Nrf2-ARE signaling pathway via increasing Nrf2 and p-Nrf2 levels in kidney tissue ( Chen et al, 2019b ).…”

“…CAPE, a natural antioxidant, possesses beneficial roles in cadioprotective, neuroprotective and renoprotective effects ( Kamarauskaite et al, 2021 ). Mitochondrial respiratory chain complex I and III are considered to be the main producers of ROS, the impairment of which contribute to mitochondrial ROS formation ( Ashkar et al, 2022 ). CAPE exhibits a strong antioxidant potential on scavenging mitochondrial ROS ( Ashkar et al, 2022 ).…”

“…Mitochondrial respiratory chain complex I and III are considered to be the main producers of ROS, the impairment of which contribute to mitochondrial ROS formation ( Ashkar et al, 2022 ). CAPE exhibits a strong antioxidant potential on scavenging mitochondrial ROS ( Ashkar et al, 2022 ). First, CAPE pretreatment protects complex I activity and inhibits ROS generation in complex II in renal IRI model.…”