GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney

Abstract

Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

“…Astonishingly, this is the only time that microRNA-205 has been studied in renal tubular cells under oxidative stress, and the efficacy of microRNA-205 in reversing kidney damage remains to be determined. Liu et al uncovered Pb-induced redox signaling in rat kidney was attenuated by grape seed procyanidin extract treatment through Nrf2 signaling pathway activation and microRNA-153 suppression for the first time [105], providing new insight into the prevention and regression of Pb-induced nephrotoxicity. Unfortunately, although the anti-oxidation of grape seed procyanidin in lessening kidney injury has been further validated in a series of studies, the potential of microRNA-153 inhibition was rarely covered, which severely impeded their clinical use [106].…”

“…Furthermore, the burden of myriad diseases attributable to heavy metal pollution is becoming a global health problem [161]. Studies aimed at investigating the relationship of natural products as well as oxidative stress and metal-induced kidney diseases [105]. Unfortunately, although the extracts of Salvia miltiorrhiza and grape seed procyanidin have made survival possible for patients with chronic renal failure and nephrotoxicity, there is a paucity of sufficient knowledge on active ingredients and their potential adverse effects, which severely restricts the clinical use.…”

CaMKII is involved in subcellular Ca2+ redistribution-induced endoplasmic reticulum stress leading to apoptosis in primary cultures of rat proximal tubular cells exposed to lead

“…The persistence of Pb in humans and its associated health risks are a matter of serious concern and a global issue. As a multi-organ toxicant, Pb exerts potent toxic effects on different tissues [ 2 – 7 ]. Kidney is one of the most sensitive targets organs for Pb toxicity, and the proximal tubule is the major site of Pb-induced renal injury [ 2 , 4 , 7 ].…”

Grape Seed Proanthocyanidin Extract Adjusts NeuN/GFAP in a Murine Model of Neonatal Hypoxic-ischemic Brain Injury

“…Grape seed proanthocyanidin extract (GSPE) is a polyphenolic compound [6][7] that is a common natural antioxidant [8]. GSPE treatment has shown good therapeutic effects in models of esophageal squamous cell carcinoma [9], hypertension [10], diabetes [11], and other diseases.…”