NAD⁺ ameliorates endotoxin‐induced acute kidney injury in a sirtuin1–dependent manner via GSK‐3β/Nrf2 signalling pathway

Abstract

Sepsis-induced acute kidney injury (AKI) is a frequent complication seen in hospitalized and critically ill patients and is associated with an increased length of hospital stay, development of chronic comorbidities and extremely high mortality. 1,2 Since the pandemic of coronavirus disease 2019 (COVID-19), the kidney is more vulnerable to targeted attacks because the binding site for SARS-CoV-2 (angiotensin-converting enzyme 2) is highly expressed in proximal tubule cells and podocytes. 3,4 Although the growing healthcare burden of the AKI has progressively increased worldwide, there is currently no satisfactory therapy for preventing and treating AKI, [5][6][7]

The sirtuin family in health and disease

“…The NAD + /SIRT1/glycogen synthase kinase-3β/Nrf2 axis is an important mechanism that could protect against AKI and might be a potential therapeutic target in the treatment of AKI. 890 There have been limited studies carried out on the associations between SIRT2, SIRT5-7 and AKI. Acetylation of MAPK phosphatase-1 was significantly increased in SIRT2-knockdown cells and decreased in SIRT2-overexpressed cells after cisplatin stimulation.…”

“…The NAD + /SIRT1/glycogen synthase kinase-3β/Nrf2 axis is an important mechanism that could protect against AKI and might be a potential therapeutic target in the treatment of AKI. 890 …”

4-Octyl itaconate alleviates renal ischemia reperfusion injury by ameliorating endoplasmic reticulum stress via Nrf2 pathway

“…The severity of kidney damage was measured using the tubular injury score (scale: 0–4) according to a previous description. 21…”

Molecular properties and regulation of NAD+ kinase (NADK)

“…Among the NAD + consuming enzymes, sirtuins play a major role in the beneficial effects of NAD + [ 25 ]. For instance, Sirt1 mediates the salutary effect of NAD + in axonal degeneration, and cardiac ischemia reperfusion and acute kidney injuries [ [26] , [27] , [28] ]. However, given that NAD + is the sole precursor of NADP(H) and that the NADP(H)-dependent antioxidant system exerts protective effects, including prevention of aging and disease, NADK-induced NADP(H) production may also account for the salutary actions of NAD + .…”