Piceatannol promotes hepatic and renal AMPK/SIRT1/PGC-1α mitochondrial pathway in rats exposed to reserpine or gamma-radiation

Abstract

Human exposure to radio-therapeutic doses of gamma rays can produce late effects, which negatively affect cancer patients’ quality of life, work prospects, and general health. This study was performed to explore the role of Piceatannol (PIC) in the process of “mitochondrial biogenesis” signaling pathway as possible management of disturbances induced in stressed animal model(s) either by gamma-irradiation (IR) or administration of reserpine (RES); as a mitochondrial complex-I inhibitor. PIC (10 mg/kg BW/day; orally) were given to rats for 7 days, after exposure to an acute dose of γ-radiation (6 Gy), or after a single reserpine injection (1 g/kg BW; sc). Compared to reserpine or γ-radiation, PIC has attenuated hepatic and renal mitochondrial oxidative stress denoted by the significant reduction in the content of lipid peroxides and NO with significant induction of SOD, CAT, GSH-PX, and GR activities. PIC has also significantly alleviated the increase of the inflammatory markers, TNF-α and IL-6 and apoptotic markers, cytochrome c, and caspase-3. The decrease of oxidative stress, inflammation, and apoptotic responses were linked to a significant amelioration in mitochondrial biogenesis demonstrated by the increased expression and proteins’ tissue contents of SIRT1/p38-AMPK, PGC-1α signaling pathway. The results are substantiated by the significant amelioration in mitochondrial function verified by the higher levels of ATP content, and complex I activity, besides the improvement of hepatic and renal functions. Additionally, histopathological examinations of hepatic and renal tissues showed that PIC has modulated tissue architecture after reserpine or gamma-radiation-induced tissue damage. Piceatannol improves mitochondrial functions by regulating the oxidant/antioxidant disequilibrium, the inflammatory and apoptotic responses, suggesting its possible use as adjuvant therapy in radio-therapeutic protocols to attenuate hepatic and renal injuries.

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“…Piceatannol exhibits versatile pharmacologic therapeutic potencies in cancer, cardiovascular diseases and atherosclerosis, as well as in kidney diseases ( Tovar-Palacio et al, 2022 ). Piceatannol can ameliorate necrosis and apoptosis in renal TECs through activating Sirtuin-1-PGC-1α pathway ( Mahmoud Moustafa et al, 2021 ).…”

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“…Piceatannol (PC), a polyphenol found in grapes and other plants such as passion fruit or sugar cane, is a RV analog [ 144 ] that is also an active SIRT1 [ 168 ]. However, PC structure confers a higher capability to scavenge ROS by modulating other pathways as well [ 143 ].…”

“…However, PC structure confers a higher capability to scavenge ROS by modulating other pathways as well [ 143 ]. The mechanisms of PC mitigation of ROS involve stimulation of antioxidant enzymes such as SOD and CAT activities [ 144 , 145 ]. Moreover, PC improves mitochondrial functions by increasing complex I activity and ATP content [ 144 ].…”

“…The mechanisms of PC mitigation of ROS involve stimulation of antioxidant enzymes such as SOD and CAT activities [ 144 , 145 ]. Moreover, PC improves mitochondrial functions by increasing complex I activity and ATP content [ 144 ]. PC has been demonstrated to induce mitochondrial biogenesis through the increase of expression and protein levels of SIRT1 and PGC1α under gamma-irradiation [ 144 ].…”

“…Moreover, PC improves mitochondrial functions by increasing complex I activity and ATP content [ 144 ]. PC has been demonstrated to induce mitochondrial biogenesis through the increase of expression and protein levels of SIRT1 and PGC1α under gamma-irradiation [ 144 ]. On the other hand, apoptosis is reduced by PC increase of anti and pro-apoptotic proteins such as Bcl-2 and BAX, respectively [ 145 ].…”