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

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.

Effectiveness of deferiprone-loaded nanocarrier in experimentally induced rhabdomyolysis: A dose-comparison study.

Herein, the efficacy of free deferiprone (DFP) and DFP-loaded starch/polyethylene glycol/polyacrylic acid (St/PEG/PAAc) nanogel [Nano-DFP] in modulating the biochemical changes induced by glycerol model of rhabdomyolysis (RBD) in male rats was investigated. In this respect, gamma radiation-induced crosslinking was used to produce St/PEG/PAAc nanogel particles, and then, it was used as a nanocarrier for DFP as an attempt to overcome the poor bioavailability and short half-life of DFP. St/PEG/PAAc nanogel was characterized by Fourier transform infrared, dynamic light scattering and Transmission electron microscopy. Free DFP was administered to rats in two doses; 25 and 50 mg following RBD induction, while the loaded nanogel was administered at a dose of 25 mg. The liver and kidney functions were then fully assessed in association with the histological tissue examination of both organs and the femur muscle. Both doses of DFP significantly antagonized the RBD-induced changes in most of the assessed organs functions. The higher dose of DFP, however, showed a statistically more pronounced modulation of RBD effects on each of kidney, liver and skeletal muscles. Nano-DFP; at 25 mg dose, resulted in a statistically significant correction of most of the RBD-related biomarkers with a comparable magnitude to the higher DFP dose rather than the corresponding lower one.