Eriodictyol attenuates doxorubicin-induced nephropathy by activating the AMPK/Nrf2 signalling pathway

Doxorubicin (DOX), an anthracycline chemotherapy, plays a prominent role in the treatment of various cancers. Unfortunately, its nephrotoxic effects limit its dosing and expose cancer survivors to increased morbidity and mortality. This study examined the nephroprotective effects of eriodictyol, a natural polyphenolic flavanone, in DOX-treated rats and the molecular pathways involved. Forty adult rats were divided into five groups (8/group): Control; eriodictyol (20 mg/kg/day); DOX (2.5 mg/kg, twice/week); DOX + Eriodictyol; and DOX + Eriodictyol + Compound C (CC), an AMPK inhibitor (0.2 mg/kg/day). Experiments continued for 21 days. Eriodictyol administration in DOX-treated rats reduced their fasting glucose levels and increased food intake, final body weight, and kidney weight, improved kidney function, prevented glomerular and tubular damage, and reduced collagen deposition and renal TGF-β1 mRNA levels. Furthermore, eriodictyol reduced their renal levels of Bax, caspase-3, and cytochrome-c; and enhanced the levels of Bcl2. Noticeably, in the kidneys of both controls and DOX-treated rats, eriodictyol increased levels of phosphorylated-AMPK(Thr172) but not AMPK mRNA nor protein levels. Also, in the same two groups, eriodictyol increased mRNA and nuclear Nrf2 levels, and levels of glutathione, superoxide dismutase, catalase, and hemeoxygenase-1, but reduced the levels of malonaldehyde, TNF-α, and mRNA, total, and nuclear levels of NF-κB. All the detected nephroprotective effects and improvements in the levels of markers of oxidation and inflammation were prevented by coadministration of CC. In conclusion, the coadministration of eriodictyol and DOX alleviates DOX-induced renal damage. In renal tissues, eriodictyol is an AMPK activator and its nephroprotective antioxidant and anti-inflammatory effects are AMPK-dependent

Do obese patients with primary knee osteoarthritis benefit from a single bout of moderate intensity aerobic exercise?

Abstract Background Obesity and osteoarthritis are often concomitant. Both are accompanied by oxidative stress and stimulated inflammatory response. Exercise is considered a substantial treatment in rehabilitation of both conditions. Yet most of literature reported the benefits of regular exercising, while there is paucity about the effects of single low to moderate exercise session. This study aimed to investigate the possible potential effects of a single bout of moderate exercise in obese middle-aged individuals with knee osteoarthritis (KOA). Results Score of pain and Western Ontario and Mc-Master University (WOMAC) had been improved 24 h after exercise. Glutathione reductase (GR) activity increased post-exercise but decreased the next 24 h though remained higher than baseline. Blood glucose level was reduced post-exercise whereas blood lipids still uninfluenced by exercise. Markers of inflammation remained unchanged after exercise session. Conclusion A single bout moderate-intensity aerobic exercise is effective in improving pain and antioxidant activity among middle-aged obese patients with primary knee OA. Single bout of mild to moderate exercise may help in treatment of obese patients with KOA. Trial registration Clinical Trials.gov Identifier: NCT0392733