Creatine Phosphate Sodium

Diabetes accelerates kidney fibrosis through chronic inflammation, oxidative stress, and activation of profibrotic signaling pathways, including TGF-β/Smad and PI3K/Akt. This study investigated the renoprotective effects of phosphocreatine (PCr) in a dual rat model combining STZ-induced diabetes with unilateral ureteral obstruction (UUO)-induced renal fibrosis. PCr was administered intraperitoneally at 20 or 50 mg/kg for eight weeks, starting one-week post-UUO. Renal function, oxidative stress markers, mitochondrial bioenergetics, and inflammatory cytokines (TNF-α, IL-6) were evaluated. Histopathological changes were assessed via Masson's Trichrome, and Sirius Red staining, while protein expression of collagen I, α-SMA, TGF-β, Smad2/3, and PI3K/Akt was analyzed by Western blotting. Diabetic UUO kidneys exhibited impaired renal function, elevated oxidative stress, mitochondrial dysfunction, increased inflammatory cytokines, and upregulation of fibrotic markers along with TGF-β/Smad and PI3K/Akt signaling. PCr treatment dose-dependently ameliorated these alterations, reducing collagen deposition, restoring mitochondrial function, suppressing inflammation, and inhibiting profibrotic signaling. These findings highlight PCr as a potential multi-targeted therapeutic agent for diabetes-associated kidney fibrosis.

Phosphocreatine (PCr), an energy-buffering molecule that supports mitochondrial function, may protect against chemotherapy-induced liver injury. Doxorubicin (DOX)-induced hepatotoxicity, driven by oxidative stress, mitochondrial dysfunction, and apoptosis, remains a major challenge in cancer therapy. This study evaluated the protective effects of PCr against DOX-induced liver injury in mice, focusing on mitochondrial function and apoptosis via the Nrf2/HO-1 and PGC-1α signaling pathways. Male mice were treated with DOX to induce hepatotoxicity, followed by PCr administration. Key apoptosis-related biomarkers including Bax, Cleaved Caspase-3, Bcl-2, TUNEL assay, oxidative stress markers malondialdehyde MDA, superoxide dismutase SOD, catalase CAT, mitochondrial function high-resolution respirometry HRR, and liver enzymes ALT, AST were assessed. PCr treatment improved liver function, reducing ALT and AST levels by ∼68 % and ∼67 %, respectively, compared with DOX. Oxidative stress was attenuated, with MDA decreased by ∼59 %, while antioxidant capacity increased, as SOD and CAT activities rose by ∼150 % and ∼85 %, respectively. Apoptosis was significantly suppressed, with low-dose PCr reducing TUNEL-positive cells by ∼50 % and high-dose PCr by ∼78 % relative to DOX, accompanied by increased Bcl-2 and decreased Bax and Cleaved Caspase-3 expression. Mitochondrial respiratory capacity was also enhanced. Histological analysis confirmed reduced liver damage. These findings suggest that PCr alleviates DOX-induced hepatotoxicity by enhancing mitochondrial function, suppressing apoptosis, and activating the Nrf2/HO-1 and PGC-1α pathways, highlighting its preclinical potential as a protective strategy against chemotherapy-related liver injury.