Lipoxin A4 attenuated dexamethasone-induced muscle atrophy via activation of PGC-1a/Nrf2/TFAM pathway

Prolonged dexamethasone (DEX) administration causes skeletal muscle atrophy through induction of both oxidative stress and mitochondrial dysfunction. Lipoxin A4 (LXA4) is a recognized antioxidant but its effect against DEX-induced muscle atrophy has not been studied yet. This study aimed to assess the potential ameliorating effect of LXA4 on DEX-induced muscle atrophy and investigate the possible involvement of the mitochondrial dynamics pathway and the redox state in this effect. Forty male rats were divided into four groups; normal control, LXA4-treated, DEX-treated, and LXA4 plus DEX-treated. At the end of the experiment, LXA4 counteracted the effect of DEX on different parameters including muscle weight, muscle strength, serum creatine kinase activity, malondialdehyde and protein carbonyl contents, Na/K-ATPase and citrate synthase activities, mitochondrial transmembrane potential, mitochondrial transcription factor (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). These findings signify the promising therapeutic effect of LXA4 against DEX-induced skeletal muscle atrophy and indicate the possible involvement of LXA4-induced mitochondrial activation in addition to its well-known antioxidant effects. (AU)

Lipoxin A4 attenuated dexamethasone-induced muscle atrophy via activation of PGC-1α/Nrf2/TFAM pathway.

Prolonged dexamethasone (DEX) administration causes skeletal muscle atrophy through induction of both oxidative stress and mitochondrial dysfunction. Lipoxin A4 (LXA4) is a recognized antioxidant but its effect against DEX-induced muscle atrophy has not been studied yet. This study aimed to assess the potential ameliorating effect of LXA4 on DEX-induced muscle atrophy and investigate the possible involvement of the mitochondrial dynamics pathway and the redox state in this effect. Forty male rats were divided into four groups; normal control, LXA4-treated, DEX-treated, and LXA4 plus DEX-treated. At the end of the experiment, LXA4 counteracted the effect of DEX on different parameters including muscle weight, muscle strength, serum creatine kinase activity, malondialdehyde and protein carbonyl contents, Na/K-ATPase and citrate synthase activities, mitochondrial transmembrane potential, mitochondrial transcription factor (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). These findings signify the promising therapeutic effect of LXA4 against DEX-induced skeletal muscle atrophy and indicate the possible involvement of LXA4-induced mitochondrial activation in addition to its well-known antioxidant effects.

Luteolin and 5-flurouracil act synergistically to induce cellular weapons in experimentally induced Solid Ehrlich Carcinoma: Realistic role of P53; a guardian fights in a cellular battle.

BACKGROUND: Solid Ehrlich Carcinoma (SEC) is an undifferentiated tumor used in tumor studies and chemotherapy investigations. AIM: to assess the anti-tumor potential of luteolin when used either alone or combined to 5-fluorouracil (5-FU) against SEC. METHOD: SEC was induced in 40 female mice; they were categorized into 4 equal groups; group I (untreated SEC), group II (5-FU treated SEC), group III (luteolin treated SEC) and group IV (5-FU + luteolin treated SEC). Tumor volume and weight were calculated. P53, p21, caspase 3 and damage regulated autophagy modulator (DRAM) were assessed. Biomarkers of oxidant/antioxidant status in addition to immunohistochemistry for cylin D1 were evaluated. RESULTS: combined administration of luteolin and 5-FU in SEC model increased levels of p53, p21, caspase 3, DRAM and survivability while, tumor volume, weight, thioredoxin reductase one (TR1) activity and cyclin D1 expression showed the reverse with restoration of oxidant/antioxidant indices. CONCLUSION: current results proved the antitumor therapeutic effects of luteolin alone or combined with 5-FU as a novel strategy for cancer therapy.