ABSTRACT
Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1ß], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.
Subject(s)
Antioxidants , Chemical and Drug Induced Liver Injury , Humans , Antioxidants/pharmacology , NF-E2-Related Factor 2/metabolism , Heme Oxygenase-1/metabolism , Inflammation/drug therapy , Oxidative Stress , Cyclophosphamide/adverse effects , NF-kappa B/metabolism , Apoptosis , Glutathione/adverse effects , Chemical and Drug Induced Liver Injury/drug therapyABSTRACT
The influence of charcoal as feed additives on carcass and meat characteristics was studied in 144 four weeks old Muller ducks. The experimental ducklings were assigned to six groups of 24 birds (Eight per replicates each). The dietary treatments contained 0, 0.5, 1.0, 1.5, 2.0, and 2.5% charcoal for G1 (C), G2 (L1), G3 (L2), G4 (L3), G5 (L4) and G6 (L5), respectively. All experimental birds were raised under similar environmental and managerial conditions. Results indicated that charcoal did not affect most carcass traits significantly except for dressing percentage was higher (P < 0.05) in 1.5 and 2 % charcoal included ducks diets compared to control ducks. Charcoal supplementation significantly affected duck meat tenderness, juiciness and water holding capacity. Moreover, charcoal altered (P < 0.05) meat components such as crude protein, calcium components, desirable fatty acids, nutritional value and some bacterial counts. Thiobarbituric acid reactive substances reduced in birds fed charcoal at 1.5, 2, and 2.5%, with significant variation among treatments. No significant differences in the number of Escherichia coli and Staphylococcus aureus were detected among the ducks fed with charcoal and the control group. It could be concluded that charcoal could be included in ducks' diets at 1.5 and 2% with beneficial effects on carcass parameters.