N-acetylcysteine modulates cyclophosphamide-induced immunosuppression, liver injury, and oxidative stress in miniature pigs
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Cyclophosphamide, a cytotoxic anticancer agent, induces immunosuppression and has several adverse effects. N-acetylcysteine alleviates oxidative stress, liver injury, and intestinal tissue damage. The present study examined whether N-acetylcysteine modulates the adverse effects of cyclophosphamide in pigs. Miniature pigs (n = 15) were used as an experimental model to evaluate the effects of N-acetylcysteine treatment on immune reactions, liver injury, and oxidative stress after cyclophosphamide challenge. Corn-soybean meal based dietary treatments were as follows: control diet with either saline injection, cyclophosphamide injection, or 0.5% N-acetylcysteine and cyclophosphamide injection. N-acetylcysteine increased the number of immune cells and decreased TNF-α production after cyclophosphamide injection and decreased TNF-α, IFN-γ, NF-κB, and IL-8 expression and increased IL- 10 expression in peripheral blood mononuclear cells. Serum levels of alanine transaminase and aspartate aminotransferase decreased, superoxide dismutase activity increased, and malondialdehyde activity decreased following N-acetylcysteine treatment after cyclophosphamide injection. N-acetylcysteine decreases immunosuppression, liver injury, and oxidative stress in cyclophosphamide-challenged miniature pigs. The present study suggests that N-acetylcysteine has therapeutic application in livestock for modulating immune reactions, liver injury, and oxidative stress.
Abstract
Cyclophosphamide, a cytotoxic anticancer agent, induces immunosuppression and has several adverse effects. N-acetylcysteine alleviates oxidative stress, liver injury, and intestinal tissue damage. The present study examined whether N-acetylcysteine modulates the adverse effects of cyclophosphamide in pigs. Miniature pigs (n = 15) were used as an experimental model to evaluate the effects of N-acetylcysteine treatment on immune reactions, liver injury, and oxidative stress after cyclophosphamide challenge. Corn-soybean meal based dietary treatments were as follows: control diet with either saline injection, cyclophosphamide injection, or 0.5% N-acetylcysteine and cyclophosphamide injection. N-acetylcysteine increased the number of immune cells and decreased TNF-α production after cyclophosphamide injection and decreased TNF-α, IFN-γ, NF-κB, and IL-8 expression and increased IL- 10 expression in peripheral blood mononuclear cells. Serum levels of alanine transaminase and aspartate aminotransferase decreased, superoxide dismutase activity increased, and malondialdehyde activity decreased following N-acetylcysteine treatment after cyclophosphamide injection. N-acetylcysteine decreases immunosuppression, liver injury, and oxidative stress in cyclophosphamide-challenged miniature pigs. The present study suggests that N-acetylcysteine has therapeutic application in livestock for modulating immune reactions, liver injury, and oxidative stress.
참고문헌 (30)
- El-Abasy M, "Preventive and therapeutic effects of sugar cane extract on cyclophosphamide-induced immunosuppression in chickens", Int Immunopharmacol, 4, pp.983~990 (2004)
- Tayade C, "L-arginine stimulates immune response in chickens immunized with intermediate plus strain of infectious bursal disease vaccine", Vaccine, 24, pp.552~560 (2006)
- Huttunen KM, "Prodrugs-from serendipity to rational design", Pharmacol Rev, 63, pp.750~771 (2011)
- Salem ML, "Recovery from cyclophosphamide-induced lymphopenia results in expansion of immature dendritic cells which can mediate enhanced prime-boost vaccination antitumor responses in vivo when stimulated with the TLR3 agonist poly(I : C)", J Immunol, 182, pp.2030~2040 (2009)
- Montgomery M, "Mobilization and collection of autologous hematopoietic progenitor", stem cells, 2007, pp.5, 127~136
- Ochoa R, "Pneumonitis and pulmonary fibrosis in a patient receiving adjuvant docetaxel and cyclophosphamide for stage 3 breast cancer : a case report and literature review", J Med Case Rep, 6, pp.413~ (2012)
- Shepherd JD, "Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation", J Clin Oncol, 9, pp.2016~2020 (1991)
- Paul R, "Avocado fruit(Persea americana Mill)exhibits chemo-protective potentiality against cyclophosphamide induced genotoxicity in human lymphocyte culture", J Exp Ther Oncol, 9, pp.221~230 (2011)
- Ozkan HA, "Assessment and comparison of acute cardiac toxicity during high-dose cyclophosphamide and high-dose etoposide stem cell mobilization regimens with N-terminal pro-B-type natriuretic peptide", Transfus Apher Sci, 50, pp.46~52 (2014)
- Salem ML, "Cyclophosphamide induces dynamic alterations in the host microenvironments resulting in a Flt3ligand-dependent expansion of dendritic cells", J Immunol, 184, pp.1737~1747 (2010)
- Wu G, "Glutathione metabolism and its implications for health", J Nutr, 134, pp.489~492 (2004)
- Wu G, "Amino acids : metabolism, functions, and nutrition", Amino acids, 37, pp.1~17 (2009)
- Hou Y, "N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling", Amino Acids, 45, pp.513~522 (2013)
- Yi D, "Dietary N-acetylcysteine supplementation alleviates liver injury in lipopolysaccharide-challenged piglets", Br J Nutr, 111, pp.46~54 (2014)
- Unal F, "The role of N-acetylcysteine in preventing cyclophosphamide-induced gonadotoxicity : an experimental study in rats", J Obstet Gynaecol, 36, pp.372~375 (2016)
- Gurbuz N, "Effects of vitamin C and N-acetylcysteine against cyclophosphamide-induced genotoxicity in exfoliated bladder cells of mice in vivo", J BUON, 14, pp.647~652 (2009)
- Svendsen O, "The minipig in toxicology", Exp Toxicol Pathol, 57, pp.335~339 (2006)
- National Research Council, "Nutrient requirements of swine" (2012), National Academy Press
- Lee SI, "Lactobacillus acidophilus modulates inflammatory activity by regulating the TLR4 and NF-κB expression in porcine peripheral blood mononuclear cells after lipopolysaccharide challenge", Br J Nutr, 115, pp.567~575 (2016)
- Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T))Method", Methods, 25, pp.402~408 (2001)
- Han J, "Dietary L-arginine supplementation alleviates immunosuppression induced by cyclophosphamide in weaned pigs", Amino Acids, 37, pp.643~651 (2009)
- Jordan HL, "Nontraditional applications in clinical pathology", Toxicol Pathol, 42, pp.1058~1068 (2014)
- Ganderup NC, "The minipig as nonrodent species in toxicology-where are we now?", Int J Toxicol, 31, pp.507~528 (2012)
- de Mello VDF, "Gene expression of peripheral blood mononuclear cells as a tool in dietary intervention studies: what do we know so far?", Mol Nutr Food Res, 56, pp.1160~1172 (2012)
- Carpenter S, "How important are toll-like receptors for antimicrobial responses?", Cell Microbiol, 9, pp.1891~1901 (2007)
- Baeuerle PA, "Function and activation of NF-kappa B in the immune system", Ann Rev Immunol, 12, pp.141~179 (1994)
- Yu BP, "Cellular defenses against damage from reactive oxygen species", Physiol Rev, 74, pp.139~162 (1994)
- Xu CC, "Regulation of N-acetyl cysteine on gut redox status and major microbiota in weaned piglets", J Anim Sci, 92, pp.1504~1511 (2014)
- Germoush MO, "Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating antioxidant status and inflammatory cytokines", J Cancer Res Clin Oncol, 140, pp.1103~1109 (2014)
- Kumar G, "Antihepatotoxic effect of beta-carotene on paracetamol induced hepatic damage in rats", Indian J Exp Biol, 43, pp.351~355 (2005)