Silymarin protects PBMC against B(a)P induced toxicity by replenishing redox status and modulating glutathione metabolizing enzymes—An in vitro study

• Published in: Toxicology and applied pharmacology Vol. 247; no. 2; pp. 116 - 128
• Main Authors: Kiruthiga, P.V., Pandian, S. Karutha, Devi, K. Pandima
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.09.2010; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Alpha naphthoflavone; Antioxidant; Antioxidants; Antioxidants - pharmacology; AROMATICS; Benzo(a)pyrene; Benzo(a)pyrene - antagonists & inhibitors; Benzo(a)pyrene - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; CARCINOGENS; Catalase - metabolism; Cell Membrane - drug effects; Chemical agents; DRUGS; Flavonoid; GLUTATHIONE; Glutathione - metabolism; Humans; HYDROCARBONS; IN VITRO; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lipid Peroxidation - drug effects; Medical sciences; ORGANIC COMPOUNDS; Oxidation-Reduction - drug effects; Oxidative Stress - drug effects; PEPTIDES; POLYCYCLIC AROMATIC HYDROCARBONS; POLYPEPTIDES; Protective Agents - pharmacology; PROTEINS; RADIOPROTECTIVE SUBSTANCES; Redox status; RESPONSE MODIFYING FACTORS; Silymarin; Silymarin - pharmacology; Superoxide Dismutase - metabolism; TOXICITY; Toxicology; Tumors; BPQ; FT-IR; LPO; XRE; Benzo(a)pyrene; MDA; Flavonoid; BPDE; TBA; QD; Polycyclic aromatic hydrocarbons; Redox status; GSH; Glutathione; PBS; SSA; GSSG; Alpha naphthoflavone; SOD; ARNT; AhR; TBARS; DNPH-2,4; GR; Antioxidant; PBMC; GPx; PCA; PCC; TCA; Silymarin; B(a)P; ROS; CAT; NEM; PAHs; ANF; PO; Redox state; Hydrocarbon; Enzyme; Toxicity; Polycyclic aromatic compound; In vitro; Prevention; Carcinogen; Polyphenol; Mononuclear cell; Silibinin; Plant origin; Phenols; Drug-metabolizing enzyme
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2010.06.004

PAHs are a ubiquitous class of environmental contaminants that have a large number of hazardous consequences on human health. An important prototype of PAHs, B(a)P, is notable for being the first chemical carcinogen to be discovered and the one classified by EPA as a probable human carcinogen. It undergoes metabolic activation to QD, which generate ROS by redox cycling system in the body and oxidatively damage the macromolecules. Hence, a variety of antioxidants have been tested as possible protectors against B(a)P toxicity. Silymarin is one such compound, which has high human acceptance, used clinically and consumed as dietary supplement around the world for its strong anti-oxidant efficacy. Silymarin was employed as an alternative approach for treating B(a)P induced damage and oxidative stress in PBMC, with an emphasis to provide the molecular basis for the effect of silymarin against B(a)P induced toxicity. PBMC cells exposed to either benzopyrene (1 μM) or silymarin (2.4 mg/ml) or both was monitored for toxicity by assessing LPO, PO, redox status (GSH/GSSG ratio), glutathione metabolizing enzymes GR and GPx and antioxidant enzymes CAT and SOD. This study also investigated the protective effect of silymarin against B(a)P induced biochemical alteration at the molecular level by FT-IR spectroscopy. Our findings were quite striking that silymarin possesses substantial protective effect against B(a)P induced oxidative stress and biochemical changes by restoring redox status, modulating glutathione metabolizing enzymes, hindering the formation of protein oxidation products, inhibiting LPO and further reducing ROS mediated damages by changing the level of antioxidant enzymes. The results suggest that silymarin exhibits multiple protections and it should be considered as a potential protective agent for environmental contaminant induced immunotoxicity.