title: Silymarin regulates the cytochrome P450 3A2 and glutathione peroxides in the liver of streptozotocin-induced diabetic rats.
abstract: This study aimed to investigate the protective and regulatory effects of silymarin (SMN) and melatonin (MEL) on streptozotocin (STZ)-induced diabetic changes in cytochrome P450 3A2 (CYP 3A2) and glutathione peroxidase (GPX) expression and antioxidant status in the liver. Male Wistar rats were divided into five groups, including: control (C), untreated diabetic animals (D), SMN-treated diabetics (S, 50 mg/kg, orally), MEL-treated diabetics (M, 10 mg/kg, i.p.), and SMN plus MEL-treated diabetics (S+M). Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). The blood glucose level, daily urinary volume and body weight changes were measured. After the 28 days treatment period, antioxidant status was analyzed by means of the determination of malondialdehyde (MDA) content, nitric oxide (NO) and total thiol molecules (TTM) levels in the liver. The glycogen depletion in the liver was examined by histochemical staining. The CYP 3A2 and GPX expression at mRNA level was determined using RT-PCT technique. SMN and MEL both individually or in combination prevented from diabetes-induced weight loss and lowered daily urinary volume significantly (p<0.05). None of the test compounds could lower the blood glucose level significantly (p>0.05). Both SMN and MEL could convert the diabetes induced elevated levels of MDA and NO and the diabetes-reduced TTM content to the control level. Moreover, the diabetes-up regulated CYP 3A2 and down regulated GPX, returned to normal values after SMN treatment. Histochemical and histopathological examinations revealed that the diabetes-induced glycogen-depletion and single cell necrosis markedly improved with the SMN and SMN plus MEL treatment. Our data suggest that the STZ-induced diabetes in addition of disturbing the antioxidant status, alters the expression levels of CYP 3A2 and GPX. Moreover, the SMN and SMN plus MEL treatment was able to normalize both the antioxidant status and the expression of CYP 3A2 and GPX in the liver of diabetic rats.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. hassanmalekinejad@yahoo.com
authors.forename: H
authors.initials: H
authors.lastname: Malekinejad
authors.forename: A
authors.initials: A
authors.lastname: Rezabakhsh
authors.forename: F
authors.initials: F
authors.lastname: Rahmani
authors.forename: R
authors.initials: R
authors.lastname: Hobbenaghi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D020944:Silybum marianum / Q000737:chemistry; D009336:Necrosis / Q000188:drug therapy; D009569:Nitric Oxide / Q000097:blood; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000097:blood; D014554:Urination / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D010936:Plant Extracts; D012333:RNA, Messenger; D012838:Silymarin; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D008315:Malondialdehyde; D006003:Glycogen; D005979:Glutathione Peroxidase; D051544:Cytochrome P-450 CYP3A; D008550:Melatonin