title: Silymarin preconditioning protected insulin resistant rats from liver ischemia-reperfusion injury: role of endogenous H2S.
abstract: Hydrogen sulfide (H2S) can protect against hepatic ischemia-reperfusion injury (HIR). However, it is unknown whether it can protect against HIR in insulin resistance. This study investigated the protective effects of silymarin against HIR in a rat model of insulin resistance and the possible involvement of endogenous H2S.
  
  
  
  Insulin resistance was first established using 10% fructose in drinking water for 10 weeks. HIR was conducted in fructose-fed rats treated with saline or silymarin (100 mg/kg), 15 min before HIR (30 min ischemia, followed by 1 h reperfusion). Insulin resistance and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), total nitrites (NO2(-)), and H2S were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), hydroxyproline, H2S synthesizing activity, and mRNA expression of cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) were determined. Additionally, histopathological examination involved H&E, Sirius red, and caspase-3 immunostaining.
  
  
  
  Fructose-induced insulin resistance increased serum ALT, TNF-α, H2S and H2S synthesizing activity, and hepatic MDA, hydroxyproline, and CSE mRNA and decreased NO2(-) and GSH. These changes exacerbated the HIR injury in which endogenous H2S production was auxiliary increased. Silymarin preconditioning decreased ALT, AST, MDA, NO2(-), TNF-α, and TNF-α/IL-10 ratio, increased GSH, IL-10, improved hepatic architecture, and lowered caspase-3 immunostaining. Serum H2S, its hepatic synthesizing activity, and CSE and CBS mRNA expressions were all suppressed by silymarin pretreatment.
  
  
  
  The increases in endogenous H2S exacerbate HIR injury, whereas silymarin preconditioning protected against HIR in insulin resistant rats via powerful antioxidant, anti-inflammatory, and antiapoptotic effects along with suppressing H2S production.
authors: Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors: Nahla N
authors: NN
authors: Younis
authors: Department of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors: Mohamed A
authors: MA
authors: Shaheen
authors: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: mona_pharmacology@yahoo.com.
authors: Mona F
authors: MF
authors: Mahmoud
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D005632:Fructose; D006862:Hydrogen Sulfide / Q000097:blood*; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress; D008517:Phytotherapy; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012838:Silymarin / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D012838:Silymarin; D005632:Fructose; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: CSE; Hepatic ischemia-reperfusion; Hydrogen sulphide; Insulin resistance; Silymarin