title: Limonin attenuates hepatocellular injury following liver ischemia and reperfusion in rats via toll-like receptor dependent pathway.
abstract: Limonin has been shown to exhibit anti-inflammatory and antioxidant properties in the settings of chemically induced hepatic injury. The current study aimed to investigate the protective effects of limonin on experimentally-induced hepatic ischemia reperfusion (I/R) injury in rats. Rats were injected IP with either DMSO or limonin (100 mg/kg BW), 30 min before submission to 45 min of ischemia, followed by 1 h of reperfusion. Limonin ameliorated the deleterious effects of I/R as indicated by improvement in liver function tests, reduction of lactate dehydrogenase, reduction of oxidative stress, decrease in hepatocyte degeneration, and pyknosis. Furthermore, pretreatment of I/R rats with limonin, induced a significant down regulation in the various elements of the toll like receptor (TLR)pathway including TLR-2 and TLR-4, myeloid differentiation factor 88 (MYD88) and toll/IR-1(TIR)-domain-containing adaptor protein inducing interferon-beta (TRIF) and the downstream effectors TNF-α, TNF-α/IL-10 ratio and nuclear factor-κB (NF-κB). It also increased the anti-inflammatory cytokine IL-10 and decreased the activity of the apoptotic marker, caspase-3. These data indicate that limonin exerts antioxidant and anti-inflammatory effects in ischemic liver, thus, protecting hepatocytes against I/R injury in rats. The mechanism of these hepatoprotective effects appears to be related to the antioxidant and anti-inflammatory potential of limonin mediated by the down regulation of TLR- signaling pathway.
authors: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. Electronic address: mona_pharmacology@yahoo.com.
authors: Mona F
authors: MF
authors: Mahmoud
authors: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors: Samar
authors: S
authors: Gamal
authors: Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors: Hassan M
authors: HM
authors: El-Fayoumi
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D036701:Limonins / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D036701:Limonins; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C523075:Ticam1 protein, rat; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3; C001546:limonin
keywords: I/R; Limonin; Oxidative stress; TLR