title: Leishmanial lipid affords protection against oxidative stress induced hepatic injury by regulating inflammatory mediators and confining apoptosis progress.
abstract: Persistence of liver injury alters the internal milieu, promotes deregulation of inflammatory factors, and leads to dysplastic lesions like fibrosis, cirrhosis to hepatocellular carcinoma. Our previous study revealed that leishmanial lipid (pLLD) exerts potential anti-inflammatory activity in sepsis associated hepatic injury. We now show that pLLD gives protection against chemical induced hepatotoxicity in murine system. The beneficial effect of treatment with pLLD on such hepatic injury in mice was analyzed using different assays including ELISA, FACS, western blot and immunohistochemical analysis. pLLD significantly suppressed serum enzymes and rectified the histopathological alteration to induce the antioxidant level in CCl4 intoxicated liver. Levels of several growth factors including TGF-β, HGF, and EGF were significantly improved in serum and hepatic tissue with consequent reduction of caspase activities and expressions of Bad, Bax, p53, and NF-κBp65. Moreover, pLLD modulated inflammatory responses by decreasing the production of several cytokines and chemokines, thus preventing the infiltration of immune cells to the damaged area. It accelerated the repair process in liver damage with modulation of signalling cascade via alteration of apoptotic factors. Our experimental approaches suggest that pLLD effectively prevents liver injury mainly through down regulation of oxidative stress and inflammatory response towards anti-apoptotic changes.
authors.affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India.
authors.forename: Nabanita
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Das
authors.affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India.
authors.forename: Dipayan
authors.initials: D
authors.lastname: Bose
authors.affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India.
authors.forename: Somenath
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata 700032, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
authors.affiliation: Cancer Biology & Inflammatory Disorder Division, CSIR - Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India. Electronic address: krishnaiicb@yahoo.com.
authors.forename: Krishna Das
authors.initials: KD
authors.lastname: Saha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D022781:Hepatocytes / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D007893:Leishmania donovani / Q000737:chemistry* / Q000166:cytology*; D008055:Lipids / Q000737:chemistry / Q000627:therapeutic use*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids
keywords: Apoptosis; Inflammation; Leishmania; Lipid; Liver injury; Oxidative stress