Natural terpenes prevent mitochondrial dysfunction, oxidative stress and release of apoptotic proteins during nimesulide-hepatotoxicity in rats

Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpen...

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Veröffentlicht in:	PloS one 2012-04, Vol.7 (4), p.e34200
Hauptverfasser:	Singh, Brijesh Kumar, Tripathi, Madhulika, Chaudhari, Bhushan P, Pandey, Pramod K, Kakkar, Poonam
Format:	Artikel
Sprache:	eng
Schlagworte:	8-Hydroxyguanine Analgesics Animals Antioxidants Antioxidants (Nutrients) Antioxidants - metabolism Apoptosis Apoptosis Regulatory Proteins - secretion Apoptosis-inducing factor Arthritis Bilirubin Biochemistry Biocompatibility Biological Products - pharmacology Biology Biomarkers Camphene Caspase Caspase 3 - metabolism Caspase 9 - metabolism Caspase-3 Caspase-9 Cell Death - drug effects Chemistry Clinical medicine Copper Cytochrome Cytochrome c Cytoprotection - drug effects Damage prevention Deoxyribonucleic acid Depolarization DNA DNA Damage DNA glycosylase DNA-formamidopyrimidine glycosylase Drug dosages Electron Transport - drug effects Endonuclease Enzymatic activity Enzymes Free radicals Gene expression Hepatitis Hepatotoxicity Histochemistry Histopathology Homeostasis Homeostasis - drug effects Inflammation Laboratories Lipid Metabolism - drug effects Liver - cytology Liver - drug effects Liver diseases Macromolecules Male Males Manganese Medicine Membrane permeability Membrane Potential, Mitochondrial - drug effects Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondria - pathology Mitochondria - secretion Molecular modelling NAD Nonsteroidal anti-inflammatory drugs Nucleotides - metabolism Oxidants - metabolism Oxidation resistance Oxidative stress Oxidative Stress - drug effects Oxidizing agents Permeability Permeability - drug effects Proteins Proteolysis - drug effects Rats Rats, Sprague-Dawley RNA Rodents Sulfonamides - toxicity Superoxides Terpenes Terpenes - pharmacology Toxicity Toxicology Transcription, Genetic - drug effects Zinc
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Zusammenfassung:	Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0034200