title: Protein dependent fate of hepatic cells under nicotine induced stress and curcumin ameliorated condition.
abstract: Nicotine is mainly metabolized in liver. Its abuse elicits acute phase response by activating macrophages to produce pro-inflammatory cytokines, which play critical role in apoptosis or cell proliferation. The protective pharmacological mechanism of curcumin against nicotine-induced toxicity on protein malnourished liver is still remaining unclear. This study investigated the ameliorative mechanism of curcumin against nicotine-induced toxicity and also fate of liver particularly under protein restricted condition. Female Albino-rats maintained under normal/protein-restricted diets, were subcutaneously injected with nicotine tartrate (2.5 mg/kg body weight/day) and orally supplemented with curcumin (80 mg/kg body weight/day) for 21 days. The animals were then sacrificed to dissect out liver and proceed with further experiments. Interactions of nicotine with DNA both in vivo and in vitro were observed by thermal denaturation and DNA laddering assays. Effects of nicotine on hepatic cells were monitored by differential staining, comet assay, cytokine profiling, mRNA and protein expression. Nicotine caused more intense DNA damage, promoted hepatic cell death through up-regulating pro-apoptotic proteins and signaling molecules in protein malnourished individuals. Through up-regulation of anti-apoptotic proteins and proliferation promoting molecules, nicotine dysregulated homeostasis in normal protein condition. Curcumin significantly ameliorated the nicotine-induced toxicity in both conditions and regulated the imbalance between cell survival and death induced by nicotine. The protein content present in the nicotine induced hepatic cell decides either cell-survival pathway or cytotoxic pathway.
authors.affiliation: Department of Physics, Jadavpur University, Raja S.C. Mullick Road, Kolkata-700032, India.
authors.forename: Satyam
authors.initials: S
authors.lastname: Banerjee
authors.forename: Krishna
authors.initials: K
authors.lastname: Chattopadhyay
authors.forename: Jasmeet Kaur
authors.initials: JK
authors.lastname: Chhabra
authors.forename: Brajadulal
authors.initials: B
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001481:Basal Metabolism / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood / Q000235:genetics; D018736:DNA Adducts / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D004044:Dietary Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044366:Transition Temperature / Q000187:drug effects
chemical_list: D016207:Cytokines; D018736:DNA Adducts; D004044:Dietary Proteins; D011506:Proteins; D014157:Transcription Factors; D009538:Nicotine; D003474:Curcumin