title: Ethanol induced hepatic mitochondrial dysfunction is attenuated by all trans retinoic acid supplementation.
abstract: OBJECTIVE
  Alcoholics have reduced vitamin A levels in serum since vitamin A and ethanol share the same metabolic pathway. Vitamin A supplementation has an additive effect on ethanol induced toxicity. Hence in this study, we assessed the impact of supplementation of all trans retinoic acid (ATRA), an active metabolite of vitamin A on ethanol induced disruptive alterations in liver mitochondria.
  
  
  METHODS
  Male Sprague Dawley rats were grouped as follows: I: Control; II: Ethanol (4 g/kg b.wt./day); III: ATRA (100 μg/kg b.wt./day); and IV: Ethanol (4 g/kg b.wt./day)+ATRA (100 μg/kg b.wt./day). Duration of the experiment was 90 days, after which the animals were sacrificed for the study. The key enzymes of energy metabolism, reactive oxygen species, mitochondrial membrane potential and hepatic mRNA expressions of Bax, Bcl-2, c-fos and c-jun were assessed.
  
  
  RESULTS
  Ethanol administration increased the reactive oxygen species generation in mitochondria. It also decreased the activities of the enzymes of citric acid cycle and oxidative phosphorylation. ATP content and mitochondrial membrane potential were decreased and cytosolic cytochrome c was increased consequently enhancing apoptosis. All these alterations were altered significantly on ATRA supplementation along with ethanol. These results were reinforced by our histopathological studies.
  
  
  CONCLUSIONS
  ATRA supplementation to ethanol fed rats, led to reduction in oxidative stress, decreased calcium overload in the matrix and increased mitochondrial membrane potential, which might have altered the mitochondrial energy metabolism and elevated ATP production thereby reducing the apoptotic alterations. Hence ATRA supplementation seemed to be an effective intervention against alcohol induced mitochondrial dysfunction.
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India.
authors.forename: Saritha S
authors.initials: SS
authors.lastname: Nair
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India.
authors.forename: P
authors.initials: P
authors.lastname: Prathibha
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Rejitha
authors.affiliation: Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India. Electronic address: indiramadambath@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Indira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000494:pharmacology; D002952:Citric Acid Cycle / Q000187:drug effects; D019587:Dietary Supplements; D000431:Ethanol / Q000009:adverse effects* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000009:adverse effects / Q000494:pharmacology*; D014801:Vitamin A / Q000009:adverse effects / Q000494:pharmacology; D014815:Vitamins / Q000009:adverse effects / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; C494828:Bax protein, rat; D002492:Central Nervous System Depressants; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014815:Vitamins; D051028:bcl-2-Associated X Protein; D014801:Vitamin A; D000431:Ethanol; D014212:Tretinoin
keywords: ATRA; CYP2E1; Energy metabolism; Ethanol; Mitochondrial membrane potential; Reactive oxygen species