Prenatal exposure to cigarette smoke causes persistent changes in the oxidative balance and in DNA structural integrity in rats submitted to the animal model of schizophrenia

• Published in: Journal of psychiatric research 2011-11, Vol.45 (11), p.1497-1503
• Main Authors: Fraga, Daiane B, Deroza, Pedro F, Ghedim, Fernando V, Steckert, Amanda V, De Luca, Renata D, Silverio, Alexandre, Cipriano, Andreza L, Leffa, Daniela D, Borges, Gabriela D, Quevedo, João, Pinho, Ricardo A, Andrade, Vanessa M, Dal-Pizzol, Felipe, Zugno, Alexandra I
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Animals; Biological and medical sciences; Cigarettes; DNA; DNA - metabolism; DNA Damage; Female; Ketamine; Lipid Peroxidation; Lipids; Male; Medical sciences; Models, Animal; Oxidative stress; Pregnancy; Pregnant smoking; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - physiopathology; Proteins; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Wistar; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - physiopathology; Tobacco Smoke Pollution - adverse effects; Tobacco smoking; Tobacco, tobacco smoking; Toxicology
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2011.06.007

Abstract Epidemiological studies have indicated that prenatal exposure to environmental insults can bring an increased risk of schizophrenia. The objective of our study was to determine biochemical parameters in rats exposed to cigarette smoke (CS) in the prenatal period, evaluated in adult offspring submitted to animal model of schizophrenia induced by acute subanaesthetic doses of ketamine (5 mg/kg, 15 mg/kg and 25 mg/kg). Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day, daily for a period of 28 days. We evaluated the oxidative damage in lipid and protein in the rat brain, and DNA damage in the peripheral blood of male adult offspring rats. To determine oxidative damage in the lipids, we measured the formation of thiobarbituric acid reactive species (TBARS) and the oxidative damage to the proteins was assessed by the determination of carbonyl groups content. We also evaluated DNA damage using single-cell gel electrophoresis (comet assay). Our results showed that rats exposed to CS in the prenatal period presented a significant increase of the lipid peroxidation, protein oxidation and DNA damage in adult age. We can observe that the animals submitted at acute doses of ketamine also presented an increase of the lipid peroxidation and protein oxidation at different doses and structures. Finally, we suggest that exposure to CS during the prenatal period affects two essential cerebral processes during development: redox regulation and DNA integrity, evaluated in adult offspring. These effects can leads to several neurochemical changes similar to the pathophysiology of schizophrenia.