Influence of ferulic acid on nicotine-induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine.
We examined the effect of ferulic acid (FA), a naturally occurring phenolic compound on lipid peroxidation and endogenous antioxidant status, DNA damage and inflammation in nicotine-administered Wistar rats. The effect of FA against nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known antioxidant. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and FA and NAC were given simultaneously by intragastric intubation for 22 weeks. Seventy two Wistar rats were divided into six groups: (i) control, (ii) nicotine, (iii) nicotine+FA (iv), nicotine+NAC, (v) FA and (vi) NAC. At the end of the experimental period, cellular damage was assessed by measuring the activities of lactate dehydrogenase and alkaline phosphatase in plasma, which were significantly elevated in nicotine-administered rats when compared with control group. Enhanced lipid peroxidation (evaluated by measuring the thiobarbituric acid reactive substances and hydroperoxides) was accompanied by a significant decrease in the endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione in circulation, lung and liver of nicotine-treated rats when compared with control group. DNA single strand breaks (evaluated by comet assay) and frequency of micronuclei were significantly increased in peripheral blood of nicotine-treated rats when compared with control. Our Western blot analysis showed a significant increase in the expression of cyclooxygenase-2 and NF-kappaB in lung and liver of nicotine-treated rats. FA and NAC co-treated rats showed a significant decrease in the activities of circulatory lactate dehydrogenase and alkaline phosphatase, the levels of lipid peroxidative markers (in circulation, lung and liver), DNA single stranded breaks (comet parameters), micronuclei frequency (in the whole blood) and expression of cyclooxygenase-2 and Nf-kappaB (in lung and liver tissues), and significant increase in antioxidant status (in circulation, lung and liver). The protection of FA against nicotine-induced toxicity was merely equal to the effect of NAC. FA and NAC treatment alone did not produce any damage to control rats. Thus, we propose that FA exerts protective effect against nicotine toxicity by modulating the lipid peroxidation, inflammation, DNA damage and endogenous antioxidant status.
Sudheer
Adluri Ram
AR
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608002, Tamil Nadu, India.
Muthukumaran
Shanmugavel
S
Devipriya
Nagarajan
N
Devaraj
Halagowder
H
Menon
Venugopal P
VP
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D020552:Comet Assay; D003373:Coumaric Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D007441:Intubation, Gastrointestinal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D003373:Coumaric Acids; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D009538:Nicotine; C004999:ferulic acid; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D005978:Glutathione; D000111:Acetylcysteine