Corneal damage and lacrimal gland dysfunction in a smoking rat model

Akihiro Higuchi, Kaori Ito, Murat Dogru, Masanori Kitamura, Fumiko Mitani, Tetsuya Kawakita, Yoko Ogawa, Kazuo Tsubota

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Smoking is a serious public health problem around the world and causes many diseases such as chronic obstructive pulmonary disease, lung cancer, and some eye diseases. Cytochrome P450s (CYPs) are xenobiotic-metabolizing enzymes and are distributed in the corneas, protecting the ocular surface against chemical compounds in the environment. Although CYPs are principally detoxification enzymes, CYP1A1 and CYP2A6 are known to participate in the induction of lung cancer by smoking. We studied the participation of CYPs in corneal dysfunction caused by exposure to mainstream cigarette smoke (MCS) in a smoking rat model. Six-week-old male Sprague-Dawley rats were exposed to MCS. Exposure to MCS caused corneal damage and lacrimal gland dysfunction. Immunohistochemical analysis revealed that CYP1A1 expression was upregulated in the corneal epithelium and ducts of the lacrimal glands, accompanied by an increase in production of reactive oxygen species (ROS). An increase in 8-hydroxy-2′- deoxyguanosine, which is a marker of oxidative DNA damage, was detected only in areas where CYP1A1 was expressed, whereas the level of hexanoyl-lysine adduct, which is an initial marker of oxidative damage of phospholipids, did not increase. Exposure to MCS damaged the corneas and lacrimal glands probably through DNA oxidation by ROS produced by CYP1A1. Although the influence of other components in MCS remains unclear, CYPs, especially CYP1A1, probably participate in corneal damage and lacrimal gland dysfunction induced by smoking.

Original languageEnglish
Pages (from-to)2210-2216
Number of pages7
JournalFree Radical Biology and Medicine
Issue number12
Publication statusPublished - 2011 Dec 15
Externally publishedYes


  • Cytochrome P450
  • Free radicals
  • Lacrimal gland
  • Ocular surface
  • Oxidative stress
  • Smoking

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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