Injury of mouse brain mitochondria induced by cigarette smoke extract and effect of vitamin C on it in vitro.
OBJECTIVE
To investigate the toxicity of cigarette smoke extract (CSE) and nicotine on mouse brain mitochondria as well as the protective effect of vitamin C in vitro.


METHODS
Mouse brain mitochondria in vitro was incubated with CSE or nicotine in the absence or presence of vitamin C for 60 minutes, and the changes of mitochondrial function and structure were measured.


RESULTS
CSE inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. However, no significant changes in the peroxidation indices were observed when mitochondrial respiratory enzymes activity was inhibited, and protection of mitochondria from CSE-induced injury by vitamin C was not displayed in vitro. The effect of CSE on mouse brain mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. CSE inhibited swelling of mitochondria at 6.5 mumol/L Ca2+, but promoted swelling response at 250 mumol/L Ca2+. Nicotine, the major component of cigarette smoke, showed no significant damage in mouse brain mitochondria in vitro. The CSE treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane appeared to be preserved.


CONCLUSIONS
The toxic effect of CSE on brain mitochondria may be due to its direct action on enzymatic activity rather than through oxygen free radical injury. Nicotine is not the responsible component for the toxicity of CSE to brain mitochondria.
Yang
Yu-Mei
YM
Division of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. yangym@imm.ac.cn
Liu
Geng-Tao
GT
D000251:Adenosine Triphosphatases / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000473:pathology*; D003576:Electron Transport Complex IV / Q000494:pharmacology; D005609:Free Radicals; D005731:Ganglionic Stimulants / Q000633:toxicity*; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D009538:Nicotine / Q000633:toxicity*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D000975:Antioxidants; D005609:Free Radicals; D005731:Ganglionic Stimulants; D012906:Smoke; D009538:Nicotine; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D001205:Ascorbic Acid