Table 1.

Antioxidant compounds used in CHO cells to reduce oxidative stress

Component	Way of action described in literature	Effect observed	References
Thiol compounds
Glutathione	ROS scavenger Substrate for ROS scanvenger enzymes Maintain high mitochondria potential	Decrease cell death Increase titer	Yun et al. (2001, 2003)
N‐acetylcysteine and N‐acetylcysteine amine	ROS scavenger Increase of intracellular glutathione pool	Decrease cell death Increase titer Impact on sialylation	Chang et al. (1999); Ercal, Treeratphan, Lutz, Hammond, and Matthews (1996); Issels, Nagele, Eckert, and Wllmanns (1988); Oh et al. (2005); Tanel and Averill‐Bates (2007); Wu et al. (2008)
S‐sulfocysteine	Stabilized cysteine Up regulation of SODs transcription Increase of intracellular glutathione pool	Decrease cell death Increase titer Decrease recombinant protein fragments level Decrease recombinant protein trisulfides level	Hecklau et al. (2016); Seibel et al. (2017)
Thiazolidine	Stabilization of the cell culture media Up regulation of SODs transcription Increase of intracellular glutathione pool	Decrease cell death Increase titer	Kuschelewski et al. (2017)
Taurine and it precursors	Increase of intracellular glutathione pool Reduce lipid peroxidation Reduce catalase and erythrocyte G6PD activity Reduce mitochondrial superoxide generation	Decrease cell death	Aruoma et al. (1988); Gurer et al. (2001); Jong, Azuma, and Schaffer (2012)
Lipoic acid	ROS scavenger Iron and copper chelator	Decrease cell death	Gurer et al. (1999); Maharjan et al. (2016)
α Ketoacids
Pyruvate	ROS scanvenger	Decrease cell death Decrease recombinant protein trisulfides level	Andrae et al. (1985); Kshirsagar, McElearney, Gilbert, Sinacore, and Ryll (2012); Long and Halliwell (2009)
α‐Ketoglutarate	ROS scanvenger Iron chelator	Decrease cell death	Andrae et al. (1985); Bayliak, Lylyk, Vytvytska, and Lushchak (2016)
Vitamins
Ascorbic acid and derivative	ROS scavenger	Decrease cell death Increase titer	Yun et al. (2001)
α‐Tocopherol	Lipid peroxyl radical scavenger	Decrease cell death	Chepda, Cadau, Chamson, Alexandre, and Frey (1999); Murati et al. (2017)
Trace elements
Selenium/selenocysteine	Cofactor of antioxidant enzymes Regulate expression of glutathione peroxidase	Decrease cell death	Aykin‐Burns an Ercal (2006); Gasser, Mulsant, and Gillois (1985); Hamilton and Ham (1977); Weiss and Sunde (1997)
Chelators
Defroxamine	Iron chelator	Decrease cell death	Yun et al. (2003)
Aurintricarboxylic acid	Iron chelator	Decrease cell death	Tabuchi, Sugiyama, Tanaka, and Tainaka (2010)
Polyamines	Iron chelator	Decrease cell death Increase titer	Gaboriau et al. (2004); Lovaas (1997)
Phenolic compounds
Butylated hydroxyanisole	ROS scavenger Iron chelator	Decrease cell death Increase titer	Malhotra et al. (2008)
Baicalein	ROS scavenger	Increase titer	Ha et al. (2017); Hamada, Hiramatsu, Edamatsu, and Mori (1993)
Epicatechin gallate	ROS scavenger	Decrease recombinant protein charge variants level	Hossler et al. (2015)
Rutin	ROS scavenger	Decrease recombinant protein charge variants level	Hossler et al. (2015)

Abbreviations: CHO, Chinese hamster ovary; ROS, reactive oxygen species; SOD, sodium oxide dismutase.