Comparative Biochemistry and Physiology Part C 135 (2003) 331–336 1532-0456/03/$ - see front matter  2003 Elsevier Inc. All rights reserved. doi:10.1016/S1532-0456(03)00120-0 Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva Mohammad Abdollahi*, Arezou Bahreini-Moghadam, Bita Emami, Fatemeh Fooladian, Khatereh Zafari Department of Toxicology and Pharmacology, Tehran University of Medical Science, Tehran 14155-6451, Iran Received 28 January 2003; received in revised form 28 May 2003; accepted 29 May 2003 Abstract The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mgykg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mgykg) and sildenafil (5 mgykg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors.  2003 Elsevier Inc. All rights reserved. Keywords: Cadmium; Submandibular; Rat; cAMP; cGMP; Oxidative stress; Saliva; Sildenafil; Theophylline; Phosphodiesterase inhibitor 1. Introduction Cadmium occurs in nuclear industries, alkaline storage batteries, as amalgam in dentistry and as stabilizer for polyvinyl chloride. Cadmium is con- sidered to have no biological function and is highly toxic to both animals and humans. Exposure to cadmium via food and drinking water is an impor- tant route in the general population (Nath et al., *Corresponding author. Tel.: q98-9112710860; fax: q98- 21-6461178. E-mail address: mohammad.abdollahi@utoronto.ca (M. Abdollahi). 1984; Abdollahi et al., 1998a,b; Brzoska and Moniuszko-Jakoniuk, 1998). Cadmium is a trace metal that progressively accumulates in the body. The saliva consists of water, electrolytes, pro- teins and enzymes secreted from salivary glands under control of autonomic nervous system. Improper secretion of proteins and electrolytes from salivary glands not only disturbs oral health, but also influence all body function especially the gastrointestinal tract (Edgar, 1992; Sreebny, 2000; Abdollahi and Radfar, 2003). Inhibitory effects of cadmium on submandibular gland function and secretion of proteins, enzymes and electrolytes has been recently reported. It could be prevented by pretreatment of animals with L-arginine, a nitric