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Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences research Centre, Tehran University of Medical Science, Tehran 141556451, Iran mohammad.abdollahi{at}utoronto.ca

Fatemeh Fooladian

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences research Centre, Tehran University of Medical Science, Tehran, Iran

Bita Emami

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences research Centre, Tehran University of Medical Science, Tehran, Iran

Khatereh Zafari

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences research Centre, Tehran University of Medical Science, Tehran, Iran

Arezou Bahreini-Moghadam

Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences research Centre, Tehran University of Medical Science, Tehran, Iran

The role of oxidative stress in lead toxicity has been proposed in many organs, however, no study has been performed in the salivary glands, which are important parts of the gastrointestinal tract with a high implication in health of the whole body. Recently, it has been proposed that increasing the levels of cGMP and cAMP in the cells may protect from the neurotoxicity of lead. The objective of this study was to determine the ability of lead acetate to produce oxidative stress in rat submandibular as the main salivary gland of the body and to study the role of pretreatment by specific phosphodiesterase inhibitors in the prevention of oxidative stress. Lead acetate (100 mg/kg), alone or in combination with theophylline (25 mg/kg) and sildenafil (5 mg/kg), was administered intraperitoneally to rats. After 2 hours and under general anaesthesia, the submandibular gland ducts were cannulated intraorally using microcannula, and pure saliva was collected for 30 min using pilocarpine (8 mg/kg) as a secretagogue. The submandibular glands were then isolated free under surgery. Oxidative stress in the gland and pure saliva were evaluated measuring lipid peroxidation (thiobarbituric acid reactive substances assay), total thiol groups content and total antioxidant capacity (the ferric reducing ability assay). Results showed significant oxidative stress in the gland and secretions as indicated by increased lipid peroxidation, decreased total antioxidant capacity and thiol group levels. The use of cAMP and cGMP phosodiesterase inhibitors, theophylline and sildenafil, prevented leadinduced increased lipid peroxidation and also protected from decreased thiol groups content and total antioxidant power of the gland and secretions. The same trend of effects was observed in gland and saliva. It is concluded that lead toxicity is mediated through oxidative stress in salivary glands, while increasing intracellular cAMP and cGMP levels may prevent lead-induced oxidative stress.

Key Words: cAMP • cGMP • lead • oxidative stress • rat • saliva • salivary gland

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