Fatemeh Shaki - Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Iran
Milad Arab-Nozari - Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Iran
Nematollah Ahangar - Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Iran
Mohammad Shokrzadeh - Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Iran
Ebrahim Mohammadi - Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Mazandaran, Iran

Background: The co-existence of various pollutants in environment and food chains is considerably concerned due to the fused impact on environment and public health. Most research and regulations only address the effect of a single pollutant or chemical and exposure to high doses with the potential for toxic effects, but studies conducted using low-dose of multiple contaminants can mimic the true environmental exposure scenario. In this study, we aimed to evaluate the toxicity induced by exposure to non-toxic dose of two environmental pollutants (cadmium and fluoride) as well as involved mechanism.Methods: First, we determined non-toxic doses of cadmium and fluoride in wistar rats and maximum dose that did not showed any significant change compared to control group, was selected as non-toxic dose of pollutant. Then, combination of non-toxic dose of both cadmium and fluoride were used. In addition of biochemical and histopathological evaluation, the role of different pathway including, oxidative stress (ROS, glutathione, lipid peroxidation, SOD, GPX) mitochondrial dysfunction (MMP, swelling and MTT assay), apoptosis (expression of BAX and BCl2 by RT-PCR), inflammation (expression of NF-kb,IL1 and TNF-alpha by RT-PCR) in potentiation of tissue toxicity (renal, liver and testis) were evaluated.Results: Co-exposure to non-toxic dose of both cadmium and fluoride results in significant change in biochemical and pathological parameters related to tissue toxicity. Also, mechanistic evaluation showed that mitochondrial oxidative damage, apoptosis and NF kb inflammatory pathway contributed in additive toxicity effect.Conclusion: This study was premised on the fact that the net toxic manifestations, produced by multiple exposures may be different from those caused by a single agent as a result of their additive, synergistic or antagonistic action.