Bio and Geno-toxic Activities of Cadmium- Arsenic Salts Combination And/or Fluoride in Female Rats Confirmed by Molecular Docking.

Heavy metals are increasingly recognized as major toxic agents and potential carcinogens. This research was designed to assess the biochemical and genetic toxicity that arises from the exposure to a combination of cadmium and arsenic salts and/or fluoride in rats over a period of two months. Additionally, this study examined the molecular interactions of these salts with two crucial target proteins: heat shock protein 70 (HSP70) and metallothionein (MT1) through molecular docking analysis. Rats were divided into four groups. Group 1: rats were administrated sodium fluoride only. Group 2: rats received a combination between cadmium and arsenic salts. Group 3: rats were administrated mixture of the combination between cadmium and arsenic salts in addition to sodium fluoride. Group 4: rats represented the normal control. Biochemical and molecular as well as docking studies in addition to histological examinations were evaluated. Each rat group exhibited unique biochemical findings (in comparison to the control group) that were different from those of the other groups. Noticeable significant alterations in serum thyroid hormones (FT4 and FT3) were found in the group that received only fluoride (F group) associated with a predicted later cardiac dysfunction. Unusual significant reduction in triglyceride levels was observed in the rats treated with the combination of heavy metals (H group) which may contribute to a case of cardiomyopathy. On the other hand, the group receiving the mixture of all three salts (H + F) group showed biochemical results reaching normal levels. Thrombocytosis, characterized by increased platelet counts, was observed in the (F), (H), and (H + F) groups. At the molecular level, the results obtained from the PCR technique indicated that the highest level of damage was observed in the group that received the mixture of heavy metals and fluoride (H + F). This group showed a significantly reduced gene expression of (HSP70) and (MT1) in liver tissues. Docking investigations showed that sodium fluoride, cadmium chloride, and sodium arsenate have unique but complementary binding mechanisms with (HSP70) and (MT1). Sodium fluoride stabilizes connections by hydrogen bonds and hydrophobic contacts, whereas cadmium chloride uses metal coordination and pi-alkyl networks. Sodium arsenate, with its high-affinity hydrogen bonding, further enhances binding stability. Despite achieving normal levels in its specified biochemical parameters, the group exposed to the mixture of heavy metals and fluoride (H + F) experienced more harmful effects and worsened overall health compared to the groups administrated fluoride or heavy metals combination alone. This was attributed to the suppression of essential cellular defense mechanisms and a rise in platelet (PLT) count which in turn lead to an accelerated and increased mortality.