Enhanced remedial effects for vitamin D3 and calcium co-supplementation against pre-existing lead nephrotoxicity in mice: The roles of renal calcium homeostatic molecules

Background: Lead (Pb) is a toxic heavy metal and nephropathy is common with chronic exposure. Although vitamin D (VD) and calcium (Ca) showed promising protections, their co-administration was not previously investigated in Pb nephrotoxicity. This study measured the potential interactions and remedial effects of VD and/or Ca on established Pb nephropathy. Methods: Fifty adult male mice were equally distributed into: negative controls (NC), positive controls (PC), Ca, VD and VDC groups. The study duration was seven weeks and all groups, except the NC, received Pb acetate in drinking water (500 mg/L) throughout the study. The Ca, VD and VDC groups also received oral Ca (50 mg/kg; five times/week) and/or intramuscular VD (1000 IU/kg; three times/week) from week four till the end of the study. Results: The PC group showed substantial reduction in serum VD, hypocalcaemia, hypercalciuria and proteinuria alongside marked tissue inflammation, oxidative stress and apoptosis/necrosis. Pathological alterations were also detected in the mRNAs and proteins of the VD-metabolising enzymes, receptor and binding protein alongside several Ca-membrane channels, membrane transporters, intracellular binding proteins and mediators. While both monotherapies equally demonstrated moderate improvements, the VDC showed the utmost corrective actions on serum and tissue Pb concentrations, the inflammatory and antioxidative markers, the expressions of renal VD/Ca-molecules and tissue integrity. Moreover, the results were comparable between the VDC and NC groups. Conclusions: This report is the first to reveal potential enhanced remedial outcomes for combining VD and Ca against pre-existing Pb nephrotoxicity and the enhancements could be dependent on Ca-regulatory pathways.