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

Vitamin D3 and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti‐inflammatory actions by remodeling cellular calcium pathways

“…Moreover, VD 3 controls many cellular Ca 2+ ‐regulatory molecules including VDCCs, SOCs, and CAM‐CAMKII . VD 3 is also a potent anti‐inflammatory and antioxidative hormone that has been shown to efficiently modulate many of the oxidative stress and the inflammatory pathways involved in Cd‐induced cell damage . Therefore, we speculate that the dysregulation of the hepatic VD system could have created a biased molecular milieu by which Cd facilitated its influx into the hepatocyte, oxidative stress, and inflammation under the umbrella of hypovitaminosis D and dyshomeostasis of hepatic Ca 2+ molecules .…”

“…Hence, the total therapeutic and nutritional amounts of VD 3 (357.1 IU/kg/d) and elemental Ca 2+ (211.4 mg/kg/d) delivered to the VD, Ca, and VDC groups were equal to the daily human doses of 57.6 IU/kg for VD 3 and 34.1 mg/kg for Ca 2+ as per the equation for dose conversion between rat and human . The used doses were double the daily human requirements for VD 3 (29.1 IU/kg) and Ca 2+ (16.7 mg/kg) for an adult of 60 kg body weight as previously described . After overnight fasting, euthanasia was done on the first day of the fifth week for all groups by cervical dislocation under anesthesia (90 mg/kg Ketamine HCl [Pfizer Inc, NY] and 3 mg/kg xylazine [Rompun 2% wt/vol; Bayer Animal Health, Monheim, Germany]).…”

“…The membranes were developed with Pierce ECL Plus‐kit (#32132; Thermo Fisher Scientific) and the images were acquired by a ChemiDoc XRS+ System (Bio‐Rad Laboratories Inc). The band densitometry for each targeted protein was quantified by the ImageJ software (https://imagej.nih.gov/ij/), and the results were normalized against the corresponding GAPDH band, as previously described …”

“…The main systemic form of VD, 25‐hydroxy vitamin D (25‐OH VD), is synthesized by the hepatic microsomal Cyp2R1 and mitochondrial Cyp27a1 hydroxylases . Circulatory 25‐OH VD is transported reversibly attached to its specific vitamin D‐binding protein (VDBP), which is also mainly produced by the liver . A final hydroxylation occurs by renal tubular Cyp27b1 enzyme to form active VD (VD 3 ) .…”

“…However, none of the previous studies either measured the effects of Cd on the hepatic expression of VD‐regulatory molecules or explored the protective antioxidative and anti‐inflammatory actions of the hormone. Moreover, numerous clinical and experimental studies have revealed enhanced antioxidative and anti‐inflammatory effects for cosupplementing VD 3 and Ca 2+ against a diversity of diseases . Therefore, this study was designed to measure the potential interplays between hepatic VD/Ca 2+ ‐regulatory molecules with chronic Cd toxicity in addition to the potential protective actions of VD 3 and/or Ca 2+ supplementations against Cd hepatotoxicity.…”