Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats

Abstract

This study measured the effects of vitamin D (VD) supplementation on the underlying molecular pathways involved in renal and testicular damage induced by lead (Pb) toxicity. Thirty two adult male Wistar rats were divided equally into four groups that were treated individually or simultaneously, except the negative control, for four weeks with lead acetate in drinking water (1,000 mg/L) and/or intramuscular VD (1,000 IU/kg; 3 days/week). Pb toxicity markedly reduced serum VD and Ca2+, induced substantial renal and testicular injuries with concomitant significant alterations in the expression of VD metabolising enzymes, its receptor and binding protein, and the calcium sensing receptor. Pb also significantly promoted lipid peroxidation and pro-inflammatory cytokines (IL-4 and TNF-α) in the organs of interest concomitantly with declines in several anti-oxidative markers (glutathione, glutathione peroxidase and catalase) and the anti-inflammatory cytokine, IL-10. The co-administration of VD with Pb markedly mitigated renal and testicular injuries compared with positive controls. This was associated with restoration of the expression of VD related molecules, promotion of anti-oxidative and anti-inflammatory markers, but tissue Pb concentrations were unaffected. In conclusion, this report is the first to reveal potential protective effects for VD against Pb-induced renal and testicular injuries via anti-inflammatory and anti-oxidative mechanisms.

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

“…In contrast, stronger antioxidative and anti‐inflammatory effects, enhanced cell viability and more effective regulation of Ca 2+ proteins were detected in the VD group compared with the PC and Ca groups. Our findings advocate that VD 3 could be more advantageous than Ca 2+ in mitigating Cd‐induced hepatic injury, possibly by simultaneously exerting more potent antioxidative, anti‐inflammatory, and Ca 2+ ‐regulatory actions . However, the VDC group showed the supreme protective effects alongside the lowest apoptosis index compared with the monotherapy groups.…”

“…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 .…”

“…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 ) .…”

“…[21,22] Circulatory 25-OH VD is transported reversibly attached to its specific vitamin D-binding protein (VDBP), which is also mainly produced by the liver. [23,24] A final hydroxylation occurs by renal tubular Cyp27b1 enzyme to form active VD (VD 3 ). [23,24] VD 3 initiates its cellular actions by activating its nuclear receptor (vitamin D receptor [VDR]), which is abundantly expressed in hepatic tissues.…”

“…[23,24] A final hydroxylation occurs by renal tubular Cyp27b1 enzyme to form active VD (VD 3 ). [23,24] VD 3 initiates its cellular actions by activating its nuclear receptor (vitamin D receptor [VDR]), which is abundantly expressed in hepatic tissues. [21,22] The bioavailability of active VD 3 is generally regulated in the targeted organs, including the liver, by the Cyp24a1 catalyzing enzyme.…”