Impact of oral cadmium intoxication on levels of different essential trace elements and oxidative stress measures in mice: a response to dose

Abstract

The study evaluated the effect of oral intoxication of cadmium and the possible causes of oxidative stress and its preferential accumulation in different organs as well as sub-sequential effects in mice. Twenty-four Swiss albino male mice were divided into three groups viz., normal control group without cadmium chloride (CdCl), whereas a daily dose of 0.5 and 1.2 mg of CdCl was orally administered for a period of a week to dose group 1 (DG-1) and dose group 2 (DG-2), respectively. A significant increase in the severity of cadmium toxicity was observed in animals as evidenced by aggravation in liver enzymes viz., serum alanine aminotransferase and aspartate transaminase, whereas lower levels of antioxidative stress markers in liver and kidney tissues of treated mice were observed as compared to normal control group. A significant depletion of calcium levels in liver tissues of DG-1 (217.36 ± 1.73 μg/g of wet tissues) and DG-2 (186.41 ± 1.56 μg/g of wet tissues) groups, along with Cd accumulation, was observed. To summarize, the current study would increase our understanding with respect to dose-dependent absorption of Cd and its toxicity led to mortality as well as adverse health effects in the body of mice. Graphical abstract ᅟ.

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

“…Another construal could be that systemic and hepatic VD dyshomeostases are extra distressing processes adding to the complexity of the pathogenesis of Cd‐induced liver injury. In this context, Cd‐intestinal absorption and toxic effects were more severe with VD 3 and Ca 2+ deficiency, and hepatic tissue Ca 2+ levels were diminished with chronic Cd toxicity . The trafficking of Cd across intestinal and renal cellular barriers also coincided with inhibitions of several VD‐dependent Ca 2+ ‐transporting proteins and it was suggested that Cd promoted its gathering by causing enterocytes absorption hindrance and excessive renal excretion of Ca 2+ .…”

“…[6] In this respect, Cd pervaded into the targeted cells through the T-type VDCC [9,11] and concomitantly inhibited the L-type channel [12,13] to block [Ca 2+ ] E influx, [43,44] thus resulted in dose-dependent declines in rodent liver Ca 2+ levels. [35,45] Moreover, Cd provoked marked increment in [Ca 2+ ] C by releasing [Ca 2+ ] I from the ER subsequent to the activation of ITPR1 and RYR1. [46,47] Sustained oscillations in [Ca 2+ ] C may then prompt mitochondrial damage and ROS formation by the CAM-CAMKIIα and/or S100B pathways [10,16,17] that could later initiate cell death by ejecting mitochondrial Cyt_C, which binds Casp-9 to activate the chief executor of apoptosis, Casp-3.…”

“…In this context, Cdintestinal absorption and toxic effects were more severe with VD 3 [28] and Ca 2+ [29] deficiency, and hepatic tissue Ca 2+ levels were diminished with chronic Cd toxicity. [35,45] The trafficking of Cd across intestinal and renal cellular barriers also coincided with inhibitions of several VDdependent Ca 2+ -transporting proteins and it was suggested that Cd promoted its gathering by causing enterocytes absorption hindrance and excessive renal excretion of Ca 2+ . [31][32][33] Moreover, VD 3 controls many cellular Ca 2+ -regulatory molecules including VDCCs, SOCs, and CAM-CAMKII.…”

“…Cd also deterred the activities of the Cyp27b1 enzyme and VDR, thus inhibiting the actions of VD 3 . While Ca 2+ and VD 3 replenishments inhibited Cd‐intestinal uptake and enhanced its renal excretion, higher Ca 2+ intake also counteracted Cd‐induced oxidative stress and inflammation . 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.…”

“…While Ca 2+ and VD 3 replenishments inhibited Cd-intestinal uptake and enhanced its renal excretion, [31][32][33] higher Ca 2+ intake also counteracted Cd-induced oxidative stress and inflammation. [34,35] 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.…”