Cadmium (Cd) is a toxic metal that damages bone tissue by affecting its mineral and organic components. The organic matrix is mainly (90%) composed of collagen, which determines the biomechanical strength of bone. The aim of this study was to evaluate the effect of zinc (Zn) supplementation (30 or 60 mg l ) under moderate and relatively high exposure to Cd (5 and 50 mg l ) on collagen in the rat tibia proximal epiphysis and diaphysis (regions abundant in trabecular and cortical bone, respectively). Significant decrease in collagen type I biosynthesis was found in both regions of the tibia in Cd-treated rats, whereas the supplementation with Zn provided significant protection against this effect. Western blot confirmed the presence of the major type I collagen in the tibia epiphysis and diaphysis, but collagen type II was revealed only in the epiphysis. Acetic acid- and pepsin-soluble collagen concentration in the tibia epiphysis and diaphysis was significantly increased due to the exposure to Cd, whereas the supplementation with Zn protected, partially or totally, from these effects, depending on the used concentration. The supplementation with Zn also provided protection from unfavorable Cd impact on the maturation of the bone collagen, as the ratio of cross-links to monomers was higher compared to the Cd-treated group. This report confirms our previous findings on the preventive action of Zn against harmful effects of Cd on bone, but additionally, and to the best of our knowledge for the first time, explains the possible mechanism of the beneficial influence of this bioelement.

The mechanism for differential effects of human immune deficiency virus protease inhibitors (HIVPIs), nelfinavir (NEL) and indinavir (IND) on collagen metabolism disturbances was studied in human skin fibroblasts. It has been considered that HIVPIs‐dependent deregulation of collagen biosynthesis involves prolidase (an enzyme providing proline for collagen biosynthesis), glutamine (Gln) (a substrate for proline biosynthesis), nuclear factor‐κB (NF‐κB) (a transcription factor that inhibit expression of type I collagen genes), β1 integrin receptor and Akt signalling. It was found that NEL impaired collagen biosynthesis and the process was more pronounced in the presence of Gln, while IND stimulated collagen biosynthesis. NEL‐dependent inhibition of collagen biosynthesis was accompanied by massive intracellular accumulation of type I collagen, while IND slightly induced this process. This effect of NEL was reversed by ascorbic acid but not N‐acetylcysteine. The mechanism for the NEL‐dependent defect in collagen metabolism was found at the level of prolidase activity, β1 integrin signalling and NF‐κB. NEL inhibited expression of β1 integrin receptor, Akt and ERK1/2 and increased expression of p65 NF‐κB. However, inhibitors of p65 NF‐κB did not prevent NEL‐dependent inhibition of collagen biosynthesis suggesting that this transcription factor is not involved in studied mechanism. Using PI3K inhibitor wortmannin that prevent phosphorylation of Akt revealed that NEL‐dependent inhibition of Akt results in inhibition of collagen biosynthesis. The data suggest that differential effect of NEL and IND on collagen metabolism involves NEL‐dependent down‐regulation of Akt signalling and proline availability for collagen biosynthesis.

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