**Conflict of interest**

*Trace Metals in the Environment - New Approaches and Recent Advances*

cells) in a medium containing chromium(III) solution (10<sup>−</sup><sup>6</sup>

molecule 1 messenger ribonucleic acid (ICAM-1 mRNA) [170].

soluble chromium released from the implants.

**5. Conclusions**

species in many systems.

**Acknowledgements**

Several studies have shown that chromium(III), in a certain condition, could improve cutaneous wound either in normal or diabetic Wistar rats using a single dose of a combination of zinc(II) (1.5 mg/kg weight) and chromium(III) (0.02 mg/kg weight) [164] and C57BL6/J mice using chromium(III) chloride (80 μg/kg weight/ day) for 21 days [16]. The mechanism of this effect has not been fully elucidated yet, but it may be related to chromium(III) activity in increasing insulin sensitivity, insulin-like growth factor 1 (IGF-1) serum concentration, and protein deposition [16, 165]. In this case, high glucose concentration could inhibit proliferation and differentiation of skin keratinocytes [166] and increase the stiffness of collagen [167] which further inhibits wound healing. In healing acetic acid-induced colitis wound, chromium(III) also acted as an anti-inflammatory agent by inhibiting several inflammatory markers and downregulating pro-inflammatory cytokine genes and antioxidant by suppressing oxidative stress without any significant side effect [168]. In different situations, the use of chromium-based skin clips [169] and orthopedic implant [74] gave an adverse effect by delaying surgery wound healing process. These cases represented a hypersensitivity effect as a manifestation of systemic contact dermatitis. In vitro study using human skin keratinocyte cell line (HaCaT

chromium(III) ions can decrease wound closure rate and be further decreased when the medium was replaced with another chromium(III) ion-containing medium [170]. Chromium(III) ions also caused downregulation of toll-like receptor-2, -4, and -9 messenger ribonucleic acids (TLR-2, -4, and -9 mRNA), upregulation of matrix metalloproteinase 2 and 13, and upregulation of intercellular adhesion

There's no exact explanation for these opposite effects. However, it may be related to the local concentration of chromium species in wound location. An enhancing effect of wound healing was obtained by applying a relatively small concentration of chromium species via oral administration. In human, for instance, there is only 2% of oral chromium(III) that will be absorbed through stomach and intestine and distributed throughout the body. In the same time, an adverse effect was obtained when local chromium concentration was high due to a particulate and

Chromium as versatile heavy metals showed contradictive properties dealing with its dermatologic toxicity and biological activity properties. The main factors that probably correlate to these properties are concentrations and species of chromium. Significant increment of local chromium concentration (more than 1 ppm for chromium[VI] species) either from dermal or systemic administration would increase the risk of dermatologic toxicities, while topical or oral administration of small recommended dietary concentration of chromium (50–200 μg for chromium picolinate) would give several beneficial effects. More studies need to be conducted to know the exact effect of the local concentration of corresponding chromium

The financial support from Ministry of Research, Technology and Higher Education of the Republic of Indonesia who has funded the research in calixarene-

and resorcinarene-based heavy metal adsorbents is acknowledged.

M) showed that

**132**

The authors state that there is no conflict of interest.
