Evaluation of the Acute Oral Toxicity Class of Trinuclear Chromium(III) Glycinate Complex in Rat

Chromium(III) is considered as an essential element playing a role in carbohydrate and lipid metabolism, and various chemical forms of this element are widely used in dietary supplements. A new trinuclear chromium(III) glycinate complex [Cr3O(NH2CH2CO2)6(H2O)3]+NO3− (CrGly), an analogue of Cr3 (trinuclear Cr(III) propionate complex) has been synthesized as a potential source of supplementary Cr. In this study, we evaluated the acute toxicity class of CrGly in Wistar rats applying the OECD 423 procedure. Male and female Wistar rats (n = 12, 6 ♀ and 6 ♂) were given by gavage either a single dose of CrGly 2,000 mg/kg body mass (equals to 300 mg Cr(III)/kg body mass; in aqueous solution) or equivalent volumes of distilled water and fed ad libitum commercial Labofeed B diet, and observed carefully for 14 days, then sacrificed to collect blood and internal organs for biochemical and histologic examination. No death cases were detected. No abnormalities in animal behavior, body mass gains, gross organ histology, or blood morphology and biochemistry were observed. The results demonstrate that LD50 of CrGly is greater than 2,000 mg/kg when administrated orally to rat; thus, this compound appears to belong to the fifth category in the GHS system or the fourth class (“unclassified”) in the EU classification system

Trace elements in glucometabolic disorders: an update

Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed

The effect of chromium (III) on fatty acid metabolism and insulin path related gene expression in mouse myocytes cell line C2C12

Jony chromu (III) mają istotny wpływ na przemianę węglowodanowo-lipidową ludzi i zwierząt, powodując u chorych na cukrzycę wzrost wrażliwości komórek na insulinę, zwiększenie przemian kwasów tłuszczowych, spadek masy ciała i poziomu wolnych kwasów tłuszczowych w surowicy. Celem pracy było zbadanie działania chromu na proces beta-oksydacji kwasów tłuszczowych oraz zmiany ekspresji genów szlaku insulinowego w tkance mięśniowej. Do badań użyto mysich komórek mięśniowych linii C2C12 poddanych 4-dniowemu różnicowaniu. Chrom dodawano do medium w postaci chlorku lub pikolinianu chromu a aktywność β-oksydacji mierzono po 1, 3, 6 lub 48 godzinnej inkubacji. Suplementacja chromem w stężeniu 1 μgCr³⁺/L spowodowała wzrost (p < 0,001) aktywności procesu spalania kwasów tłuszczowych w 1, 3 godzinie inkubacji z pikolinianem oraz w 1, 3, i 6 godzinie inkubacji z chlorkiem chromu. Po 48 godzinnej inkubacji z jonami chromu obserwowano obniżenie aktywności tego procesu. Wpływ chlorku chromu 10 μgCr³⁺/L na ekspresję genów zaangażowanych w szlak przekazywania sygnału od insuliny określono z wykorzystaniem mikromacierzy SuperArray. Chrom po 4 godz. inkubacji spowodował wzrost ekspresji 22 genów natomiast po 24 godzinach wzrost dwóch i spadek ekspresji dwóch genów w porównaniu z kontrolą. Uzyskane wyniki wskazują na pozytywny wpływ suplementacji chromem na zwiększenie aktywności β-oksydacji. Dane uzyskane techniką mikromacierzy wskazują na interakcję jonów chromu ze szlakiem przewodzenia sygnału insulinowego również na poziomie transkrypcyjnym. Wzrost ekspresji genów związanych z metabolizmem lipidów i genów docelowych dla PPAR sugerują trwałe efekty wywołane przez jony chromu.Chromium (III) ions influence significantly carbohydrate-lipid metabolism causing in diabetic subjects an optimalisation of insulin action, increase of lipid alteration, decrease body weight and free fatty acids plasma level. The aim of the present study was to describe changes in β-oxidation of fatty acids and gene expression following chromium supplementation. The experiments were performed in mouse myoblast C2C12 cell line over 4 days differentiation. Chromium was added to medium (DMEM), as chromium chloride (CrCl₃) or chromium picolinate, in 1 and 10 μgCr³⁺/L concentrations. Beta-oxidation of fatty acids activity was measured after 1, 3, 6, or 48 h. incubations. Introduction of chromium 1 μgCr³⁺/L to cell culture resulted intensification of fatty acids oxidation after 1 and 3 h (picolinate, p < 0,001) and 1, 3, and 6 h (chloride, p < 0,001) incubation. We observed higher stimulation effect along chromium chloride administration (about 50% of control value) than chromium picolinate (25% of control value). After 48h incubation decrease of fatty acids oxidation were noticed. The influence of chromium chloride (10 μgCr³⁺/L) supplementation on gene expression was examined using microarray SuperArray technique. Chromium added caused increase in 22 genes expression over 4h while only 2 increase and 2 decrease over 24h incubation in compare with control. The results in these studies showed positive effect of chromium supplementation on activity of β-oxidation. Results from microarray analysis indicate chromium interaction on signaling insulin pathway, also on transcription level. Increased expression of genes engaged in lipid metabolism and genes activated by peroxisome proliferator-activated receptor PPAR suggest permanent effect caused by chromium ions