Ultrastructural damage in chromium picolinate-treated cells: A TEM study

Kevin R. Manygoats, Monica Yazzie, Diane M Stearns

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Chromium picolinate (CrPic) is a human dietary supplement that provides a bioavailable form of chromium(III). Its mechanism of action is unknown, and a number of toxic endpoints have been attributed to its use. Understanding the cellular effects of CrPic is important for confirmation or dismissal of these potential toxic effects. The purpose of this work was to characterize morphological damage caused by CrPic, picolinic acid, and chromic chloride in Chinese hamster ovary AA8 cells. A 48-h exposure to 80 μg/cm2 CrPic (0.44 mg/mL CrPic) produced 45% survival by colony formation. Transmission electron microscopy (TEM) showed 83% of analyzed cells having swollen mitochondria with degraded cristae. Apoptosis was identified by nuclear convolution and fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence microscopy with acridine orange/ethidium bromide staining. At the 80 μg/cm2 dose of CrPic, 37% of the cells were apoptotic cells at 48 h. An equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM induced 49% cell survival, and damaged 86% of the mitochondria, with 51% of the cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71% cell survival, and damaged 86% of the mitochondria, with 22% of the cells undergoing apoptosis. The amount of apoptosis correlated with overall cell survival by colony formation, but not with the amount of mitochondrial damage. The coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of Cr(III) to make chromium picolinate a toxic form of Cr(III).

Original languageEnglish (US)
Pages (from-to)791-798
Number of pages8
JournalJournal of Biological Inorganic Chemistry
Volume7
Issue number7-8
DOIs
StatePublished - 2002

Fingerprint

Transmission Electron Microscopy
Cells
Transmission electron microscopy
Mitochondria
Apoptosis
Poisons
Cell Survival
Dietary supplements
picolinic acid
Acridine Orange
Ethidium
Fluorescence microscopy
Chromium
Blister
Dietary Supplements
Cricetulus
Convolution
Fluorescence Microscopy
Ovary
Cell Count

Keywords

  • Apoptosis
  • Chromium picolinate
  • Electron microscopy
  • Mitochondrial damage

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Ultrastructural damage in chromium picolinate-treated cells : A TEM study. / Manygoats, Kevin R.; Yazzie, Monica; Stearns, Diane M.

In: Journal of Biological Inorganic Chemistry, Vol. 7, No. 7-8, 2002, p. 791-798.

Research output: Contribution to journalArticle

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abstract = "Chromium picolinate (CrPic) is a human dietary supplement that provides a bioavailable form of chromium(III). Its mechanism of action is unknown, and a number of toxic endpoints have been attributed to its use. Understanding the cellular effects of CrPic is important for confirmation or dismissal of these potential toxic effects. The purpose of this work was to characterize morphological damage caused by CrPic, picolinic acid, and chromic chloride in Chinese hamster ovary AA8 cells. A 48-h exposure to 80 μg/cm2 CrPic (0.44 mg/mL CrPic) produced 45{\%} survival by colony formation. Transmission electron microscopy (TEM) showed 83{\%} of analyzed cells having swollen mitochondria with degraded cristae. Apoptosis was identified by nuclear convolution and fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence microscopy with acridine orange/ethidium bromide staining. At the 80 μg/cm2 dose of CrPic, 37{\%} of the cells were apoptotic cells at 48 h. An equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM induced 49{\%} cell survival, and damaged 86{\%} of the mitochondria, with 51{\%} of the cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71{\%} cell survival, and damaged 86{\%} of the mitochondria, with 22{\%} of the cells undergoing apoptosis. The amount of apoptosis correlated with overall cell survival by colony formation, but not with the amount of mitochondrial damage. The coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of Cr(III) to make chromium picolinate a toxic form of Cr(III).",
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AB - Chromium picolinate (CrPic) is a human dietary supplement that provides a bioavailable form of chromium(III). Its mechanism of action is unknown, and a number of toxic endpoints have been attributed to its use. Understanding the cellular effects of CrPic is important for confirmation or dismissal of these potential toxic effects. The purpose of this work was to characterize morphological damage caused by CrPic, picolinic acid, and chromic chloride in Chinese hamster ovary AA8 cells. A 48-h exposure to 80 μg/cm2 CrPic (0.44 mg/mL CrPic) produced 45% survival by colony formation. Transmission electron microscopy (TEM) showed 83% of analyzed cells having swollen mitochondria with degraded cristae. Apoptosis was identified by nuclear convolution and fragmentation, and cytoplasmic blebbing. Apoptosis was quantified by fluorescence microscopy with acridine orange/ethidium bromide staining. At the 80 μg/cm2 dose of CrPic, 37% of the cells were apoptotic cells at 48 h. An equivalent dose of picolinate, 3 mM, was much more cytotoxic and thus there was an inadequate cell number for TEM analysis. However, a lower dose of 1.5 mM induced 49% cell survival, and damaged 86% of the mitochondria, with 51% of the cells undergoing apoptosis. A dose of 1 mM chromic chloride produced 71% cell survival, and damaged 86% of the mitochondria, with 22% of the cells undergoing apoptosis. The amount of apoptosis correlated with overall cell survival by colony formation, but not with the amount of mitochondrial damage. The coordination of Cr(III) by picolinate ligands may alter the cellular chemistry of Cr(III) to make chromium picolinate a toxic form of Cr(III).

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