Table 2.

Summary of chemoprevention for Cr(III) and Cr(VI) carcinogenicity

Category	Cr(III)	Cr(VI)
In vivo studies	• Few chemoprevention investigations  ○ Selenium in C3H mice with MMTV: Cr(III) weakens antitumorigenic effects of Se, counteracts inhibitory effect on tumor development, shortens tumor latency period, and accelerates tumor-growth rates107	• Antioxidants with chemopreventive effects against Cr(VI) cyto/genotoxicity:  ○ EDE in Swiss mice: prevents pathological liver and kidney damage71  ○ NAC in albino Hartley strain GPs: inhibits activation of phospho-Akt, phospho-p65, phospho-IκBα, phospho-ERK, phospho-p38, and phospho-JNK in epidermis74  ○ GSH in Swiss albino mice and Wistar rats: protects against LP, oxidative stress, and DNA damage, restores GSH cycle in liver and kidney4,91  ○ EGCG in Hsd:ICR and CD1 mice: protects against genotoxic damage, contributes to elimination of DNA-damaged cells92,93  ○ Quercetin in nude mice with BEAS-2B and CD1 mice: reduces tumor incidence, targets miR21–PDCD4 signaling, protects against genotoxic damage46,93  ○ Rutin in CD1 mice: protects against genotoxic damage93  ○ Curcumin in Wistar rats: direct and indirect antioxidant effects against renal oxidant damage, preserves mitochondrial function95  ○ Selenium in Wistar rats: prevents against Cr(VI)-induced erythrocyte damage, inhibits LP and oxidative stress, restores GSH cycle in liver and kidney4,97,98  ○ α-tocopherol in Wistar rats: inhibits LP and oxidative stress, restores GSH cycle in liver and kidney4  ○ Ginger in Wistar rats: reduces intensity of oxidative stress98  ○ Vitamins C and E in albino rats and Swiss mice: reduce oxidative damage and decrease LP and sperm mutations and germ cells degenerated99  ○ Propylthiouracil in mice: reduces oxidative stress and protects against hepatotoxicity101  ○ Green-tea polyphenol extracts in CD1 mice: reduces amount of MN-PCEs102,103 Thiol compounds (including LA and DHLA) in ddY and Swiss albino mice: reduce oxidative stress and generation of DPCs, scavenge ROS, alter cell-redox status, boost urinary chromium excretion104,105
In vitro studies	• Few chemoprevention studies conducted • Antioxidants with chemopreventive effects against Cr(III) cyto/genotoxicity:  ○ Tempol in human lymphocytes: inhibits cyto/genotoxicity82  ○ Zinc in PBL: inhibits apoptosis, reduces ROS production, reverses changes in mitochondrial membrane potential, ATP levels, activation of caspase 390	• Antioxidants with chemopreventive effects against Cr(VI) cyto/genotoxicity:  ○ Apple juice in A549: scavenges hydroxyl radicals, reduces lipid peroxidation, DNA damage, cell apoptosis, NFκB activation68  ○ Quercetin in BEAS2B: decreases ROS generation, inhibits cell transformation, increases miR21 expression, and inhibits of PDCD469  ○ Luteolin in BEAS2B: scavenges ROS46  ○ EDE in AMJ2-C11: protects against cytotoxicity and oxidative stress71  ○ Tempol in human lymphocytes: inhibits cyto- and genotoxicity82  ○ NAC in L02 hepatocytes, H460, HaCaT: inhibits suppression of apoptosis, p53 activation, HSP72 and HIF1α upregulation, prevents ROS-mediated cell death and cytokine expression, decreases rate of cell apoptosis, alleviates mitochondrial and DNA damage73–75  ○ Vitamin C: inhibits increase in DPCs, complete protection against cytotoxicity76  ○ Lawsonia inermis extract in MDA-MB-435S: scavenges free radicals, inhibits lipid peroxidation80  ○ Phyllanthus amarus aqueous extract in MDA-MB-435S: inhibits Cr(VI)-induced oxidative toxicity81  ○ EGCG in BEAS2B: scavenges ROS, protects against DNA damage, inhibits activation of NFκB7  ○ Melatonin in rat hepatocytes: protects against DSBs, cytotoxicity, lipid peroxidation88  ○ MCE in BEAS2B, PBL: increases cell viability, decreases DNA damage and ROS level89

Abbreviations: Cr(VI), hexavalent chromium; Cr(III), trivalent chromium; EDE, Eugenia dysenterica extract (leaf, hydroalcoholic); NAC, N-acetylcysteine; MMTV, murine mammary tumor virus; GPs, guinea pigs; GSH, glutathione; EGCG, epigallocatechin-3-gallate; MN-PCEs, micronucleated polychromatic erythrocytes; LP, lipid peroxidation; LA, α-lipoic acid; DHLA, dihydrolipoic acid; ROS, reactive oxygen species; PBL, peripheral blood lymphocyte; DPCs, DNA–protein cross-links; DSBs, double-strand breaks; MCE, methanolic Carum copticum extract (seeds).