RESUMEN
The present investigation dealt with harmful effects of hexavalent chromium (Cr [VI]) on liver of Swiss albino mice. This variant exhibited cytotoxicity, mutagenicity, and carcinogenicity. Our study focused on elucidating the hepatotoxic effects of chronic low-dose exposure to Cr (VI) (2, 5, and 10 ppm) administered via drinking water for 4 and 8 months. The observed elevation in SGPT, ALP, and SGOT and increased oxidative stress markers unequivocally confirmed the severe disruption of liver homeostasis at these low treatment doses. Noteworthy alterations in histoarchitecture, body weight, and water intake provided further evidences of the harmful effects of Cr (VI). Production of reactive oxygen species (ROS) during metabolism led to DNA damages. Immunohistochemistry and qRT-PCR analyses revealed that chronic low-dose exposure of Cr (VI) induced apoptosis in liver tissue. Our study exhibited alterations in the expression pattern of DNA repair genes (Rad51, Mutyh, Mlh1, and Ogg1), coupled with promoter hypermethylation of Mutyh and Rad51, leading to transcriptional inhibition. Our findings underscored the potential of low-dose Cr (VI) exposure on hepatotoxicity by the intricate interplay between apoptosis induction and epigenetic alterations of DNA repair genes.
Asunto(s)
Apoptosis , Cromo , Metilación de ADN , Reparación del ADN , Hígado , Estrés Oxidativo , Regiones Promotoras Genéticas , Animales , Cromo/toxicidad , Estrés Oxidativo/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Regiones Promotoras Genéticas/efectos de los fármacos , Masculino , Especies Reactivas de Oxígeno/metabolismo , ADN Glicosilasas/genética , Relación Dosis-Respuesta a Droga , Daño del ADN/efectos de los fármacos , Recombinasa Rad51/genéticaRESUMEN
Arsenic (As) and chromium (Cr), two well-known cytotoxic and carcinogenic metals are reported to coexist in industrial effluents and groundwater. Their individual toxicities have been thoroughly studied but the combined effects, especially the mechanism of toxicity and cellular stress response remain unclear. Considering co-exposure as a more realistic scenario, current study compared the individual and mixture effects of As and Cr in the liver of zebrafish (Danio rerio). Fish were exposed to environmentally relevant concentrations of As and Cr for 15, 30 and 60 days. ROS generation, biochemical stress parameters like lipid peroxidation, reduced glutathione content, catalase activity and histological alterations were studied. Results showed increase in ROS production, MDA content and GSH level; and vicissitude in catalase activity as well as altered histoarchitecture, indicating oxidative stress conditions after individual and combined exposure of As and Cr which were additive in nature. This study also included the expression of Nrf2, the key regulator of antioxidant stress responses and its nuclear translocation. Related antioxidant and xenobiotic metabolizing enzyme genes like keap1, nqo1, ho1, mnsod and cyp1a were also studied. Overall results indicated increased nrf2, nqo1, ho1, mnsod expression at all time points and increased cyp1a expression after 60 days exposure. Emphasizing on the Nrf2-Keap1 pathway, this study exhibited additive or sometimes synergistic effects of As and Cr in zebrafish liver.
Asunto(s)
Arsénico , Enfermedad Hepática Inducida por Sustancias y Drogas , Animales , Pez Cebra/metabolismo , Arsénico/metabolismo , Antioxidantes/metabolismo , Cromo/toxicidad , Cromo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Catalasa/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés OxidativoRESUMEN
Chromium (Cr) is prevalently found in trivalent and hexavalent forms. Though the former is toxicologically benign due to its poor cellular permeability, hexavalent chromium i.e. Cr [VI] crosses the biological membrane and induces toxic effects in organisms. While Cr [VI] toxicity in humans is a subject of occupational exposure at industries involved in ferrochrome production, leather tanning, textile dyeing etc., aquatic abundance of Cr [VI] due to discharge of Cr-laden effluents by these industries lead to extensive toxicity in piscine species. The present review aims to discuss the mode of Cr [VI] entry in fish and the several inimical effects that it imparts on fish health. Such effects have been reported in various studies through behavioral, hormonal and hematological alterations. Bio-accumulation of Cr [VI] in vital organs and subsequent perturbation of the oxidative homeostasis leads to organotoxic effects like changes in organo-somatic indices and histo-architecture. At cellular level, Cr [VI] induced genotoxicity is often found to trigger cellular demise including apoptosis. This review also highlights the stress response in fish against Cr [VI] induced toxicity that is mediated through the expressional alteration of a myriad of anti-oxidant and xenobiotic-metabolizing proteins which is, in turn, a function of activated transcription programs including the Nrf2-ARE pathway.
Asunto(s)
Cromo , Ecotoxicología , Humanos , Animales , Cromo/toxicidad , Peces , AntioxidantesRESUMEN
Chromium VI (Cr (VI)) can cross cell membranes readily and causes the formation of Cr-DNA adducts, genomic damages, elevation of reactive oxygen species (ROS) and alteration of survival signaling pathways, as evidenced by the modulation in p53 signaling pathway. Mammals, including humans are exposed to Cr, including Cr (VI), frequently through inhalation, drinking water, and food. Several studies demonstrated that Cr (VI) induces cellular death through apoptosis and autophagy, genotoxicity, functional alteration of mitochondria, endocrine and reproductive impairments. In the present review, studies on deleterious effects of Cr (VI) exposure to mammalian cells (in vivo and in vitro) have been documented. Special attention is paid to the underlying molecular mechanism of Cr (VI) toxicity.