+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria



Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria



Biochemical Pharmacology 45(10): 2017-2024



Studies were undertaken to investigate the principal actions underlying mercury-induced oxidative stress in the kidney. Mitochondria from kidneys of rats treated with HgCl2 (1.5 mg/kg i.p.) demonstrated a 2-fold increase in hydrogen peroxide (H2O2) formation for up to 6 hr following Hg(II) treatment using succinate as the electron transport chain substrate. No increase in H2O2 formation was observed when NAD-linked substrates (malate/glutamate) were used, suggesting that Hg(II) affects H2O2 formation principally at the ubiquinone-cytochrome b region of the mitochondrial respiratory chain in vivo. Together with increased H2O2 formation, mitochondrial glutathione (GSH) content was depleted by more than 50% following Hg(II) treatment, whereas formation of thiobarbiturate reactive substances (TBARS), indicative of mitochondrial lipid peroxidation, was increased by 68%. Studies in vivo revealed a significant concentration-related depolarization of the inner mitochondrial membrane following the addition of Hg(II) to mitochondria isolated from kidneys of untreated rats. This effect was accompanied by significantly increased H2O2 formation, GSH depletion and TBARS formation linked to both NADH dehydrogenase (rotenone-inhibited) and ubiquinone-cytochrome b (antimycin-inhibited) regions of the electron transport chain. Oxidation of pyridine nucleotides (NAD[P]H) was also observed in mitochondria incubated with Hg(II) in vitro. In further studies in vitro, the potential role of Ca2+ in Hg(II)-induced mitochondrial oxidative stress was investigated. Ca2+ alone (30-400 nmol/mg protein) produced no increase in H2O2 and only a slight increase in TBARS formation when incubated with kidney mitochondria isolated from untreated rats. However, Ca2+ significantly increased H2O2 and TBARS formation elicited by Hg(II) at the ubiquinone-cytochrome b region of the mitochondrial electron transport chain, whereas TBARS formation was decreased significantly when the Ca2+ uptake inhibitors, ruthenium red or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA), were included with Hg(II) in the reaction mixtures. These findings support the view that Hg(II) causes depolarization of the mitochondrial inner membrane with consequent increased H2O2 formation. These events, coupled with Hg(II)-mediated GSH depletion and pyridine nucleotide oxidation, create an oxidant stress condition characterized by increased susceptibility of mitochondrial membranes to iron-dependent lipid peroxidation (TBARS formation). Since increased H2O2 formation, GSH depletion and lipid peroxidation were also observed in vivo following Hg(II) treatment, these events may underlie oxidative tissue damage caused by mercury compounds. Moreover, Hg(II)-induced alterations in mitochondrial Ca2+ homeostasis may exacerbate Hg(II)-induced oxidative stress in kidney cells.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 047461655

Download citation: RISBibTeXText

PMID: 8512585

DOI: 10.1016/0006-2952(93)90012-l


Related references

In vivo administration of D609 leads to protection of subsequently isolated gerbil brain mitochondria subjected to in vitro oxidative stress induced by amyloid beta-peptide and other oxidative stressors: relevance to Alzheimer's disease and other oxidative stress-related neurodegenerative disorders. Free Radical Biology and Medicine 41(11): 1694-1703, 2006

In vitro and in vivo studies of Allium sativum extract against deltamethrin-induced oxidative stress in rats brain and kidney. Archives of Physiology and Biochemistry 124(3): 207-217, 2018

Ursodeoxycholic acid prevents selenite-induced oxidative stress and alleviates cataract formation: In vitro and in vivo studies. Molecular Vision 18: 151-160, 2012

Effect of Centella asiatica leaf powder on oxidative markers in brain regions of prepubertal mice in vivo and its in vitro efficacy to ameliorate 3-NPA-induced oxidative stress in mitochondria. Phytomedicine 15(11): 971-984, 2008

Free Radical Scavenging Properties of Skin and Pulp Extracts of Different Grape Cultivars In Vitro and Attenuation of H2O2-Induced Oxidative Stress in Liver Tissue Ex Vivo. Indian Journal of Clinical Biochemistry 30(3): 305-312, 2015

Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. Biochemical Pharmacology 42 Suppl: S181-S187, 1991

Propofol attenuates H 2 O 2 -induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes. Apoptosis 22(5): 639-646, 2017

Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways. Molecular Medicine Reports 17(5): 7258-7264, 2018

In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in piebaldism. Experimental Dermatology 19(10): 883-887, 2010

Effect of experimental and cold exposure induced hyperthyroidism on H2O2 production and susceptibility to oxidative stress of rat liver mitochondria. Archives of Biochemistry and Biophysics 447(1): 11-22, 2006

Protective effect of whey protein hydrolysates on H₂O₂-induced PC12 cells oxidative stress via a mitochondria-mediated pathway. Food Chemistry 141(2): 847-852, 2013

Anti-oxidative and anti-apoptosis effects of egg white peptide, Trp-Asn-Trp-Ala-Asp, against H2O2-induced oxidative stress in human embryonic kidney 293 cells. Food and Function 5(12): 3179-3188, 2014

A novel porcine ex vivo retina culture model for oxidative stress induced by H₂O₂. Alternatives to Laboratory Animals 45(1): 11-25, 2017

Protein carbonyl formation following in vivo intracerebral hemorrhage and in vitro iron-induced oxidative stress. Journal of Neurochemistry 72(Suppl. ): S33, 1999

Cytoprotective effect of white tea against H2O2-induced oxidative stress in vitro. Food Chemistry 141(4): 4107-4114, 2013