Metal Carcinogenesis and DNA Damage: A Case Study Using Hexavalent Chromium

The current study focused on investigating the renoprotective effects of grape seed oil (GSO) against hexavalent chromium (Cr (VI))-induced nephrotoxicity. A total of 40 male rats were randomly divided into four groups: group I served as the control group, group II received 1000 mg/L potassium dichromate (353.5 mg/L Cr(VI)) in drinking water for 12 weeks, group III received 3.7 g/kg body weight/day GSO orally for 12 weeks, and group IV received GSO together with potassium dichromate for 12 weeks. Cr(VI) significantly increased serum levels of urea, creatinine, potassium and glucose. In addition, Cr(VI) increased MDA levels and induced renal tissue damage and DNA damage. On the other hand, Cr(VI) decreased serum levels of sodium and antioxidant defence system [reduced glutathione (GSH) and catalase (CAT)]. However, treatment with GSO prevented elevation levels of serum urea, creatinine, potassium and glucose. In addition, GSO enhanced sodium level, renal tissue antioxidant defense system due to its curative effect ameliorated particularly oxidative stress, renal tissue and DNA damage. In conclusion, these results demonstrate that GSO is a promising nephroprotective agent against Cr(VI)-induced nephrotoxicity.Key words: grape seed oil; hexavalent chromium; nephrotoxicity; DNA damage BLAŽILNI UČINKI OLJA GROZDNIH PEŠK PRI TOKSIČNI OBREMENITVI LEDVIC TER VPLIV NA OKSIDATIVNI STRES PODGAN, POVZROČEN S KROMOM Povzetek: Študija je bila osredotočena na proučevanje zaščitnih učinkov olja grozdnih pešk (GSO) pri toksični obremenitvi ledvic, povzročeni s heksavalentnim kromom (Cr (VI)). Štirideset samcev podgan je bilo naključno razdeljenih v štiri skupine: skupina I - kontrolna skupina, skupina II, ki je v pitni vodi 12 tednov prejemala 1000 mg/L kalijevega dikromata (353,5 mg/L Cr (VI)), skupina III, ki je peroralno 12 tednov prejemala 3,7 g/kg telesne mase/dan GSO ter skupina IV, ki je 12 tednov prejemala GSO skupaj s kalijevim dikromatom. Cr(VI) je znatno zvišal serumske ravni sečnine, kreatinina, kalija in glukoze v serumu. Poleg tega je Cr(VI) zvišal raven MDA in povzročil poškodbe ledvičnega tkiva in poškodbe DNK. Po drugi strani je Cr(VI) znižal serumsko raven natrija in antioksidativnega obrambnega sistema, zmanjšal raven glutationske peroksidaze in katalaze. Dodajanje GSO poskusnim živalim je preprečilo zvišanje ravni sečnine v serumu, kreatinina, kalija, natrija in glukoze. Poleg tega je GSO izboljšal obrambni sistem antioksidantov ledvičnega tkiva. Zaradi svojega zdravilnega učinka je izboljšal zlasti oksidativni stres, poškodbe ledvičnega tkiva in DNK. Rezultati kažejo, da je GSO obetavno zaščitno sredstvo za ledvica pri toksični obremenitvi, povzročeni s Cr(VI).Ključne besede: olje grozdnih pešk; heksavalentni krom; nefrotoksičnost; poškodba DNK

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Role of Bacillus subtilis Error Prevention Oxidized Guanine System in Counteracting Hexavalent Chromium-Promoted Oxidative DNA Damage

Applied and Environmental Microbiology ◽

10.1128/aem.01665-14 ◽

2014 ◽

Vol 80 (17) ◽

pp. 5493-5502 ◽

Cited By ~ 6

Author(s):

Fernando Santos-Escobar ◽

J. Félix Gutiérrez-Corona ◽

Mario Pedraza-Reyes

Keyword(s):

Dna Damage ◽

Bacillus Subtilis ◽

Hexavalent Chromium ◽

Oxidative Dna Damage ◽

Chromosomal Dna ◽

Error Prevention ◽

Content Type ◽

Induced Mutagenesis ◽

Oxidized Guanine ◽

Life On Earth

ABSTRACTChromium pollution is potentially detrimental to bacterial soil communities, compromising carbon and nitrogen cycles that are essential for life on earth. It has been proposed that intracellular reduction of hexavalent chromium [Cr(VI)] to trivalent chromium [Cr(III)] may cause bacterial death by a mechanism that involves reactive oxygen species (ROS)-induced DNA damage; the molecular basis of the phenomenon was investigated in this work. Here, we report thatBacillus subtiliscells lacking a functional error prevention oxidized guanine (GO) system were significantly more sensitive to Cr(VI) treatment than cells of the wild-type (WT) strain, suggesting that oxidative damage to DNA is involved in the deleterious effects of the oxyanion. In agreement with this suggestion, Cr(VI) dramatically increased the ROS concentration and induced mutagenesis in a GO-deficientB. subtilisstrain. Alkaline gel electrophoresis (AGE) analysis of chromosomal DNA of WT and ΔGO mutant strains subjected to Cr(VI) treatment revealed that the DNA of the ΔGO strain was more susceptible to DNA glycosylase Fpg attack, suggesting that chromium genotoxicity is associated with 7,8-dihydro-8-oxodeoxyguanosine (8-oxo-G) lesions. In support of this notion, specific monoclonal antibodies detected the accumulation of 8-oxo-G lesions in the chromosomes ofB. subtiliscells subjected to Cr(VI) treatment. We conclude that Cr(VI) promotes mutagenesis and cell death inB. subtilisby a mechanism that involves radical oxygen attack of DNA, generating 8-oxo-G, and that such effects are counteracted by the prevention and repair GO system.

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