Prethodna terapija vitaminom C štiti od niklom izazvane nefrotoksičnosti u miševa

Nickel is an abundant carcinogenic and nephrotoxic metal whose activity leads to renal impairment. Previous studies have shown a protective effect of simultaneous vitamin C administration on acute and chronic nickel toxicity. However, very little research relating to the effect of vitamin C pretreatment in preventing nickel-induced acute nephrotoxicity is available. Therefore, the present study aimed to determine the efficiency of vitamin C (VC) pretreatment in preventing acute renal toxicity of nickel. Mice were pretreated orally with vitamin C (16.6 mg kg-1 body weight, b.w.) for seven consecutive days, prior to intraperitoneal (i.p.) administration of nickel chloride at different doses (3, 5, and 10 mg Ni kg-1 b.w.) for an exposure period of 24 hours. Thereafter, animals were killed and kidney tissue and blood samples were taken for histological examination and biochemical marker analyses. Vitamin C pretreatment alone did not alter the levels of serum kidney markers (creatinine, urea, and uric acid). However, treatment with Ni alone showed a significant increase in the levels of serum creatinine, urea, and uric acid with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney sections as compared to the control group. Pretreatment with vitamin C and treatment with Ni at all doses tested for 24 hours showed a significant decrease in the levels of serum creatinine, urea, and uric acid, as well as an improvement in histological changes compared to those previously seen in the group treated with Ni alone. It is concluded that vitamin C pretreatment effectively improved renal function and tissue damage caused by nickel.Nikal je sveprisutan kancerogeni i nefrotoksični metal čije djelovanje dovodi do oštećenja bubrežne funkcije. Rezultati prethodnih istraživanja dokazali su zaštitni učinak istodobne terapije vitaminom C na akutnu i kroničnu toksičnost izazvanu niklom. Međutim, vrlo je malo istraživanja o učinku prethodne terapije vitaminom C radi sprječavanja niklom izazvane akutne nefrotoksičnosti. Stoga se ovim ispitivanjem nastojala utvrditi učinkovitost prethodne terapije vitaminom C (VC) u sprječavanju akutne bubrežne toksičnosti izazvane niklom. Prije intraperitonealnog (IP) ubrizgavanja različitih doza (3, 5 i 10 mg Ni kg-1 tjelesne težine) nikal klorida u razdoblju izlaganja od 24 sata, miševi su sedam dana uzastopce dobivali oralnu terapiju vitaminom C (16,6 mg kg-1 tjelesne težine). Nakon toga životinje su usmrćene, a bubrežno tkivo i uzorci krvi uzeti su radi histološke obrade i analize biokemijskih markera. U miševa koji su dobivali samo terapiju vitaminom C, serumske razine bubrežnih markera (kreatinin, urea i mokraćna kiselina) nisu bile promijenjene. Međutim, tretiranje samo niklom dovelo je do značajnog povećanja razina kreatinina, ureje i mokraćne kiseline te do značajnog broja nekrotičnih epitelnih stanica i infiltracije upalnih stanica u presjecima bubrega u usporedbi s kontrolnom skupinom. Prethodna terapija vitaminom C i tretiranje niklom u svim navedenim dozama tijekom 24 sata doveli su do značajnog smanjenja razina kreatinina, ureje i mokraćne kiseline u serumu te do poboljšanja histoloških promjena u usporedbi sa skupinom koja je tretirana samo niklom. Zaključuje se da prethodna terapija vitaminom C učinkovito poboljšava bubrežnu funkciju i oštećenje tkiva uzrokovano niklom

EFFECT OF THE JOINT SUPPLEMENTATION OF VITAMIN C AND VITAMIN E ON NICKEL HEAMATOTOXICITY AND NEPHROTOXICITY IN MALE SWISS ALBINO MICE

Objective: The aim of this study was to investigate the effect of vitamins C and E separately and in combination against nickel-induced alterations in haematological indices and kidney dysfunction. Methods: Male Swiss albino mice were divided into eight equal groups: Control, vitamin C (Vit C), vitamin E (Vit E), vitamin C and vitamin E (Vit C+Vit E), nickel (Ni), nickel and vitamin C (Ni+Vit C), nickel and vitamin E (Ni+Vit E), and nickel plus vitamins C and E (Ni+Vit C+Vit E). Vitamin C (1g/l) was given to mice through their drinking water. Vitamin E (1g/kg) and nickel as nickel sulfate (2.7 mg/kg) were supplemented in diet for four weeks.Results: Nickel caused a significant decrease in body weight, food and water consumption along with significant increase in the absolute and relative kidney weights. Haemoglobin, red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt) and packed cell volume (PCV) were significantly diminished, while white blood cells count (WBC) increased in nickel exposed mice. The renal damage induced by nickel was evidenced by a significant increase in the levels of serum urea, creatinine and uric acid. However, vitamins C and E in combination more significantly ameliorated the altered histopathological and biochemical changes in the kidney as well as hematological parameters of Ni intoxicated mice than either vitamin C or E.Conclusion: The study showed that vitamin C and E combination effectively attenuated Ni-induced heamatotoxicity and nephrotoxiicty in mice.Keywords: Nickel, Vitamins C, Vitamin E, Heamatotoxicity, Kidney injury, Histopatholog

Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line

Lee W-K, Probst S, Scharner B, Deba T, Dahdouh F, Thévenod F. Distinct concentration-dependent oxidative stress profiles by cadmium in a rat kidney proximal tubule cell line. Archives of Toxicology . 2024;98(4):1043–1059.Levels and chemical species of reactive oxygen/nitrogen species (ROS/RNS) determine oxidative eustress and distress. Abundance of uptake pathways and high oxygen consumption for ATP-dependent transport makes the renal proximal tubule particularly susceptible to cadmium (Cd2+)-induced oxidative stress by targeting ROS/RNS generation or antioxidant defence mechanisms, such as superoxide dismutase (SOD) or H2O2-metabolizing catalase (CAT). Though ROS/RNS are well-evidenced, the role of distinct ROS profiles in Cd2+ concentration-dependent toxicity is not clear. In renal cells, Cd2+ (10-50 M) oxidized dihydrorhodamine 123, reaching a maximum at 2-3 h. Increases (up to fourfold) in lipid peroxidation by TBARS assay and H2O2 by Amplex Red were evident within 30 min. ROS and loss in cell viability by MTT assay with 50 M Cd2+ could not be fully reversed by SOD mimetics Tempol and MnTBAP nor by SOD1 overexpression, whereas CAT expression and alpha-tocopherol were effective. SOD and CAT activities were attenuated below controls only with >6 h 50 M Cd2+, yet augmented by up to 1.5- and 1.2-fold, respectively, by 10 M Cd2+. Moreover, 10 M, but not 25-50 M Cd2+, caused 1.7-fold increase in superoxide anion (O2-), detected by dihydroethidium, paralled byloss in cell viability, that was abolished by Tempol, MnTBAP, alpha-tocopherol and SOD1 or CAT overexpression. H2O2-generating NADPH oxidase 4 (NOX4) was attenuated by ~50% with 10M Cd2+ at 3h compared to upregulation by 50 M Cd2+ (~1.4-fold, 30 min), which was sustained for 24h. In summary, O2- predominates with low-moderate Cd2+, driving an adaptive response, whereas oxidative stress by elevated H2O2 at high Cd2+ triggers cell death signaling pathways.Highlights Different levels of reactive oxygen species are generated, depending on cadmium concentration. Superoxide anion predominates and H2O2 is suppressed with low cadmium representing oxidative eustress. High cadmium fosters H2O2 by inhibiting catalase and increasing NOX4 leading to oxidative distress. Superoxide dismutase mimetics and overexpression were less effective with high versus low cadmium. Oxidative stress profile could dictate downstream signalling pathways. © 2024. The Author(s)