Tag Archives: nephrotoxicity

Effect of selenium and nano-selenium on cisplatin-induced nephrotoxicity in albino rats

M. M. A. Shafaee1, H. S. Mohamed2, S. A. Ahmed1, M. A. Kandeil3

1Chemistry department, Faculty of Science, Beni-Suef University, Egypt;
2Research Institute of Medicinal and Aromatic Plants, Beni-Suef University, Egypt;
3Biochemistry department, Faculty of Veterinary medicine, Beni-Suef University, Egypt;
e-mail: husseinshaban@science.bsu.edu.eg

Received: 05 July 2019; Accepted: 18 October 2019

Cisplatin is commonly used as a chemotherapeutic agent useful in the treatment of several forms of cancer, but its use is limited due to the undesirable side effects of nephrotoxicity. Most of the previous researches found a positive effect of using selenium as an antioxidant on the toxicity of cisplatin during short term administrations  although the recommended dose regimen of cisplatin in chemotherapy is multiple successive administration every three or four weeks depending on the type of the tumor. The aim of this study was to examine the effects of long term usage of selenium or nano-selenium on cisplatin-induced nephrotoxicity in albino rats. Forty rats were divided into equal four groups, 1st group as a control injected with normal saline, 2nd group injected with cisplatin 6 mg/kg every 21 days for 70 days (experimental period), 3rd group injected with cisplatin 6 mg/kg plus intramuscular injection 0.1 mg/kg selenium in the form of sodium selenite every 3 days during the experimental period, the 4th group injected with cisplatin 6 mg/kg plus intramuscular injection 0.1 mg/kg nano-selenium every 3 days during the experimental period. The results indicated that selenium or nano-selenium exerted an antioxidant effect through increasing the level of antioxidant enzymes in both serum and kidney tissue, while, it shows a negative effect on kidney function through increasing serum urea and creatinine concentrations and causing abnormal morphology of kidney tissue for rats treated with cisplatin during experimental period.

Changes of the state of rat kidneys under Guerin carcinoma development and use of cytostatics

S. A. Babiy1, T. F. Loskutova2, N. I. Shtemenko1

1Oles Gonchar Dnipropetrovsk National University, Ukraine;
2Dnipropetrovsk State Medical Acadamy, Ukraine;
e-mail: babiy_s@meta.ua

It was shown that development of the Guerin carcinoma and introduction of cisplatin led to the damage of the kidneys of rats that was confirmed by a relative increase of weight, proteinuria, change of γ-glutamyl transpeptidase and lactate dehydrogenase activity in the urea and tissue homogenates of the kidneys, by a decrease of relative reabsorption and glomerular filtration. Introduction of nanoliposomal forms of the rhenium cluster compounds led to normalization of above mentioned diagnostic indexes and to reduction of the toxic cisplatin influence that was confirmed by biochemical and morphological investigations.

Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

L. I. Kоbylinska1, D. Ya. Havrylyuk1, N. E. Mitina2, A. S. Zаichenko2,
R. B. Lesyk1, B. S. Zіmenkovsky1, R. S. Stoika3

 1Danylo Halytsky Lviv National Medical University, Ukraine;
e-mail: stoika@cellbiol.lviv.ua;
2Lviv Polytechnic National University, Ukraine;
3Іnstitute of Cell Biology, National Academy of Sciences of Ukraine, Lviv

The aim of this study was to compare the effect of new synthetic 4-thiazolidinone derivatives (potential anticancer compounds denoted as 3882, 3288 and 3833) and doxorubicin (positive control) in free form and in their complexes with synthetic polyethylene glycol-containing nanoscale polymeric carrier on the biochemical indicators of nephrotoxicity in blood serum of rats. The concentration of total protein, urea, creatinine, glucose, ions of sodium, potassium, calcium, iron and chloride was measured. It was found that after injection of the investigated compounds, the concentration of sodium cations and chloride anions in blood serum was increased compared with control (untreated animals). Doxorubicin’s injection was accompanied by a decrease in the concentration of iron cations. The concentration of total protein, urea and creatinine decreased under the influence of the studied compounds. Complexation of these аntineoplastic substances with a synthetic polymeric nanocarrier lowered the concentration of the investigated metabolites substantially compared to the effect of these compounds in free form. The normalization of concentration of total protein, urea and creatinine in blood serum of rats treated with complexes of the studied compounds with the polymeric carrier comparing with increased concentration of these indicators at the introduction of such compounds in free form was found.

Antitoxic and antioxidant effects of N-stearoylethanolamin in the content of nanocomposite complex with doxorubicin in organs of mice with Lewis carcinoma

E. A. Gudz1, N. M. Hula1, T. N. Goridko1, Y. M. Bashta1,
A. I. Voyeikov1, A. G. Berdyshev1, H. V. Kosiakova2,
R. R. Panchuk3, R. S. Stoika2, A. A. Ryabtseva3, O. S. Zaichenko3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua;
2Institute Biology of Cell, National Academy of Sciences of Ukraine, Lviv;
3National University “Lvov Politekhnika”, Ukraine

The aim of the study was to evaluate the possibility to reduce the doxorubicin toxic effects by its immobilization with N-stearoylethanolamine (NSE) on nanocarier polyethylene glycol. The studied  parameters of the doxorubicin toxicity were: the level of creatinine in the mice blood plasma and activity of alanine aminotransferase and aspartate aminotransferase in the blood plasma of mice. The activity of catalase superoxide dismutase, glutathione peroxidase and intensity of lipid peroxidation was determined in the tissues of the heart, kidneys and liver. Doxorubicin in the content of nanocarrier alone caused an increase of serum creatinine and aspartateaminotrasferase activity in plasma of experimental animals with carcinoma. Nanocomposite which contained doxorubicin and NSE, did not cause an increase of these parameters. It has been shown that the administration of a carrier containing doxorubicin to mice with Lewis lung carcinoma caused the decrease of  catalase  activity in mice with carcinoma. The combination of NSE and doxorubicin on the carrier led to the normalization of this parameter to the level of intact animals. NSE immobilized on a carrier together with doxorubicin caused a decrease in the activity of superoxide dismutase in the kidney tissue of mice with tumor. The tumor growth caused the increase of the of superoxide dismutase in mice. The administration of a carrier which contained doxorubicin and NSE normalized superoxide dismutase in heart tissue contrary of kidney. The obtained results show the antitoxic and antioxidant effects of N-stearoylethanolamine immobilized in the nanocarrier complex together with doxorubicin.

Organ-specific antitoxic effects of N-stearoilethanolamine male mice with lewis carcinoma under indoxorubicin intoxication

E. A. Goudz, N. M. Gulа, T. N. Goridko, Y. N. Bashta, A. I. Voyeikov

Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: ngula@biochem.kiev.ua

With the introduction of doxorubicin into mice with Lewis carcinoma in the heart and liver tissues and kidney the organ-antitoxic effects of N-stearoilethanolamine (NSE) were found, which depended on its concentration. Administration of doxorubicin to male mice leads to an increase in the level of urea and creatinine, as well as activation of ALT in blood plasma. Introduction of NSE resulted in normalization of these parameters to the level of intact animals. In the heart tissue  doxorubicin has multi-directional effects on the activity of antioxidant enzymes, in particular it decreases the activity of catalase and superoxide dismutase activity increases. Introduction of NSE normalizes these two indicators. It was found that tumor growth leads to an increase in the activity of glutathione peroxidase and superoxide dismutase. Introduction of NSE normalizes activity of these enzymes. Doxorubicin causes an increase in catalase activity in the kidney of mice with tumour, NSE prevented the increase in the activity of the above enzyme. The cancer process leads to increased levels of catalase activity in the liver of tumour-bearing mice, the introduction of NSE decreases the enzyme activity.