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. 2021 Jul-Sep;104(3):368504211033703.
doi: 10.1177/00368504211033703.

Potassium bromate-induced nephrotoxicity and potential curative role of metformin loaded on gold nanoparticles

Ahmed S Abdel-Latif  1 , Sally E Abu-Risha  2 , Samaa M Bakr  3 , Wafaa M El-Kholy  1 , Mamdouh R El-Sawi  1
Affiliations

Potassium bromate-induced nephrotoxicity and potential curative role of metformin loaded on gold nanoparticles

Ahmed S Abdel-Latif et al. Sci Prog. 2021 Jul-Sep.

Abstract

Potassium bromate (KBrO3) is classified by the International Agency for Research on Cancer as a carcinogenic compound, where it causes renal tumors. The present study investigated the potential curative effect of metformin loaded on gold nanoparticles (MET AuNPs) in attenuating KBrO3-induced nephrotoxicity. Rats were divided into eight groups (control, MET, AuNPs, MET AuNPs, KBrO3, KBrO3/MET, KBrO3/AuNPS, and KBrO3/MET AuNPs). KBrO3 administration resulted in a significant elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), total bilirubin (TB), direct bilirubin (DB), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, urea, uric acid. Also, KBrO3 significantly increased renal malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) levels and reduced the activities of antioxidant molecules superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and Reduced glutathione (GSH). It also caused damaged DNA spots in comet assay and increased inflammatory IL-6 and apoptotic markers (caspase 3, Bax) while antiapoptotic Bcl-2 was significantly reduced. MET, AuNPS, MET AuNPS reduced the extent of renal damage induced by KBrO3 as indicated by decreased (AST, ALT, ALP, Alb, TP, TB, DB, creatinine, urea, uric, Lipid profile). MET, AuNPS, MET AuNPS showed a good curative effect against KBrO3-induced nephrotoxicity and MET AuNPS group showed better results compared with monotherapy.

Keywords: Metformin (MET); metformin loaded on gold nanoparticles (MET AuNPs); nephrotoxicity; potassium bromate (KBrO3).

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Lipid profiles of control and different treated rat groups.
Figure 2.
Figure 2.
Liver function tests of control and different treated rat groups.
Figure 3.
Figure 3.
Apoptotic markers in renal tissue of control and different treated rat groups.
Figure 4.
Figure 4.
Detection of DNA damage by comet assay in kidney cells: (a) control group rats with normal spots and round shape (untailed) (arrows) (comet assay; Scale bar = 100 lm), (b–d) MET group, AuNPs group, and MET/AuNPs group, respectively showing normal spots and round shape (comet assay; Scale bar = 100 lm), (e) KBrO3 group showing increase the number of damaged spots in which the length of the comet was greater than the diameter of the basal nuclear DNA (tailed) (arrowheads) (comet assay; Scale bar = 100 lm), and (f–h) KBrO3 group treated with MET, KBrO3 group treated with AuNPs, KBrO3 group treated with MET/AuNPs, respectively showing decreased the number of damaged spots (comet assay; Scale bar = 100 lm).
Figure 5.
Figure 5.
Photomicrograph of kidney from group normal control showing; normal renal corpuscles (white arrow), normal PCT and DCT with intact acidophilic brush border (T). H&E.
Figure 6.
Figure 6.
Photomicrograph of kidney from group MET showing slightly normal kidney tissue architecture with renal corpuscle (black arrow), with well identified PCT and DCT (T). H&E.
Figure 7.
Figure 7.
Photomicrograph of kidney from group AuNPs (a and b) showing; intact renal corpuscle with intact glomeruli (arrow) and intact renal tubules (T). H&E.
Figure 8.
Figure 8.
Photomicrograph of kidney from group MET + AuNPs showing: (a) renal cortex appeared with normal structure of renal corpuscle (arrow) and different types of renal tubules PCT and DCT (T) and (b) higher magnification of the previous showed normal renal corpuscle (arrow) and intact renal tubules (T). H&E.
Figure 9.
Figure 9.
Photomicrograph of kidney from group KBrO3 showing: (a) shrinkage glomeruli of renal corpuscle with widen capsular space (white arrow). Detached brush border with degeneration of some renal tubules (black arrow) and (b) the renal medulla showed severe degeneration of the epithelium lining of collecting tubules (arrow head). H&E.
Figure 10.
Figure 10.
Photomicrograph of kidney from group KBrO3 + MET showing: (a) histological structure of kidney with renal corpuscles (black arrow), kidney tubules (T) and (b) higher magnification to the previous figure showing mild degeneration in the glomerular tissue (black arrow) and mild degeneration in some tubular epithelium. H&E.
Figure 11.
Figure 11.
Photomicrograph of kidney from group KBrO3 + AuNPs showing: (a) renal cortex contains intact renal corpuscles (arrow) and renal tubules (T) and (b) higher magnification of renal cortex showing renal corpuscles (arrow) and mild pathological lesions in renal tubules (arrowhead). H&E.
Figure 12.
Figure 12.
Photomicrograph of kidney from group KBrO3 + MET AuNPs showing: (a) renal cortex with intact renal corpuscles (arrow) and different tubules PCT and DCT (T) and (b) higher magnification of the previous figure showing intact renal corpuscles (arrow) and tubular epithelium (T). H&E.
Figure 13.
Figure 13.
An electron micrograph of normal kidney showing proximal convoluted tubule with normal brush borders (white arrows) and normal mitochondria (black arrows).
Figure 14.
Figure 14.
An electron micrograph of normal kidney showing distilled convoluted tubule, blood vessel BV, and microvilli (white arrows).
Figure 15.
Figure 15.
An electron micrograph of normal kidney showing glomerulus tubule with normal basement membrane (white arrows).
Figure 16.
Figure 16.
An electron micrograph with high magnification of normal kidney showing portion contain filtration sites (black arrow) and basement membrane (white arrow).
Figure 17.
Figure 17.
An electron micrograph of kidney showing Proximal convoluted tubule with recovery brush borders (white arrows) and slightly vacuoles (black arrows) and lysosomes (LY).
Figure 18.
Figure 18.
An electron micrographs of recovery kidney showing distilled convoluted tubule with recover brush borders (white arrows).
Figure 19.
Figure 19.
An electron micrograph of recovery kidney showing glomerulus tubule with recovery basement membrane which is slightly irregular and thick (white arrows).
Figure 20.
Figure 20.
An electron micrograph of kidney showing proximal convoluted tubule which lost brush borders (white arrows) with much vacuoles (black arrows) and many lysosomes (LY).
Figure 21.
Figure 21.
An electron micrograph of kidney showing plasma cell (inflammatory cell) (white arrows).
Figure 22.
Figure 22.
An electron micrograph of kidney showing glomerulus tubule with irregular basement membrane with a large thickening and fusion in pedicel (white arrows).
Figure 23.
Figure 23.
Gold nanoparticles (AuNPs) were examined by UV/VIS spectrophotometer particles’ absorbance was maintained at a range between 200 and 800 nm.
Figure 24.
Figure 24.
Electron micrograph of AuNPs suspension on transmission electron microscopy (TEM) showing a majority of almost spheroidal to rod shaped gold nanoparticles with diameters ranging between 15.8 and 19.6 nm.
Figure 25.
Figure 25.
Physical appearance of AuNPs.
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