Korean J Physiol Pharmacol.  2021 Jul;25(4):321-331. 10.4196/kjpp.2021.25.4.321.

Protective effects of lutein against vancomycin-induced acute renal injury in mice via upregulation of peroxisome proliferatoractivated receptor gamma/nuclear factor erythroid 2-related factor 2 and inhibition nuclear factor-kappaB/caspase 3

• Emeka PM
• Rasool ST
• Morsy MA
• Hairul Islam MI
• Chohan MS

• KMID: 2516871
• DOI: http://doi.org/10.4196/kjpp.2021.25.4.321

Abstract

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

Keyword

Acute renal injury; Caspase-3; Lutein; PPAR gamma; Vancomycin

Figure

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  Fig. 1 Effect of lutein on (A) N-acetyl-β-D-glucosaminidase (NAG), (B) creatine kinase, (C) protein carbonyl, (D) malondialdehyde, and (E) caspase-3, in low (250 mg/kg) and high (500 mg/kg) dose vancomycin-induced renal injury in mice. Results are mean ± SD. L, lutein 200 mg/kg; VL, vancomycin 250 mg/kg; VH, vancomycin 500 mg/kg. *Shows significant different (p < 0.05) from control, while §indicates significant different (p < 0.05) from VL-treatment, and VH-treatment groups, respectively.

• 

  Fig. 2 Effect of lutein on histopathological changes in low (250 mg/kg) and high (500 mg/kg) dose vancomycin-induced renal injury in mice (A–F: H&E ×40). In (A, B) thick black arrow: normal glomerulus, thin black arrow: normal renal tubules. (C) Thick black arrow: abnormal dilatation of the renal tubules, thin black arrow: renal tubules filled with leukocytes, blue arrow: infiltration of inflammatory cells in the renal parenchyma. (D) Showing recovery of the parenchyma of the kidney (thick arrow and thin black arrows). (E) Thick black arrow: obliteration of renal tubules filled with necrotic cells, thin black arrow: necrosis of the epithelium of renal tubules. (F) Thick and thin black arrows: showing recovery of the parenchyma of kidney with no observed necrosis of epithial lining of renal tubules.

• 

  Fig. 3 Effect of lutein on (A) peroxisome proliferator-activated receptor gamma (PPARγ), (B) peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and (C), nuclear factor erythroid 2-related factor 2 (Nrf2) expressions respectively, in low (250 mg/kg) and high (500 mg/kg) dose vancomycin-induced renal injury in mice. Results are represented as mean ± SD. L, lutein; VL, 250 mg/kg vancomycin; VH, 500 mg/kg vancomycin; VL + L, 250 mg/kg + lutein; VH + L, 500 mg/kg + lutein. *Represent significant difference (p < 0.05) between control and vancomycin treated groups, while †represents significant difference (p < 0.05) between vancomycin treated and lutein plus vancomycin treatment groups. #Represents significant difference (p < 0.05) between control and lutein.

• 

  Fig. 4 Effect of lutein on nuclear factor-kappaB (NF-κB) expression in low (250 mg/kg) and high (500 mg/kg) dose vancomycin-induced renal injury in mice. Results are represented as mean ± SD. L, lutein; VL, 250 mg/kg vancomycin; VH, 500 mg/kg vancomycin; VL + L, 250 mg/kg + lutein; VH + L = 500 mg/kg + lutein. *Represent significant difference (p < 0.05) between control and vancomycin treated groups, while †represents significant difference (p < 0.05) between vancomycin treated and lutein plus vancomycin treatment groups.

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