Antioxidant, Antiinflammatory and Antiapoptotic Effects of Lycopene in Rats With Vancomycin-Induced Nephrotoxicity

Abstract

Background: The most important side effect of vancomycin (Vanco) is nephrotoxicity (NPT). Lycopene (Lyco) has been reported to have anti-inflammatory and anti-apoptotic properties in addition to its antioxidant activity. The aim is to investigate the protective efficacy of Lyco against the NPT condition that limits the use of Vanco.

Method: A total of 48 rats were used in the study in six groups of eight rats each, namely, Corn Oil Control, Lyco 5, Lyco 10, Vanco, Vanco + Lyco 5 and Vanco + Lyco 10.

Results: Vanco (400 mg/kg, intraperitoneal) administered for 7 days elevated serum BUN, creatinine, uric acid levels and renal lipid peroxidation while decreasing renal GSH and the activity of the antioxidant enzymes SOD, CAT and GPx. Vanco also increased the levels of inflammatory markers NF-κB, TNF-α, Bcl-3 and p38α MAPK activity. It decreased the level of AQP-1 and increased the level of NGAL. In addition, it activated apoptosis by decreasing Bcl-2 and Procas-3 expression levels while increasing apoptotic p53, Bax and Cyt-c expression levels. Lyco treatment at both doses (5 and 10 mg/kg, orally) ameliorated NPT by reducing oxidative stress, inflammation and apoptosis, while the higher dose was more effective.

Conclusion: The findings showed that Lyco attenuated Vanco-induced NPT.

Keywords: apoptosis; inflammation; lycopene; nephrotoxicity; oxidative stress; vancomycin.

FIGURE 1

Effects of vancomycin (Vanco) and lycopene (Lyco) administrations on (A) blood urea nitrogen (BUN), (B) creatinine (CRE) and (C) uric acid (UA) levels in serum of rats. Values are given as mean ± SD CO Control versus others: *p < 0.05, **p < 0.01, ***p < 0.001; Vanco versus others: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001; Vanco + Lyco 5 versus Vanco + Lyco 10: ^& p < 0.05, ^&& p < 0.01, ^&&& p < 0.001.

FIGURE 2

Effects of vancomycin (Vanco) and lycopene (Lyco) administrations on (A) malondialdehyde (MDA), (B) reduced glutathione (GSH), (C) superoxide dismutase (SOD), (D) catalase (CAT), (E) glutathione peroxidase (GPx) and (F) NADPH oxidase 4 (NOX‐4) levels in kidney tissues of rats. Values are given as mean ± SD CO Control versus others: *p < 0.05, **p < 0.01, ***p < 0.001; Vanco versus others: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001; Vanco + Lyco 5 versus Vanco + Lyco 10: ^& p < 0.05, ^&& p < 0.01, ^&&& p < 0.001.

FIGURE 3

Effects of vancomycin (Vanco) and lycopene (Lyco) administrations on (A) nuclear factor kappa B (NF‐κB), (B) tumour necrosis factor‐alpha (TNF‐α), (C) B‐cell lymphoma 3 (Bcl‐3) and (D) mitogen‐activated protein kinase p38 alpha (p38α MAPK) levels in kidney tissues of rats. Values are given as mean ± SD CO Control versus others: *p < 0.05, **p < 0.01, ***p < 0.001; Vanco versus others: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001; Vanco + Lyco 5 versus Vanco + Lyco 10: ^& p < 0.05, ^&& p < 0.01, ^&&& p < 0.001.

FIGURE 4

Effects of vancomycin (Vanco) and lycopene (Lyco) administrations on (A) tumour protein 53 (p53), (B) aquaporin 1 (AQP‐1) and (C) neutrophil gelatinase‐associated lipocalin (NGAL) levels in kidney tissues of rats. Values are given as mean ± SD CO Control versus others: *p < 0.05, **p < 0.01, ***p < 0.001; Vanco versus others: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001; Vanco + Lyco 5 versus Vanco + Lyco 10: ^& p < 0.05, ^&& p < 0.01, ^&&& p < 0.001.

FIGURE 5

Effects of vancomycin (Vanco) and lycopene (Lyco) administrations on (A) Bcl‐2‐associated X protein (Bax), (B) B‐cell lymphoma 2 (Bcl‐2), (C) ratio of Bax and Bcl‐2, (D) cytochrome c (Cyt‐c) and (E) procaspase‐3 (Procas‐3) levels in kidney tissues of rats. Values are given as mean ± SD (100 fold). CO Control versus others: *p < 0.05, **p < 0.01, ***p < 0.001; Vanco versus others: ^# p < 0.05, ^## p < 0.01, ^### p < 0.001; Vanco + Lyco 5 versus Vanco + Lyco 10: ^& p < 0.05, ^&& p < 0.01, ^&&& p < 0.001.