Date Published: September 12, 2019
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia
Author(s): Yixin Ke, Kaihang Yu, Weiliang Zeng, Guojun Lian.
To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats.
Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days.
The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. PFE could protect the kidney against acute renal toxicity induced by CdCl2.
Cadmium (Cd) is designated as an endocrine disruptor/endocrine disrupting chemical (EDC), a potential toxicant metal derived from horticultural and industrial sources1. It is a pollutant for most human foods because it has a high soil-plant transmission rate, making diet a main source of contact2. The level of Cd toxic in kidney, lung and testis tissues has been determined3. A previous study reported that many transporters play important roles in the accumulation of Cd in kidney tissue, including metallothionein, Cd binding proteins containing thiol (-SH) groups and divalent metal ion transporter 14. Cd accumulates in kidney to produce reactive oxygen species (ROS), which leads to inflammation, oxidative stress, glomerular dysfunction and programmed cell death5, and interferes with basic elements such as calcium and zinc6. The S1 and S2 segments of the proximal convoluted tubule are the target sites of renal tissue toxicant, leading to renal dysfunction7. In addition, Cd is considered as the cause of lipid peroxidation and is generally considered to be the major cause of the deleterious effects on membrane-dependent function8, which makes the kidney more vulnerable to cadmium. Due to the lack of adequate methods for treating cadmium nephrotoxicity, there is an increasing interest in the use of antioxidants to prevent the kidney from the toxicity of Cd.
Pyracantha fortune fruit extract (PFE) is characterized as an excellent antioxidant11, rich in polyphenols such as rutin, hexose compound, and polymeric (epicate)-catechin (proanthocyanidin 2, PB2)10. A growing number of evidences support the biological properties of PFE against antioxidants, anti-tumor and protection of liver damage11–13. Several studies in animal models showed that Cd accumulates mainly in kidney tissue19,20. Some studies showed that Cd therapy leads to kidney atrophy21, while other studies reported kidney hypertrophy after Cd therapy22. However, it is still unclear whether the damage caused by heavy metals can be alleviated by P fortuneana. In this study, the effects of PFE on kidney injury in CdCl2-injected rats were investigated. The results showed that even if CdCl2 levels in the renal tissue were high, pretreatment with PFE in rats would significantly reduce the levels. Increasing kidney weights and the loss of body weight in CdCl2-injected rats observed in this investigation, was consistent with the results of previous reports5,23. PFE pretreatment in rats prevented these changes. We also examined markers that denote renal function and found that CdCl2 induced an increase in serum uric acid, urea and creatinine, and the results showed renal insufficiency. PFE pretreatment in rats decreased these indicators levels of renal dysfunction. Histological results confirmed the effect mentioned earlier, whether it was the destructive effects of CdCl2 and the protective effects of PFE24. PFE pretreatment in rats helped protect the kidneys from this damage, for example, by chelating CdCl2. Our results reinforced the hypothesis that PFE can attenuate CdCl2 accumulation and renal damage in kidney tissues of rats treated with CdCl2.
The pretreatment of PFE suggested protective roles against CdCl2-induced toxicity of kidney. The antioxidant and anti-apoptosis activity of PFE can achieve these antioxidant protection effects via the Nrf2/Keap 1 pathway. Therefore, the use of PFE may be beneficial for renal toxicity caused by CdCl2.