Nephroprotective role of bromelain against oxidative injury induced by aluminium in rats

https://doi.org/10.1016/j.etap.2020.103509Get rights and content

Highlights

  • Aluminium-induced kidney dysfunction and hyperlipedimia.

  • Aluminium induced lipid peroxidation and disturbance in antioxidant defense system.

  • Aluminium treatment led to histological and immunohistochemical changes

  • Bromelain is a novel strategy in attenuating the harmful effects of aluminium.

  • Bromelain inhibits oxidative stress induced by aluminium.

Abstract

The present study was designed to investigate the nephroprotective effect of bromelain against oxidative stress stimulated by aluminium chloride in rats. Rats were grouped as follows; group one was used as control while groups 2, 3 and 4 were treated orally with bromelain (250 mg/kg, daily), aluminium chloride (AlCl3; 34 mg/kg BW, every other day) and bromelain plus AlCl3 for 30 days, respectively. Administration of AlCl3 caused a significant reduction in rats’ body and kidney weights, and increased Al accumulation in kidney tissue. Also, AlCl3 treatment elevated thiobarbituric acid reactive substances, hydrogen peroxide, kidney functions biomarkers levels and lactate dehydrogenase activity. While enzymatic (SOD, CAT, GPx, GR, GST) and non-enzymatic (GSH) antioxidants, protein content, and alkaline phosphatase activity were significantly decreased. In addition, significant alterations in lipid and protein profiles were detected. Furthermore, histopathological and immunohistochemical variations were seen in kidney sections supporting the obtained biochemical changes. Otherwise, rats supplemented with bromelain singly declined lipid peroxidation and improved most of the studied parameters. Moreover, rats pretreated with bromelain followed by AlCl3 intoxication showed significant alleviation in lipid peroxidation, antioxidant status and biochemical indices with respect to AlCl3 treated group. Conclusively, bromelain has beneficial protective effects and has the capability to counteract the toxic influence of AlCl3. So, bromelain might represent a novel approach in the therapy of metal toxicity because of its antioxidant and chelating properties.

Introduction

Aluminium (Al) is one of the environmental factors that cause hazardous impacts to many organs (Oteiza et al., 1993). Al has different forms that are utilized in water cleaning, food and fuel additives, medicinal products, cooking utensils made of aluminium and electrical instruments (Inouse et al., 1988; Scancar and Milacic, 2006; Krewski et al., 2007), causing serious health problems in human and animal (Willhite et al., 2014). The major source of Al is due to its ingestion in food such as corn, yellow and processed cheese, baking powder, and flour (Lione, 1983; Abbasali et al., 2005). Exposure to Al induced toxicity on different biological systems including blood constituents, nervous, respiratory, skeletal, and immune systems (Willhite et al., 2014). Aluminium exerts its toxicity via different mechanisms that include increasing blood-brain barrier permeability, interference with phosphorylation-dephosphorylation processes, and alternating ions metabolism with subsequent free radicals’ production and disruption of second messenger system (Agarwal et al., 1996). Also, AlCl3 induced disturbances in kidney function and architectures accompanied with elevation in renal oxidative stress and inflammation suggesting strong pro-oxidant activity of AlCl3 (Al Dera, 2016a, 2016b, Balgoon, 2019; Mokrane et al., 2020). Al salts may affect the enzyme activity of hexokinase, phosphatases, phosphodiesterase, and phosphooxydase (Ochmanski and Barabasz, 2000; Szilagyi et al., 1994). Moreover, Al generates reactive oxygen species (ROS) (Mohamed and Abd El-Moneim, 2017), resulting in oxidative deterioration of lipids, proteins, and DNA.

Great interest is directed to many plants because of their antioxidant potential, among them Ananas comosus (Pineapple) which belongs to Bromeliaceae family. Ananas comosus is largely cultivated in the equatorial regions worldwide and has wide beneficial known effects as antioxidant, anticancer, anti-inflammatory and anti-platelet impact. Ananas comosus stem extract is an inexpensive byproduct waste rich in complex enzymes identified by bromelain which are so important in some clinical applications especially tumor growth modulation, wound healing, anti-inflammatory effect, anti-diarrhea and digestive aid (Koh et al., 2006; Chaisakdanugull et al., 2007; Bitange et al., 2008). Also, bromelain has an immense antioxidant effect in ameliorating the renal toxicity induced by dichlorvos (Agarwal et al., 2017). Furthermore, it has a chelating potential for combating lead toxicity and oxidative stress and represents a new approach in the treatment of metal toxicity and metabolic disorders (Al-Otaibi et al., 2015). Bromelain has many commercial uses including the food industry, pharmaceutical products (as cosmetics) as well as supplements for health promotion (Uhlig, 1998; Walsh, 2002; Ketnawa and Rawdkuen, 2011). Prolonged oral use of bromelain is safe and it can be absorbed easily in the human intestinal tract without any decomposition or activity loss (Chobotova et al., 2010; Pavan et al., 2012). Hence, the present investigation was prepared to evaluate the protective efficiency of bromelain in alleviating nephrotoxicity stimulated by aluminium in male rats.

Section snippets

Chemicals

Bromelain extracted from the stems of pineapple, was purchased from Holland and Barrett, England. Aluminium chloride (AlCl3) utilized here was bought from Aldrich Chemical Company (Milwaukee, USA).

Experimental design

Twenty-eight male Wister rats (150–170 g) were obtained from the Faculty of Medicine, Alexandria University, Alexandria, Egypt. The protocol was approved by the local University Committee in conformity with the ethics and guidelines of the National Institutes of Health. Rats were distributed in cages

General health

None of the AlCl3-intoxicated rats showed signs of morbidity or mortality during the study. Body and absolute kidney weights of AlCl3-treated rats were significantly decreased as compared to control. However, bromelain supplementation alleviated this reduction with respect to AlCl3 exposed group. Bromelain alone did not cause any significant change (Table 1).

Aluminium concentration in rat kidney

The Al concentration in the kidney of rats was measured after one month of oral AlCl3 administration (Fig. 1). The level of Al in the

Discussion

In the current investigation, the antagonistic role of bromelain from Ananas comosus stem against AlCl3 induced oxidative injury and biochemical perturbations was studied. Little findings have been pointed out the efficiency of bromelain from Ananas comosus stem as natural products for overcoming heavy metals toxicity. Absorption of aluminium via the gastrointestinal and the respiratory tracts is known to disrupt oxidants/antioxidant balance in tissues, leading to various biochemical and

Conclusion

In conclusion, the present results pointed out that aluminium chloride has the potency to cause renal dysfunction via oxidative injury, alterations in antioxidant defense system, enzyme activities, and biochemical parameters. Furthermore, bromelain from Ananas comosus stem administration in combination with aluminium attenuates its toxicity by quenching, chelating and detoxifying the free radicals. So, bromelain had a powerful antioxidant role in alleviating Al toxicity by potentiating

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Fatma M. El-Demerdash: Conceptualization, Methodology. Hoda H. Baghdadi: Investigation. Ansam B. Al Mhanna: Writing - original draft.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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