The effect of activated charcoal on adenine-induced chronic renal failure in rats
Introduction
Administration of sorbents, i.e. compounds that bind other chemicals onto their outer surfaces, and within their interstices (Ash, 2009) has been suggested as either an alternative or supplementary treatment for patients with chronic kidney disease (CKD). They have been shown to remove waste products such as urea, indoxyl sulfate (IS) and other urinary toxins, and augment the dialysis process (Schulman, 2012, Winchester and Ronco, 2010, Yamamoto et al., 2011). One of these sorbents is charcoal (Cooney, 1995, Olson, 2010, Vaziri et al., 2013), which is produced by heating pulverized carbonaceous substances to temperatures of 600–900 °C, followed by “activation” using either steam or hot air to erode the internal surfaces of the product and thereby increase its adsorptive surface area. Typical surface areas for activated charcoals are about 800–1200 m2/g. Thus, a 50-g dose of activated charcoal has an adsorptive surface area equivalent to about seven football fields or 5183 m2, and “Superactivated” charcoals may have a surface area of 2800–3500 m2/g and can adsorb greater quantities of drugs (Olson, 2010). Charcoal, in various forms, administered with low protein diets has been reported to control effectively some uremic symptoms in patients with different stages of renal disease, and this is achieved through the binding of urea and other urinary toxins to charcoal, and its excretion with feces, creating a concentration gradient for continued diffusion of these toxins (Ash, 2009). Scavenging of urinary toxins by charcoals has also been proposed (Fujii et al., 2009). The beneficial effect was reported especially in elderly patients with end-stage renal disease (ESRD) (Musso et al., 2010). Recently, Schulman et al. reported that the use of activated charcoal (AC) and other alternative agents, which are capable of blocking the actions of profibrotic cytokines, such as transforming growth factor-beta (TGF-β), can either halt or prevent the development of CKD in early stages (Schulman, 2012).
The adenine-induced chronic renal failure (CRF) rat model, first reported by Yokozawa et al. (1986), produces metabolic abnormalities resembling CKD in humans, which may include azotemia, accumulation of uremic toxins, metabolic imbalances of amino acids and electrolytes, and hormonal imbalances (Yokozawa et al., 1986). Pathologically, renal tissue of adenine-fed rats show lesions in proximal and distal tubules, as well as in glomeruli (Ali et al., 2013a). In mammalian metabolism, excess adenine becomes a significant substrate for xanthine dehydrogenase (CAS serial number: EC 1.2.3.2), which can oxidize adenine to 2,8-dihydroxyadenine (DHA) via an 8-hydroxyadenine intermediate (Wyngaarden and Dunn, 1957). However, the very low solubility of DHA leads to its precipitation in kidney tubules (de Vries and Sperling, 1977, Yokozawa et al., 1986). The complex inflammatory phenomena associated with this model depend, at least in part, on NF-κB activation (Okabe et al., 2013).
Experimentally, several drugs and natural products have been used to ameliorate the effects of adenine-induced CRF. These include gum acacia (Ali et al., 2010), fucoidan derivatives from Laminaria japonica (Wang et al., 2012), ergone (ergosta-4, 6, 8(14), 22-tetraen-3-one) (Zhao et al., 2012) and lanthanum carbonate (Damment et al., 2011). As far as we are aware, there is no published report on the effect of dietary charcoal on adenine-induced CRF, and this is the subject of the present investigation. Since AC derivatives have been shown to be beneficial in CKD, mechanistic studies in CKD animal models are warranted.
Section snippets
Animals
This project was reviewed and approved by the Animal Research Ethics Committee of Sultan Qaboos University. All procedures involving animals and their care were conducted in conformity with international laws and policies (EEC Council directives 86/609, OJL 358, 1 December, 12, 1987; NIH Guide for the Care and Use of Laboratory Animals, NIH Publications No. 85-23, revised 1996).
Forty-eight male Wistar rats, initially weighing 150–155 g, were obtained from the Sultan Qaboos University Animal
Body and kidney weight changes
As shown in Fig. 1, control rats grew by about 8% during the 28 days of treatment. However, treatment with adenine (0.75%, w/w) for the same period resulted in a significant reduction in body-weight (amounting to about 28%) and a significant increase of the kidney/body weight ratio. AC treatment at concentrations of 5%, 15% and 20%, w/w, slightly decreased the growth of the rats, but neither changed the absolute nor the relative kidney weight significantly when compared with the control.
Discussion
This is, as far as we are aware, the first study on the effect of AC on an adenine-induced model for CRF. Adenine induced various pathological signs of CRF in the rats, as shown in previously published work (Ali et al., 2013a, Iida et al., 2013). AC at a concentration of 20%, w/w, in the feed for 28 days (but not at concentrations of 5% and 15%) significantly protected rats against several functional, histopathological and biochemical changes induced by adenine, as evidenced by restoration of
Conclusion
This work shows that simultaneous treatment of rats with adenine and AC (20%, w/w, in the feed for 28 days) produced a broad, dose-dependent, nephro-protective action in adenine-induced CRF. The use of 20% AC alone was without any overt adverse effects on the treated animals. The protective mechanism of AC appears to be through its adsorption of uremic toxins and also its antioxidant effect.
The adsorbent AC has been very commonly employed in human and veterinary medicine for years as a general
Conflict of Interest
The authors declare that there are no conflicts of interest.
Acknowledgement
This work was financially supported by a grant from The Research Council of Oman (RC/Med/Phar/10/01). We thank the staff of the Animal House of SQU for caring for the rats.
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