Alteration in Oxidative/nitrosative imbalance, histochemical expression of osteopontin and antiurolithiatic efficacy of Xanthium strumarium (L.) in ethylene glycol induced urolithiasis
Introduction
Urolithiasis is one of the important constraints in human and animal health globally since last two decades, irrespective of geographical, racial and cultural boundaries [1], [2]. It is also considered as the third most common problem of the urinary tract with an estimated lifetime risk of around 1–5% in Asia, 8–15% in America and Europe, and 20% in the Middle East countries [3], [4]. The incidence of urolithiasis had been increases in India now a day and two “stone belts” had also been scientifically identified in India [3]. Oxalate, struvite, urate, brushite, cystine were the most commonly reported urolith in man and animal. However, epidemiological studies have shown that majority (70%) of stones commonly contain calcium oxalate (CaC2O4) [1], [2]. In spite of substantial progress in the study of physiology of urolithiasis, its exact mechanism is still not clearly understood. The recent proposed mechanism of stone formation involves urinary supersaturation, crystal nucleation, precipitation, growth, aggregation of crystals and their retention in renal tubular epithelial cells [1], [5]. These processes are modulated by a variety of urinary macromolecules which become incorporated in the growing crystals and eventually constitute organic component or matrix. Osteopontin (OPN) is a negatively charged aspartic acid rich important matrix glycoprotein usually associated with calcium oxalate stone formation [6], [7], [8]. It is mainly present in the loop of Henle and distal nephrons in normal kidneys in animal and humans, but its expression is significantly up regulated after renal damage. Although, OPN is a well known component of stone matrix, but whether it acts as a promoter or inhibitor of stone formation is controversial till date [6], [9], [10].
Modern diagnostic and therapeutic aids like extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy had revolutionized the urological practices but cannot altered the recurrence of stone formation and also have adverse side effects. Pharmaceutical agents like thiazide and citrate diuretics, alkali therapy, allopurinol etc have also limited efficacy in addition to their less tolerability [11]. Indeed, urolithiasis is a multifactorial disease and involves in alteration of several biochemical pathways. Therefore, the present situation demands a newer approach of therapy. Several recent studies have highlighted the effectiveness of medicinal plants and natural compounds for treatment and management of urolithiasis [2], [3], [4], [12], [13], [14], [15]. Moreover, herbal remedies are known to contain multiple constituents, acting through multiple pathways such as antioxidant, analgesic, diuretic, pH neutralising etc. Xanthium strumarium has traditionally been used as an herbal medicine in India, China, Europe, Malaysia and America [16]. The whole plant especially the root, bur and leaves had been reported to possess antiulcerogenic [17], anti-cell proliferative [18], [19], anti-inflammatory and analgesic [20], antidiabetic and hypoglycaemic [16], antiarthritic [21], diuretic and renoprotective [3], [16], antimicrobial [22], antitrypanosomal [23], antihelmintic [24] and anti-plasmodial [25] properties. The bur extract had traditionally been used in the treatment and management of urolithiasis and renal ailments in some parts of India [3] but its antiurolithiatic efficacy was not explored scientifically till now. Hence the study was designed to validate the ethnic practice scientifically in ethylene glycol induced lithiatic rat model, and to explore the possible mechanism of antiurolithiatic effect of xanthium to rationalize its medicinal use.
Section snippets
Animals
The animal care and handling was performed in accordance with the internationally accepted standard guidelines for use of animals and the protocol was approved by institutional animal ethical committee, Indian Veterinary Research Institute, India (vide letter no- F.26-1/2015-16/JDR). Thirty male albino Wistar rats (weighing 150–200 g) were procured from the laboratory animal research division and housed in clean polypropylene cages under controlled temperature 25 ± 2 °C, humidity 45–55% and 12 h
Phytochemical screening
The preliminary phytochemical screening of xanthium revealed positive for alkaloids, flavonoids, triterpenoids, tannins, saponins and proteins, and negative for carbohydrate and coumarin.
Urine and serum biochemistry
All the day 0 parameters of urine and serum biochemistry recorded just before the start of experiment were statistically similar among all the groups; hence the values were not given in the table. Table 1, Table 2 summarise the change in urine and serum biochemistry among different groups at different interval
Discussion
India has been known to be rich repository of medicinal plants since ancient civilization. Xanthium strumarium is a commonly available weed in India and has traditionally been used as a medicinal herb in most parts of India, China, Europe and America [16]. The whole plant especially the root, bur and leaves had been reported to possess antiulcerogenic [17], anti-cell proliferative [18], [19], anti-inflammatory and analgesic [20], antidiabetic and hypoglycaemic [16], antiarthritic [21], diuretic
Conclusion
The present findings demonstrate the curative efficacy of Xanthium strumarium bur in ethylene glycol induced urolithiasis, which might be mediated through inhibiting various pathways involved in renal calcium oxalate formation, antioxidant effect, and potential to inhibit biochemical parameters involving in impairment of renal function and down regulation of matrix glycoprotein, OPN. Therefore, future studies may be established to quantify the active components in the extracts and also to
Acknowledgement
Financial assistance given by the Director, Indian Veterinary Research Institute to undertake this investigation is thankfully acknowledged.
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