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D. Toczek et al.
controls the blood pressure. The blood clotting is also the Ca
2 +
-dependent process
[2]. Moreover, calcium ions, as the second messenger, control processes related to
the muscle contraction and nerve impulse transmission [3, 4]. There are hundreds
of known proteins binding calcium but the most important is Calmodulin, the special protein dedicated for Ca
2 +
, which after binding with calcium ions changes the
conformation and performs different functions. The only available form of Ca
2 +
are dietary sources. The metabolism of Ca
2 +
is regulated by three mechanisms:
intestinal absorption, renal reabsorption, and bone turnover [3]. Beside the proper
homeostasis of Ca
2 +
in the organism, there are also pathological changes in the
calcium economy as osteoporosis or nephrolithiasis. The osteoporosis is related to
calcium losses in the biggest reservoir of calcium—bones, while the urolithiasis
involves the formation of calcium deposit in kidneys. In almost 80 % cases kidney
stones contain calcium oxalate as a fundamental compound. Moreover, nephrolithiasis is the worldwide problem, which is usually more common for men than for
women [5]. Lewandowski and Rodger [6] divide factors causing nephrolithiasis
on: environmental factors (climate, occupation), physiochemical factors (urine volume, urinary concentration of oxalate and other elements) and dietary patterns and
nutrients. Nowadays, medicine offers only few methods of the treatment of kidney
stones: traditional-surgery or, less invasive extracorporeal shock wave lithotripsy
(ESWL), percutaneous stone removal (PCNL), and endourological stone treatment
[7]. The possible treatment constitutes only instrumental techniques and no active
drugs or active substances which prevent this disease are available. The only offered
drug for patients are those causing increase of urine flow or controlling colic pain
[8]. Unfortunately nephrolithiasis is a recurrent disease and about 75 % of patients
suffer the recurrence within 10 years. Therefore it is important to develop new more
efficient preventative therapies, which can inhibit the formation of kidney stones or
possess properties of dissolution of calcium oxalate deposits. The possible approach
constitutes modeling the potential inhibitors forming calcium oxalate crystals. On
the other hand there are available compounds directly influencing the calcium oxalate formation (inhibitory or dissolution effect) e.g. citrate. It should be noted that
compounds possessing dissolution properties of calcium oxalate cannot interfere
too much into the whole calcium economy.
Crystallographic data show that the preferred donor for calcium cation are oxygen atoms, while the complexes with nitrogen or sulfur as ligands are a rarity [9].
Hence, potential structures applied for dissolution of kidney stones should contain,
in their skeleton, many oxygen atoms. We must remember however that there are
many different oxygen atoms with regard to their chemical environment (e.g. hydroxyl, acid, ester, ether, glycosidic and others) and their ability to bind calcium will
depend on this factor.
The extract from Rubia tinctorum L. is rich in hydroxyanthraquinones and these
compounds were used in the kidney stones treatment. Unfortunately it contains also
lucidin, one of anthraquinones which exhibit the genotoxic activity [10]. Anthraquinones are polyphenols and they have ability to interact with calcium ions (as will be
described later in this chapter). Due to their condensed aromatic polycarbon structure there is a risk of genotoxity. There are some other polyphenols without con-
D. Toczek et al.
controls the blood pressure. The blood clotting is also the Ca
2 +
-dependent process
[2]. Moreover, calcium ions, as the second messenger, control processes related to
the muscle contraction and nerve impulse transmission [3, 4]. There are hundreds
of known proteins binding calcium but the most important is Calmodulin, the special protein dedicated for Ca
2 +
, which after binding with calcium ions changes the
conformation and performs different functions. The only available form of Ca
2 +
are dietary sources. The metabolism of Ca
2 +
is regulated by three mechanisms:
intestinal absorption, renal reabsorption, and bone turnover [3]. Beside the proper
homeostasis of Ca
2 +
in the organism, there are also pathological changes in the
calcium economy as osteoporosis or nephrolithiasis. The osteoporosis is related to
calcium losses in the biggest reservoir of calcium—bones, while the urolithiasis
involves the formation of calcium deposit in kidneys. In almost 80 % cases kidney
stones contain calcium oxalate as a fundamental compound. Moreover, nephrolithiasis is the worldwide problem, which is usually more common for men than for
women [5]. Lewandowski and Rodger [6] divide factors causing nephrolithiasis
on: environmental factors (climate, occupation), physiochemical factors (urine volume, urinary concentration of oxalate and other elements) and dietary patterns and
nutrients. Nowadays, medicine offers only few methods of the treatment of kidney
stones: traditional-surgery or, less invasive extracorporeal shock wave lithotripsy
(ESWL), percutaneous stone removal (PCNL), and endourological stone treatment
[7]. The possible treatment constitutes only instrumental techniques and no active
drugs or active substances which prevent this disease are available. The only offered
drug for patients are those causing increase of urine flow or controlling colic pain
[8]. Unfortunately nephrolithiasis is a recurrent disease and about 75 % of patients
suffer the recurrence within 10 years. Therefore it is important to develop new more
efficient preventative therapies, which can inhibit the formation of kidney stones or
possess properties of dissolution of calcium oxalate deposits. The possible approach
constitutes modeling the potential inhibitors forming calcium oxalate crystals. On
the other hand there are available compounds directly influencing the calcium oxalate formation (inhibitory or dissolution effect) e.g. citrate. It should be noted that
compounds possessing dissolution properties of calcium oxalate cannot interfere
too much into the whole calcium economy.
Crystallographic data show that the preferred donor for calcium cation are oxygen atoms, while the complexes with nitrogen or sulfur as ligands are a rarity [9].
Hence, potential structures applied for dissolution of kidney stones should contain,
in their skeleton, many oxygen atoms. We must remember however that there are
many different oxygen atoms with regard to their chemical environment (e.g. hydroxyl, acid, ester, ether, glycosidic and others) and their ability to bind calcium will
depend on this factor.
The extract from Rubia tinctorum L. is rich in hydroxyanthraquinones and these
compounds were used in the kidney stones treatment. Unfortunately it contains also
lucidin, one of anthraquinones which exhibit the genotoxic activity [10]. Anthraquinones are polyphenols and they have ability to interact with calcium ions (as will be
described later in this chapter). Due to their condensed aromatic polycarbon structure there is a risk of genotoxity. There are some other polyphenols without con-