Iraqi J Pharm Sci, Vol.19(2) 2010 Lithotripsy of urinary stone by Carum copticum seeds 38 Lithotripsy of Different Urinary Tract Stones by Using Seeds of Carum copticum Ahmed G. Sabar* ,1 * Department of Community Health ,College of Health and Medical Technology, Baghdad,Iraq . Abstract It has been a well-known practice to use seeds and the essential oil of Carum copticum as a strongly antiseptic , antispasmodic , aromatic , bitter , diaphoretic , digestive , diuretic , expectorant and tonic. Also used for cure influenza, asthma, and rheumatoid arthritis. To our knowledge it will be the first time to use the seeds of this herb as a urinary tract stone lithotripsy.This research aimed to the use of these seeds as a lithotripsian against different types of urinary stones and determine the efficiency of these preparation against which types of stone.A liquid solution was prepared from dissolving the seeds powder in cow milk and then concentration this preparation was done by boiling at 100 ° C to reduce the volume of solution to the half.The treatment was given via oral administration for successive 9 days before breakfast. 350 patients with urinary stone of different type took part in this research. All patients were subjected to ultrasonography and intravenous pyelography examinations to localized the position and detect diameter of stone. The above examination and also biochemical tests for diagnosis of stones ingredients were repeated after the administration of treatment and excretion of stone fragments in urine. The results were so promising especially against pure ca- oxalate stone. Key words: Carum copticum; Lithotripsy; Ca-Oxalate stone; mixed stone الخالصة اسزخذِذ ثذٚر ٔجبد إٌخٛح )وّْٛ اٌٍّٛوٟ( ٚوذٌه اٌش٠ٛد اٌط١برح اٌّسزخٍصخ ِٓ اٌجذٚر وّٛاد ِضبدح ٌٍّغص ,ِذرح, ِسبعذح ٌٍٙضُ, ِمشعخ , ٚاسزعٍّذ ا٠ضب ٌعالج اٌجزد ٚاٌسعبي ٚاٌزثٛ ٚاالسٙبي ٚاٌزٙبة اٌّفبصً اٌزِٚبرشِٟ. ٚاسزخذِٕب ثذٚر ٘ذا ٝ اٌّجبرٞ اٌج١ٌٛخ حست ِعٍِٛبرٕب الٚي ِزح فٟ ٘ذا اٌّجبي . ٠ٙذف ٘ذا اٌجحث اٌٝ اسزخذاَ ثذٚر ٔجبد إٌجبد وعالج ٌزفز١ذ حص إٌخٛح إٌٙذ٠خ وعالج ٌزفز١ذ حصٝ اٌّجبرٞ اٌج١ٌٛخ ثبٔٛاعٙب اٌّخزٍفخ, ٚرحذ٠ذ اٌفعب١ٌخ االوجز رجبٖ اٞ ٔٛع ِٓ أٛاع اٌحصٝ . رُ درجخ ِئ٠ٛخ الخزشاي اٌى١ّخ اٌٝ 011اَ ح١ٍت االثمبر ٚرُ رزو١ش إٌم١ع ثغ١ٍبٔٗ اٌٝ رحض١ز ٔم١ع ِٓ ِسحٛق ثذٚر إٌجبد ثبسزخذ ِز٠ضب ِّٓ ٠عبْٔٛ ِٓ ٚجٛد 051ا٠بَ ِززب١ٌخ لجً االفطبر .شبرن فٟ ٘ذٖ اٌذراسخ 9إٌصف . اعطٟ اٌخ١ٍظ عٓ طز٠ك اٌفُ ٌّذح فٛق اٌصٛر١خ( ,ٚاالشعخ اٌٍّٛٔخ ٌزحذ٠ذ ِٛلع ٚحجُ اٌحصٝ , ثُ اٌحصٝ فٟ اٌّجزٜ اٌجٌٟٛ اخضعٛا اٌٝ فحٛصبد اٌسٛٔبر )اٌّٛجبد اجزٞ ٌىبفخ ع١ٕبد اٌجحث فحص االدرار اٌعبَ .اع١ذد ٘ذٖ اٌفحٛصبد ثعذ اسزخذاَ اٌعالج وذٌه اجز٠ذ اٌفحٛصبد اٌجب٠ٛو١ّ١ب٠ٚخ الج فعبي ثىفبءح عب١ٌخ رجبٖ حصبح اٚوشالد عٍٝ اٌحص١بد اٌّزفززخ ٚإٌبسٌخ فٟ االدرار ٌزشخ١ص ِىٛٔبرٙب ح١ث رج١ٓ اْ ٘ذا اٌع اٌجٛربس١َٛ إٌم١خ ٚثذرجخ الً ٌٍحصٛاد ِٓ االٔٛاع االخزٜ . Introduction Renal stones (nephrolithiasis) are concretion composed of crystalline components and organic Matrix [1]. Although the symptomatic presentations may be similar ;the disorder is heterogeneous as to composition and etiology.Today, most urinary stones in patients in most countries are renal stones. About 1-4% of the population is believed to have kidney stones every year in USA and Europe. About 2-5% of population in Asia, 8- 15% in Europe and North America and 20% in saudia Arabia develop kidney stone in their lifetime [2, 3, and 6] . Renal stones tend to recur, and the rate of recurrence is about 75% during 20 years environmental and genetic factors [4-5] . A specific diagnosis for every patient with kidney stones, may give very important information about the stone-formation mechanism and the pharmaceutical manner to prevent recurrent stone formation [5-6] .Carum copticum with herbarium number 293- 0303-1 is a plant in Umbelliferae family with a white flower and small, brownish seeds. This plant is commonly grows in India,Iran,Egypt and Europe [7] .The seeds and especially the essential oil are strongly antiseptic, antispasmodic, diuretic, and used in the treatment of so many diseases.The seeds contains about 4-6% essential oil, of which 45- 55% is thymol [8] , while the essential oil in the dried fruits (2.5-5% ) is dominated by thymol (35-60%) [9] .From South India Carum copticum fruits, almost pure thymol has been isolated (98%) , but the leaf oil was found to be composed of monoterpenoids and sesquiterpenoids: 43%cadinene, 11% longifolene, 5% thymol, 3% camphor and others [9] . The effective components of this 1Corresponding author E- mail : ahmedalqaicy@yahoo.com , ahmed@hotmail.com Received : 16/11/2009 Accepted : 1/8/2010 mailto:ahmedalqaicy@yahoo.com mailto:ahmed@hotmail.com Iraqi J Pharm Sci, Vol.19(2) 2010 Lithotripsy of urinary stone by Carum copticum seeds 39 Plant , responsible for the observed bronchodialatory effect [6] ,despite the availability of modern medication the propensity towards the traditional medications is growing through out the word [7,8] which needs scientific investigation for evaluating the therapeutic effects and their mechanism of action. Indeed no acute toxicity data were available for Carum copticum ,although animal studies of putative beneficial effect of this plants seeds involved the use of a dose of 500mg/kg body weight in mice and rat without morbidity or mortality ascribable to the herb, suggesting that the oral LD50 of Carum copticum (fruit/seeds) is likely to be higher than that figure [9] . The present study was carried out to determine the role of Carum copticum seeds as a herbal medication for treatment urinary tract stones. Materials and Methods The study of effects of Carum copticum seeds as a lithotripsian agent was carried out in 2008 on (350) patients diagnosed by specialist physician in private clinic from different sites of Iraq (Baghdad,Diala,Mousol) and the experimental part was undertaken during the period (2001-2008). Materials Seeds of Carum copticum (other Latin name : Trachyspermum ammi ), were collected from local market in Baghdad, identified under expert guidance ,taxonomy was performed by national herbarium of Iraq at 1997,depended on Ayurvedic pharmacopoeia of India (API) [10] , and kew herbarium [11] , liquid milk, sugar. The dose normally recommended in traditional Ayurvedic use is 3-6 gm / day , presumably being 3 gm once or twice a day [12] . Also this dose was documented in Arabic antique manuscript (Tathkarat Daood AL-Antaky) [13] . Methods Before started giving the preparation we obtained the written consent of the patients who included in the study; (15gm) of seeds were ground to a very fine powder.(Total dose for each patients taken with in 9 days) ;(5gm) of grounded seeds were boiled with 150 ml of liquid cow milk and 25 gm sugar, until half of the volume was obtained; the preparation was kept cool [13] ;This preparation divided to ( 3 ) equal doses, each patients was given single dose a day before breakfast for a period of 3 days ; This procedure was repeated for remainder (10gm) of grounded seeds ; Ultrasonography (U /S) and Intravenous pyelography (IVP), were performed pre-, and post treatment to be sure of curing urinary tract from any stone; Urinary tract stones were of different sizes ranging from 5mm and 1.2 cm and they were seen in the kidney (renal stone) at upper pole calyx, mid renal part and lower pole calyx, also they were seen in the ureter (uretral stones) , and finally they were seen inside urinary bladder (vesical stones) . In addition general urine examination (GUE) was done for all patients ; Qualitative analysis of stone / fragments passed after herbal treatment, a procedure described by Hodgkinson [14] , was employed to figure out the chemical constituent of urinary stone Results The present study included (350) patients with different urinary tract stones were treated with liquid extract of Carum copticum seeds. Table 1 : Chemical constituent of stones Patients age range(years) % No. of patients Type of stone (20-45) 48,57 170 Pure Ca-oxalate 20-50)) 28.57 100 (Ca-oxalate/uric acid) mixed stone (22-50) 22,86 80 Ca-oxalate/) Hydroxyapatite) mixed stone 100% 350 Total Table 2 : Lithotripsy events Table 3 : Duration of lithotripsy % No. of lithotripsed stone No. of patients Type of stone 100 170 170 Pure ca-oxalate 53 53 100 (Ca-oxalate./ Uric acid) mixed stone 31.25 25 80 ( Ca-oxalate./ hydroxyapatite) mixed stone 350 Total Time (days) Type of stone 2-7 Pure ca-oxalate 7-12 Ca-oxa./uric acid))Mixed stone. 7-15 Ca-oxalate./hydroxyapatite) Mixed stone. Iraqi J Pharm Sci, Vol.19(2) 2010 Lithotripsy of urinary stone by Carum copticum seeds 40 Table 4 : Response the types of stones to the treatment with Carum copticum * H.S: Highly Significant Discussion The results of this study including the investigation of the efficiency of Carum copticum seeds (liquid solution), locally prepared on urinary stone among (350) patients.The results present in table (1) showed that pure ca- oxalate consist the larger percentage among types of stones. Since a (170) patients out of (350) patients (48.57%) have a pure ca-oxalate urinary stone.Results of table (1) revealed that (28.57), (22.86) of patients got mixed stone (ca- oxalate\uric acid) and (ca-oxalate \hydroxyapatite) respectively.The results cleared out in table (2) indicated that the local preparation of Carum copticum seeds have a good affectivity on ca-oxalate stones , since a hundred percent of this type of urinary stone had been lithotripsed , comparing to (53%) for mixed (ca-oxalate\uric acid) and (31.25%) for mixed (ca-oxalate\hydroxyapatite) . Recently in India had successfully purified an anticalcifying protein from the seeds of Carum copticum using oxalate depletion assay and deciphered its inhibitory activity against ca-oxalate crystals growth .The antilithiatic potential of Carum copticum was confirmed by its ability to maintain renal functioning, reduce renal injury and decrease crystal excretion in urine and retention in renal tissue [15] .It was obvious from the results presented in table (3) that pure ca-oxalate required the minimum duration to complete lithotripsy. While mixed stone of both types required a longer time to complete lithotripsy. The response of types of stone was indicated in table (4) which showed that pure ca-oxalate was the most affected types of stones by the treatment with Carum copticum seeds compared with other two types of urinary stones mainly (ca- oxalate\uric acid) mixed stone and (ca- oxalate\hydroxyapatite) mixed stone. On the other hand type two of stone (ca-oxalate\uric acid) mixed stone was affected by treatment with Carum copticum seeds more than the mixed stone (ca-oxalate\hydroxyapatite). Our results confirmed the antilithiatic properties of Carum copticum seeds that authorized by many researchers [16-19] . Biostatistical analysis (Binomial-test and Z-test) confirmed these results. It could be argued for that the effect of herb extract (crude extraction) is depending totally on chemical structure of urinary tract stones, also it is clear from the results presented in table (4) that ca-oxalate whenever existed as one of the constituent of urinary tract stones it will provoke or stimulate the action of herbs seeds extract, in other word ca-oxalate is decisive component of urinary tract stone that encourage lithotripsy whenever Carum copticum seeds extract are available.In this view, mixed stones which are either (ca-oxalate\uric acid) or (ca- oxalate\hydroxyapatite) showed different response to the treatment with Carum copticum seeds extraction and that in our view is corresponding to the amount of ca-oxalate present in the mixture .In general, the lithotripsic effects of Carum copticum seeds against urinary tract stones were mentioned by Arabic scientist sheikh Dawood Antaki (about 1008 A. H) [13] . Conclusion Thus, the present study suggests the potential of Carum copticum seeds in lithotripsy of urinary stone, especially calcium oxalate and forms the basis for the development of antilithiatic drug interventions against urolithiasis. Acknowledgment The author is grateful to Dr. Nabeel Fadel , Dr. Nasseer Abed Agha, and Dr. Akram Mohd Al-mahdawy, for help in the diagnosis of the caseas. Thank also to Dr. Zuhair Nouman Al-Ani a Professor of pharmacogenetic for his scientific advices. References 1. Pak CYC. Kidney stones. Williams Textbook of Endocrinology 1992; 1519-36. 2. Pak CYC.Kidney stones. Lancet 1998; 351: 1797-801. 3. Kamoun A, Daudon M, Abdelmoula J, Hamzaoui M,Chouachi B, Houissa T, Zghal A, Ben Ammar S, Belkahia C, Lakhoua R. Urolithiasis in Tunisian Children. Pediater Nephrol 1999; 13(9):920-5. 4. Gault MH, Chafe L. Relationship of frequency, age, sex, stone weight and composition in 15 624 stones. J Urol 2000; 64 (2): 302-7. 5. 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