EFFECT OF DIFFERENT DOSES OF MUMIYO ON DIURETIC RESPONSE IN DOGS FOLLOWING INTRAVENOUS ADMINISTRATION

ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 82 EFFECT OF DIFFERENT DOSES OF MUMIYO ON DIURETIC RESPONSE IN DOGS FOLLOWING INTRAVENOUS ADMINISTRATION Boltabaeva Dilbarkhon Fayzirakhmanovna Senior Teacher of Andijan State Medical Institute, Department of Pharmacology, Clinical Pharmacology, and Medical Biotechnology Abstract. Mumiyo (Shilajit) is a natural herbo-mineral compound long used in traditional medicine for its rejuvenating and adaptogenic effects. This study aimed to evaluate the diuretic activity of Khamzaabad mumiyo in dogs following intravenous administration. Experiments were conducted under controlled conditions, and urine samples were collected hourly for five hours. Mumiyo was administered intravenously at doses of 1–50 mg/kg in 0.9% saline solution. The results showed a clear, dose-dependent increase in urine output and electrolyte excretion, beginning one hour after injection and lasting up to four hours. The diuretic action was primarily associated with reduced tubular reabsorption and enhanced renal excretion of water, sodium, and potassium. These findings suggest that Khamzaabad mumiyo exhibits significant diuretic and natriuretic properties and may be useful for identifying and standardizing Central Asian mumiyo preparations. Keywords: Mumiyo; Shilajit; diuresis; natriuresis; traditional medicine; Khamzaabad mumiyo; intravenous administration; renal function; water–electrolyte balance; adaptogenic compounds Introduction. Traditional medicine (TM) encompasses the knowledge, skills, and practices based on theories, beliefs, and experiences indigenous to different cultures. It is used to maintain health as well as to prevent, diagnose, improve, or treat physical and mental illnesses (1). Consequently, various studies on traditional medicine have been conducted, demonstrating that certain natural medicinal compounds exert beneficial effects on health in numerous diseases (2). Mumiyo is a herbo-mineral exudate with a long history of use in traditional folk medicine. It originates from the mountainous regions of India (3, 5) and Russia (including former USSR regions such as the Urals, Altai, Caucasus, Kazakhstan, the Sayan Mountains, Lake Baikal, Uzbekistan, and Tajikistan). It is also found in other countries, including China, Pakistan, Nepal, Afghanistan, and Tibet (6). Mumiyo—known by various names such as Shilajit, Silajita, Marathi, or Gujarati (in Hindi), Asphalt (in English), Silajatu (in Bengali), Rock Juice (in Tibetan), Conqueror of Mountains (in Sanskrit), Hajar-ul-Musa or Arak al-Jabal (in Arabic), Mumiyo or Mumnaei (in Persian), μούμια (in Greek), Muemu (in Russian), Mumiyo (in German), Mineral Bitumen of Smolensk, Jewish Bitumen, Mineral Wax, and Bragshun—is a natural substance ranging in color from pale brown to dark brownish-black. It has been used for over 3,000 years as a rejuvenating and adaptogenic remedy (4). The origin of mumiyo is explained by three main theories: biological, geological, and biomineralogical. The geological theory suggests that mumiyo is the result of prolonged geological processes. According to the biological theory, it is formed from decomposed plant material or animal excreta under specific physicochemical conditions. The bio-mineralogical concept proposes that mumiyo results from the mechanical contamination of its liquid precursor with mineral substances. Regional factors—including plant species, geological characteristics of rocks and soil, local temperature, humidity, and altitude above sea level—play an important role in influencing its composition and therapeutic properties (8, 9). ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 83 Despite its similar physical characteristics across different regions of the world, these factors affect the composition and proportion of its components. In general, mumiyo consists of organic compounds (60–80%), inorganic compounds (20–40%), and trace elements such as Fe, Ca, Cu, Zn, Mg, Mn, Mo, and P (10). In the 10th century, Ahwazi, in his book Kamel al-Sanae, recommended mumiyo for the treatment of cold headaches, hemoptysis, asthma, and the removal of a dead fetus. Avicenna, the renowned Persian physician, in his famous work The Canon of Medicine, described mumiyo as a highly effective remedy for strengthening the brain, enhancing fertility, and treating a variety of ailments. In the 12th century, the Persian medical text Zakhire Khwarazmshahi by Jorjani recommended mumiyo for inflammation, ulcers, and urinary and prostate disorders (7). Mumiyo has been prescribed in various doses for a wide range of health conditions, including urological and reproductive disorders, jaundice, gallstones, gastrointestinal diseases, splenomegaly, epilepsy, hypersensitivity, nervous disorders, chronic bronchitis, tuberculosis, eczema, anemia, and diabetes (11). However, fungal contamination, particularly with mycotoxins, remains a significant limiting factor for its widespread use in modern medicine (12). Traditional medicine specialists claim that mumiyo is effective against conditions such as loss of libido, kidney stones, bone pain and fractures, osteoarthritis, spondylitis, edema, hemorrhoids, aging, rejuvenation, infections (as an antiseptic), obesity, anorexia, and weight loss (9). Owing to the antiinflammatory, antioxidant, antimutagenic, and immunomodulatory properties of fulvic acid (FA) and humic acid (HA), there is evidence suggesting that mumiyo may serve as a potential agent for cancer prevention (10). Moreover, various doses of mumiyo have shown reductions in blood glucose levels and favorable effects on lipid profiles in rats (13). Additionally, mumiyo extract has been found to enhance nucleic acid synthesis and increase mineral transport into muscle and bone tissues (6). Objective of the Study. In light of numerous studies and claims regarding the therapeutic properties of mumiyo in Traditional Medicine (TM), as well as in the Ayurvedic and Siddha systems of medicine, and considering the lack of comprehensive evaluations on this topic, the present study aims to provide a preliminary assessment of the effects of mumiyo a traditional remedy well known in the ancient medical practices of both the East and the West on diuretic activity in dogs following intravenous administration. Methods of the Study. The effect of Khamzaabad mumiyo on diuresis was investigated in experiments conducted on dogs. The objective of these experiments was to determine the optimal dose of the preparation when administered through different routes. Additionally, information was sought regarding the influence of the administration route on the diuretic effect of mumiyo. The animals were maintained in a temperature-controlled environment and had free access to a standard canine diet and water. Urine samples were collected every hour for five hours. The first urine sample served as a control. After its collection, mumiyo was administered intravenously in various doses, each diluted in 10 mL of 0.9% saline solution. The obtained data are presented in Table 1. Results and Discussion. The data presented in Table 1 indicate that intravenous administration of mumiyo at doses of 1, 5, 10, 25, and 50 mg/kg of body weight produces a diuretic effect beginning approximately one hour after injection and lasting for about four hours. A dose-dependent effect of mumiyo was observed. When administered intravenously, the diuretic response developed within the first hour, and the overall effect was more pronounced than with other routes of administration. ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 84 An analysis of the effects of mumiyo on water–electrolyte balance and renal function indicates that Khamzaabad mumiyo, when administered to rats either as a single dose or over a prolonged period at 50 mg/kg, enhances renal excretion of water, sodium, and potassium. The increase in diuresis appears to result primarily from a reduction in tubular reabsorption. Furthermore, when the extracellular fluid volume was increased in rats through intravenous administration of an isotonic saline solution, the resulting salt and water load caused a marked increase in natriuresis, particularly in the presence of mumiyo. Table 1. Effect of Various Doses of Mumiyo on Diuresis in Dogs Following Intravenous Administration. Dose, route of administration Control period Time after drug administration 1 hour 2 hour 3 hour 4 hour Solvent (i.v.) 43,5 ± 1,0 40,7 ± 1,3 48,2 ± 1,1 46,5± 1,0 45,2 ± 0 Mumiyo 1 mg/kg (i.v.) 73,0 ± 1,7 121,0±2,8 137,0 ±2,8 140,0± 3,1 73,8 ± 2 Mumiyo 5 mg/kg (i.v.) 51,0 ± 1,1 83,0 ± 1,8 173,0 ±4,0 209,0 ±2,3 117,0 ± 1 Mumiyo 10 mg/kg (i.v.) 62,0 ± 1,6 86,0 ± 2,2 213,0 ±3,6 268,0± 6,4 159,0 ± 3 Mumiyo 25 mg/kg (i.v.) 12,8 ± 0,6 128,0±3,5 194,0 ±3,5 186,0 ±2,3 149,0 ± 2 Mumiyo 50 mg/kg (i.v.) 26,0 ± 3,0 109,0±4,0 232,0 ± 9,6 245,0± 8,8 158,0±7,0 *- The change is statistically significant compared to the control. Conclusions 1. All studied types of mumiyo increase diuresis and natriuresis. 2. The presence of this property in Central Asian varieties of mumiyo can be used as a criterion for identification of the preparation. References 1. Qi Z, Kelley E. The WHO Traditional Medicine Strategy 2014-2023: A perspective. Science. 2014;346:S5-S6. 2. “WHO Traditional Medicine Strategy 2014-2023”. World Health Organization Retrieved 2014-0420. 2013. 3. Ghosal S. 2006. Shilajit in Perspective. Narosa Publishing House, New Delhi India. 4. Olivieri MF, Marzari F, Kesel AJ, Bonalume L, Saettini F. Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides. J Hist Neurosci. 2017;26(2):193-215. 5. Wilson E, Rajamanickam GV, Dubey GP,et al.2011. Review on shilajit used in traditional Indian medicine.J Ethnopharmacol 136:1–9 6. Schepetkin I, Khebnikov A, Kwon BS. 2002. Medical drugs from humus matter: focus on mumie.Drug Devel Res57: 140–159 7. Shirbeigi L ZA, Naghizadeh A, Alizadeh Vaghasloo M. The Concept of Temperaments in Traditional Persian Medicine. Trad Integr Med. 2017;2(3):143-56. 8. Frolova N, Kiseleva L, Tatiana. Chemical composition of mumijo and methods for determining its authenticity and quality (a review). Pharma Chem J. 1996;30(8):543-7. 9. Agarwal SP, Khanna R, Karmarkar R, Anwer MK, Khar RK. Shilajit: a review. Phytother Res. 2007;21(5):401-5. ISSN: 2582-4686 SJIF 2021-3.261,SJIF 20222.889, 2024-6.875 ResearchBib IF: 9.948 / 2024 VOLUME-5, ISSUE-11 85 10. Verma A, Kumar N, Gupta L, Chaudhary S. Shilajitin Cancer Treatment: Probable Mode of Action. Int J Pharmaceutic Bio Arch. 2016;7(1):12-6. 11. Stohs SJ, Singh K, Das A, Roy S, Sen CK. 12-Energy and Health Benefits of Shilajit. In: Bagchi D, editor. Sustained Energy for Enhanced Human Functions and Activity. Academic Press; 2017. p. 187-204 12. Ghosal S, Lal J, Singh SK, Goel RK, Jaiswal AK, Bhattacharya SK. The need for formulation of Shilajit by its isolated active constituents. Phytother Res. 1991;5(5):211-6 13. Trivedi N, Mazumdar B, Bhatt J, Hemavathi K. Effect of shilajit on blood glucose and lipid profile in alloxaninduced diabetic rats. Indian J Pharmacol. 2004;36(6):373-6.