Background: Majoon-e-Kundur (MK) is a compound Unani formulation used in Taqteer-ul-Baul (Dribbling of urine), Salasul- Baul (Urinary incontinence), Baul Filfarash (Nocturnal enuresis), Surat-e-Inzal (Premature ejaculation) and Zof-e-Masana (weakness of urinary bladder). However, toxicity studies on MK have not been carried out for its long-term use.
Objective: The present study was carried out to study the 180 days repeated dose toxicity of MK in rats.
Materials and methods: The study was carried out on Sprague Dawley (SD) rats of both sexes. Animals were divided into two groups (n = 15). MK was administered at a limit dose of 2000 mg/kg bw/day p.o. for 180 days. After completion of 180 days blood samples were collected for hematological and biochemical analysis and animals were sacrificed, and organs were harvested for relative organ weight determination followed by histopathological evaluation.
Results: Animals in groups treated with MK did not show any abnormal behavior or clinical signs indicative of systemic toxicity. There was no toxicologically significant alteration observed in body weight, feed intake, hematological and biochemical parameters, relative organ weights and histopathological findings of control and MK treated rats of either sex.
Conclusion: There were no toxicologically significant alterations with respect to clinical signs of toxicity, body weight gain and feed intake, hematology, clinical chemistry, organ weight, gross necropsy and histopathological findings in MK treated rats at a dose of 2000 mg/kg bw as compared to control group. It may be concluded based on the above observations that MK is safe up to the limit dose tested in rats.
CPCSEA. Standard Operating Procedures (SOP) for IAEC. New Delhi: Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA); 2010 pp. 41-42.
US-FDA. Guidance for Industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals 2010 pp. 1-30. Available online from http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Schedule Y. Drugs and Cosmetics Act. Requirements and guidelines for permission to import and/or manufacture of new drugs for sale or to undertake clinical trials. Available online from http://rgcb.res.in/uploads/2014/07/Schedule-Y. pdf.
Gad SC. Repeat dose toxicity studies. In: Gad SC, editor. Preclinical development handbook - toxicology. Hoboken, NJ: John Wiley & Sons Inc; 2008 pp. 213-221.
Gribaldo L. Haematotoxicology scientific basis and regulatory aspects. Altern. Lab. Anim. 2002;30:111-113.
Devarbhavi H. An update on the drug-induced liver injury. J Clin. Exp. Hepatol. 2012;2:247-259.
EMEA. Non-clinical guideline on drug-induced hepatotoxicity. London, UK: European Medicines Agency; 2008pp. 1-16.
Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J. Clin. Toxicol. 2011;S4:001.
Ramaswamy RS, Prathyusha N, Saranya R, Sumathy H, Mohanavalli KT, Priya RJ, et al. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats. BMC Complement. Altern. Med. 2012;12: 190.
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology 2008; 245:194-205.
Fuchs TC, Hewitt P. Biomarkers for drug-induced renal damage and nephrotoxicity–an overview for applied toxicology. AAPS J. 2011;13:615-631.
Sellers RS, Morton D, Michael B, Roome N, Johnson JK, Yano BL, et al. Society of Toxicologic Pathology position paper: organ weight recommendations for toxicology studies. Toxicol. Pathol. 2007;35:751-755.
Michael B, Yano B, Sellers RS, Perry R, Morton D, Roome N, et al. Evaluation of organ weights for rodent and nonrodent toxicity studies: a review of regulatory guidelines and a survey of current practices. Toxicol. Pathol. 2007;35:742- 750.
Husain GM, Ahmed SS, Azhar M, Siddiqui JI, Waheed MA, Kazmi MH. Comparative toxicity study on classical and modified version of Jawarish Jalinoos (a traditional Unani formulation) in rats. Integr Med Res. 2017;6(1):66-78.