90-Days Repeated Dose Oral Toxicity Study of Sharbat-e-Deenar (A Hepatoprotective Unani Herbal Formulation)
Sharbat-e-Deenar (SDR) is a compound Unani pharmacopoeial formulation recommended for the treatment of Waram-e-Kabid (hepatitis), Waram-e-Rahem (uterine inflammation/ Pelvic Inflammatory Diseases), Yarqan-e-Suddi (obstructive jaundice), and Istisqa (ascites). The current study was carried out to investigate repeated dose oral toxicity study of SDR for 90 days in Sprague dawley (SD) rats. SDR was orally administered (gavage) at the doses of 4, 10 and 20 mL/kg bw/day. A periodic observation was performed for mortality, morbidity and any clinical sign of toxicity. Changes in body weight and feed consumption were observed weekly throughout study duration. After the treatment duration of three months, animals were anaesthetized and blood samples were subjected to haematological investigation and serum was subjected to different biochemical estimation. Gross necropsy was performed and internal organs/ tissues were processed for histopathological investigation. Treatment with SDR showed no incidence of mortality and no clinical sign of systemic toxicity. Body weight showed pattern of weight gain except significance decrease at mid and high dose at 13th week of study duration. Feed consumption exhibited a significant decrease as compare to control. Haematology and biochemistry profile found normal except certain isolated changes which was considered toxicologically not significant as the values lies in the normal physiological range. There were no changes observed in the gross necropsy and relative organ weight data of control and SDR treated rats. It is reported that few of the animals showed changes in liver at mid (2.5 times of therapeutic equivalent dose) and high dose (5 times of therapeutic equivalent dose) in SDR treated animals that may be attributed to SDR treatment, however, associated liver function parameters like ALT, AST and ALP did not show any alteration of liver function. Based on the results of this study, it may be indicated that liver may be the target organ for toxicity if SDR is used above recommended therapeutic dose for longer duration.
National Formulary of Unani Medicine (NFUM), Part-I. Central Council for Research in Unani Medicine and for on behalf of Govt. of India. Ministry of Health & F.W. (Deptt. of AYUSH). 2006; pp 222-223.
Shakya AK, Saxena M, Sharma N, Shrivastava S, Shukla S. Hepatoprotective efficacy of Sharbat-e-Deenar against carbon tetrachloride-induced liver damage. J Environ Pathol Toxicol Oncol 2012;31:131-141.
Shakya AK, Shukla S. Protective effect of Sharbat-e-Deenar against acetaminophen-induced hepatotoxicity in experimental animals. J Trad Chin Med 2017;37:387-392.
Moreira D, Teixeira SS, Monteiro MHD, De-Oliveira ACAX, Paumgartten FJR. Traditional use and safety of herbal medicines. Rev Bras Farmacogn 2014;24:248-257.
Kabeeruddin M. Bayaz-e-Kabeer, Vol. 2. Hikmat Book Depot. Hyderabad; p 101.
Khan MA, Urooj M, Thejaswini G, Ahmed SS, Kazmi MH, Husain GM. 180-Days repeated dose oral toxicity study of polyherbal unani formulation: Jawarish Shahi. J Clin Exp Tox 2017;1:21-29.
Moreira D, Teixeira SS, Monteiro MHD, De-Oliveira ACAX, Paumgartten FJR. Traditional use and safety of herbal medicines. Rev. Bras. Farmacogn. 2014; 24(2):248-257.
CPCSEA, Standard Operating Procedures (SOP) for IAEC. New Delhi: Committee for the Purpose of Control and Supervision of Experiments on Animals, 2010.
OECD, Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents, OECD Publishing 1998.
Zillurehman. Dawasazi. Kutub khana Darul-uloom. Meerut 1985; p 136.
EFSA guidance on conducting repeated-dose 90-day oral toxicity study in rodents on whole food/feed. EFSA 2011;9:2438.
Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, and Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. Daru 2012;20:56.
Rezagholizadeh L, Pourfarjam Y, Nowrouzi A, Nakhjavani M, Meysamie A, Ziamajidi N, Nowrouzi PS. Effect of Cichorium intybus L. on the expression of hepatic NF-κB and IKKβ and serum TNF-α in STZ− and STZ+ niacinamide-induced diabetes in rats. Diabetol Metab Syndr 2016;13;8:11.
Haschek WM, Rousseaux CG, Wallig MA. Clinical Pathology. In: Fundamentals of Toxicologic Pathology. Elsevier. 2nd ed. 2010; pp 43-65.
Almanca CCJ et al. Toxicological evaluation of acute and sub-chronic ingestion of hydroalcoholic extract of Solanum cernuum Vell. in mice. J. Ethnopharmacol 2011;138:508-512.
Olson H et al. Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals. Regul Toxicol Pharmacol 2000;32:56-67.
Afshar S, Farshid AA, Heidari R, Ilkhanipour M. Histopathological changes in the liver and kidney tissues of Wistar albino rat exposed to fenitrothion. Toxicol Ind Health 2008;24: 581.
Singh A, Bhat TK, Sharma OP. Clinical Biochemistry of Hepatotoxicity. J Clin Toxicol 2011;S4:001.
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicol 2008;245:194-205.
Rahimi R, Abdollahi M, Farzaei F, Farzaei MH, Memariani Z, Najafi F. Promising effect of Rosa damascena extract on high-fat diet-induced nonalcoholic fatty liver. J Tradit Complement Med 2017;7:508-514.
Fuchs TC, Hewitt P. Biomarkers for drug-induced renal damage and nephrotoxicity-an overview for applied toxicology. AAPS J 2011;13:615-631.
Alam MAA, Javed K, Jafri MA. Effect of Rheum emodi (Revand Hindi) on renal functions in rats. J Ethnopharmacol 2005;96:121-125.
Sellers RS et al. Society of Toxicologic Pathology Position Paper: Organ Weight Recommendations for Toxicology Studies. Toxicol Pathol 2007;35:751-755.
Michael B et al. Evaluation of Organ Weights for Rodent and Non-Rodent Toxicity Studies: A Review of Regulatory Guidelines and a Survey of Current Practices. Toxicol Pathol 2007;35:742-750.
|Issue||Vol. 6, No. 1 (Winter 2021)|
|Hepatoprotection Polyherbal formulation Oral toxicity|
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