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Assessment of Oxidative Stress Effect of Withania somnifera in Rats after 28 Days Repeated Oral Treatment


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1 Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India
     

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Objective: Withania somnifera, a well-known medicinal plant, proved to have a remarkably broad range of therapeutic properties. However, studies evaluating its toxic effects are very scarce. A 28 day repeated oral toxicity study was conducted to evaluate oxidative stress inducing effect, if any, to ascertain its safe use. Method: The present study was designed following the Organization for Economic Cooperation and Development guideline 407. W. somnifera ischolar_main extract was given daily for 28 days through oral route at 30, 300, and 1000 mg/kg dose levels. Results: The results revealed that treated rats exhibited no mortality and toxic symptoms throughout the study period. It was also observed that there was no significant difference in body, organ weights, and feed, water intake in treated rats when compared to control. W. somnifera ischolar_main extract treatment also brought no significant dose-related changes in lipid peroxidation, reduced Glutathione (GSH) content, superoxide dismutase, catalase, GSH-S transferase, and GSH peroxidase enzymes activity in liver, kidney, and brain of treated rats. Conclusion: It can be concluded from the study that 28 days repeated oral treatment of W. somnifera ischolar_main extract found to be devoid of any toxic symptoms and oxidative stress effect.

Keywords

Antioxidant Enzymes, Oxidative Stress, Rat, Withania somnifera Root Powder.
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  • Kuete V. Toxicological Survey of African Medicinal Plants. 1st ed. Elsevier; 2014.
  • Prabu PC, Panchapakesan S, Raj CD. Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera ischolar_mains in Wistar rats. Phytother Res. 2013; 27:1169–78.
  • Khedgikar V, Kushwaha P, Gautam J, Verma A, Changkija B, Kumar A, et al. Withaferin A: A proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone. Cell Death Dis. 2013; 4:e778.
  • McKenna MK, Gachuki BW, Alhakeem SS, Oben KN, Rangnekar VM, Gupta RC, et al. Anti-cancer activity of Withaferin A in B-cell lymphoma. Cancer Biol Ther. 2015; 16:1088–98.
  • Wadegaonkar VP, Wadegaonkar PA. Withanone as an inhibitor of survivin: A potential drug candidate for cancer therapy. J Biotechnol. 2013; 168:229–33.
  • Yang Z, Garcia A, Xu S, Powell DR, Vertino PM, Singh S, et al. Withania somnifera ischolar_main extract inhibits mammary cancer metastasis and epithelial to mesenchymal transition. PLoS One. 2013; 8:e75069.
  • Singh N, Bhalla M, de Jager P, Gilca M. An overview on ashwagandha: A rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011; 8(5Suppl):208–13.
  • Chandra S, Chatterjee P, Dey P, Bhattacharya S. Evaluation of anti-inflammatory effect of ashwagandha: A preliminary study in vitro. Pharmacognosy. 2012; 4:47–9.
  • Gorelick J, Rosenberg R, Smotrich A, Hanuš L, Bernstein N. Hypoglycemic activity of withanolides and elicitated Withania somnifera. Phytochemistry. 2015; 116:283–9.
  • Prakash J, Yadav SK, Chouhan S, Singh SP. Neuroprotective role of Withania somnifera ischolar_main extract in maneb-paraquat induced mouse model of parkinsonism. Neurochem Res. 2013; 38:972–80.
  • Ahmad H, Khandelwal K, Samuel SS, Tripathi S, Mitra K, Sangwan RS, et al. Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats. Drug Deliv. 2015; 28:1–12.
  • Gupta SK, Dua A, Vohra BP. Withania somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal cord and inhibits copper induced lipid peroxidation and protein oxidative modifications. Drug Metabol Drug Interact. 2003; 19:211–22.
  • Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000; 70:57–63.
  • Khan MA, Subramaneyaan M, Arora VK, Banerjee BD, Ahmed RS. Effect of Withania somnifera (Ashwagandha) ischolar_main extract on amelioration of oxidative stress and autoantibodies production in collagen-induced arthritic rats. J Complement Integr Med. 2015; 12:117–25.
  • Bisht P, Rawat V. Antibacterial activity of Withania somnifera against gram-positive isolates from pus samples. Ayu. 2014; 35:330–2.
  • Sahni YP, Sharma M, Pandey GP. Studies on phytochemistry and toxicity of Withania somnifera. Int J Anim Vet Fishery Allied Sci. 2014; 1:12–6.
  • Vaziri ND, Wang XQ, Oveisi F, Rad B. Induction of oxidative stress by glutathione depletion causes severe hypertension in normal rats. Hypertension. 2000; 36:142–6.
  • OECD. OECD Guideline 407. Guideline for the testing of chemicals: Repeated dose 28-day oral toxicity study in rodents. Paris: Organization for Economic Cooperation and Development; 2008.
  • Wills ED. Lipid peroxide formation in microsomes. Relationship of hydroxylation to lipid peroxide formation. Biochem J. 1969; 113:333–41.
  • Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzeneinduced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974; 11:151–69.
  • Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974; 47:469–74.
  • Aebi H. Catalase. In: Packer L, editor. Methods in Enzymology. Orlando: Academic Press; 1984. p. 121–6.
  • Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967; 70:158–69.
  • Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985; 113:484–90.
  • Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974; 249:7130–9.
  • Wills PJ, Asha VV. Acute and subacute toxicity studies of Lygodium flexuosum extracts in rats. Asian Pac J Trop Biomed. 2012; 1:S200–2.
  • Ping KY, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. Biomed Res Int. 2013; 2013:182064.
  • Ho E, Galougahi KK, Liu CC, Bhindi R, Figtree GA. Biological markers of oxidative stress: Applications to cardiovascular research and practice. Redox Biol. 2013; 1:483–91.
  • Prabhakar PV, Reddy UA, Singh SP, Balasubramanyam A, Rahman MF, Indu Kumari S, et al. Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats. J Appl Toxicol. 2012; 32:436–45.
  • Schulke S, Dreidax D, Malik A, Burmester T, Nevo E, Band M, et al. Living with stress: Regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax. Gene 2012; 500:199–206.

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  • Assessment of Oxidative Stress Effect of Withania somnifera in Rats after 28 Days Repeated Oral Treatment

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Authors

P. V. Prabhakar
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India
Utkarsh Addi Reddy
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India
M. F. Rahman
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India
Paramjit Grover
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India
Mohammed Mahboob
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad – 500007, Telangana, India

Abstract


Objective: Withania somnifera, a well-known medicinal plant, proved to have a remarkably broad range of therapeutic properties. However, studies evaluating its toxic effects are very scarce. A 28 day repeated oral toxicity study was conducted to evaluate oxidative stress inducing effect, if any, to ascertain its safe use. Method: The present study was designed following the Organization for Economic Cooperation and Development guideline 407. W. somnifera ischolar_main extract was given daily for 28 days through oral route at 30, 300, and 1000 mg/kg dose levels. Results: The results revealed that treated rats exhibited no mortality and toxic symptoms throughout the study period. It was also observed that there was no significant difference in body, organ weights, and feed, water intake in treated rats when compared to control. W. somnifera ischolar_main extract treatment also brought no significant dose-related changes in lipid peroxidation, reduced Glutathione (GSH) content, superoxide dismutase, catalase, GSH-S transferase, and GSH peroxidase enzymes activity in liver, kidney, and brain of treated rats. Conclusion: It can be concluded from the study that 28 days repeated oral treatment of W. somnifera ischolar_main extract found to be devoid of any toxic symptoms and oxidative stress effect.

Keywords


Antioxidant Enzymes, Oxidative Stress, Rat, Withania somnifera Root Powder.

References





DOI: https://doi.org/10.22506/ti%2F2015%2Fv22%2Fi3%2F137625