Acute, Sub-Acute and Genotoxicity Assessment of Cocculus hirsutus Hydroalcoholic Leaf Extract in Wistar Rats

Jump To References Section

Authors

  • College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram – 522502, Andhra Pradesh ,IN
  • College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram – 522502, Andhra Pradesh ,IN
  • College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram – 522502, Andhra Pradesh ,IN
  • College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram – 522502, Andhra Pradesh ,IN
  • College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram – 522502, Andhra Pradesh ,IN
  • Vignan Institute of Pharmaceutical Technology, Duvvada, Visakhapatnam – 534202, Andhra Pradesh ,IN

DOI:

https://doi.org/10.18311/ti/2021/v28i2/26814

Keywords:

Biochemical, Cocculus hirsutus, DNA Damage, Histopathological, Oxidative Stress, Toxicity

Abstract

Acute (0, 500, 1000 and 2000 mg/kg) and 28-day (0, 100, 200 and 400 mg/kg) toxicity assessments of Cocculus hirsutus hydroalcoholic leaf extract (CH-Ex) were performed in Wistar rats consistent with OECD guidelines 423 and 407 respectively. Average body weights were recorded, blood and biochemical parameters were analyzed and histopathological studies were performed. At doses (12.5–100 μg/ml), genotoxicity assessments were conducted on pUC 19 plasmid by evaluating DNA damage protection. Acute toxicity assessment categorized CH-Ex as safe and non-toxic (category 5). The 28-day toxicity assessments showed no significant (p>0.05) changes in body weights, hematology and histopathology. At 400 mg/kg females exhibited a slight decline in SGPT, creatinine and BUN levels, while male rats exhibited a slight enhancement of SGOT and ALP levels (p<0.05). CH-Ex exhibited strong ability to protect DNA damage from oxidative stress in a dose-dependent manner.

Downloads

Download data is not yet available.

Published

2021-05-31

How to Cite

Sankar Gorla, U., Koteswara Rao, G. S. N., Kulandaivelu, U., Reddy Alavala, R., Prasad Panda, S., & Kolakota, R. (2021). Acute, Sub-Acute and Genotoxicity Assessment of <i>Cocculus hirsutus</i> Hydroalcoholic Leaf Extract in Wistar Rats. Toxicology International, 28(2), 177–186. https://doi.org/10.18311/ti/2021/v28i2/26814

Issue

Section

Original Research
Received 2021-01-24
Accepted 2021-03-10
Published 2021-05-31

 

References

Logesh R, Das N, Adhikari-Devakota A, Devakota HP. Cocculus hirsutus (L.) W. Theob. (Menispermaceae): A review on traditional uses, phytochemistry and pharmacological activities. Medicines. 2020; 7(11):69. PMid: 33182572 PMCid: PMC7696458. https://doi. org/10.3390/medicines7110069 DOI: https://doi.org/10.3390/medicines7110069

Marya H, Bothara B. Ethanopharmacological properties of Cocculus hirsutus (L.) Diels-a review. Int J Pharm Sci Rev Res. 2011; 7(1):108–12.

Madhavan V, Ullah MS, Gurudeva MR, Yoganarasimhan SN. Pharmacognostical studies on the leaves of Cocculus hirsutus (Linn.) Diels-Chilahinta, an Ayurvedic drug. Indian J Nat Prod Resour. 2010; 1(1):38–43.

Devi P, Meera R, Muthuppandi R, Ragumathi, Babu DD. Phyto-physico chemical evaluation of leaves of Cocculus hirsutus. Asian J Res Chem. 2010; 3(1):51–3.

Viqaruddin A, Tahir RJ. Studies on the chemical constituents of Cocculus hirsutus. J Chem Soc Pak. 1986; 8:537–40.

Rasheed T, Khan MN, Zhadi SS. Hirsutine: A new alkaloid from Cocculus hirsutus. Pak J Nat Prod. 1991; 54:582–4. https://doi.org/10.1021/np50074a037 DOI: https://doi.org/10.1021/np50074a037

Viqaruddin A, Iqbal S. Haiderine: A new isoquinoline alkaloid from Cocculus hirsutus. J Nat Prod. 1993; 2:105–9. https://doi.org/10.1080/10575639308043793 DOI: https://doi.org/10.1080/10575639308043793

Thakare SP, Jain HN, Patil SD, Upadhyay UM. Hepatoprotective effect of Cocculus hirsutus on bile duct ligation-induced liver fibrosis in Albino Wister rats. Bangladesh J Pharmacol. 2009; 4(2):126–30. https://doi.org/10.3329/bjp.v4i2.2980 DOI: https://doi.org/10.3329/bjp.v4i2.2980

Masilamani G, Showkath A, Subbalakshmi V. Study on karappan (Eczema). J Res Ayu Sci. 1981; 2:109–21.

Mon MM, Maw SS, Oo ZK. Screening of antioxidant, anti-tumor and antimicrobial herbal drugs/diets from some Myanmar traditional herbs. Int J Biosci Biochem Bioinforma. 2011; 1:142–7. https://doi.org/10.7763/IJBBB.2011.V1.26 DOI: https://doi.org/10.7763/IJBBB.2011.V1.26

Badole S, Patel N, Bodhankar S, Jain B, Bhardwaj S. Antihyperglycemic activity of aqueous extract of leaves of Cocculus hirsutus (L.) Diels in alloxan-induced diabetic mice. Indian J Pharmacol. 2006; 38(1):49–53. https://doi.org/10.4103/0253-7613.19853 DOI: https://doi.org/10.4103/0253-7613.19853

Thavamani BS, Mathew M, Dhanabal SP. Cocculus hirsutus: Molecular docking to identify suitable targets for hepatocellular carcinoma by in silico technique. Pharmacogn Mag. 2016; 12(s3):s350–2. PMid: 27563224 PMCid: PMC4971956. https://doi.org/10.4103/0973-1296.185769 DOI: https://doi.org/10.4103/0973-1296.185769

Ganapaty S, Dash GK, Subburaju T, Suresh P. Diuretic, laxative and toxicity studies of Cocculus hirsutus aerial parts. Fitoterpia. 2002; 73(1):28–31. https://doi.org/10.1016/S0367-326X(01)00345-8 DOI: https://doi.org/10.1016/S0367-326X(01)00345-8

Sangameswaran B, Jayakar B. Anti-diabetic and spermatogenic activity of Cocculus hirsutus (L.) Diels. Afr J Biotechnol. 2007; 16(10):1212–6.

Gadapuram TK, Murthy JSN, Rajannagari RR, Kandati V, Choda PK, Shukla R. Nephroprotective activity of Cocculus hirsutus leaf extract in 5/6 nephrectomized rat model. J Basic Clin Physiol Pharmacol. 2013; 24(4):299–306. PMid: 23729561. https://doi.org/10.1515/jbcpp-2013-0007 DOI: https://doi.org/10.1515/jbcpp-2013-0007

Rastogi B, Tiwari U, Dubay A, Bawara B, Chauhan NS, Saraf DK. Immunostimulant activity of Cocculus hirsutus on immunosuppressed rat. Pharmacologyonline. 2008; 3:38–57.

Brahmam P, Sunita K. Phytochemical investigation and In vitro antimalarial activity of Acalypha indica (L.) and Cocculus hirsutus (L.) from Prakasam district, Andhra Pradesh, India. Biomed Pharmacol J. 2018; 11(4):2123–34. https://doi.org/10.13005/bpj/1592 DOI: https://doi.org/10.13005/bpj/1592

Sravankumar G, Rajesh K, Sengottuvelu S, Chiranjeev G, Hareesh D. Evaluation of analgesic and antiinflammatory activity of methanolic extract of Cocculus hirsutus leaves. Int Res J Pharm. 2011; 2(12):230–4.

Choi J, Su-Jung R, Kui-Jin K, Hyung-Min K, Hee-Chu C, Boo-Yong L. Single, 14-day and 13-week repeated dose toxicity studies of daily oral Gelidium elegans extract administration to rats. Molecules. 2018; 23(1):217. PMid: 33406634. https://doi.org/10.3390/ molecules23010217 DOI: https://doi.org/10.3390/molecules23010217

OECD. 2001. Test guideline 423. Acute oral toxicity- Acute toxic class method. In OECD Guidelines for the Testing of Chemicals. Organisation for Economic Cooperation and Development, Paris. p. 1-14.

Eziuche AU, Akubugwo IE, Ude VC, Gilbert J, Ekeanyanwu B. Toxicological evaluation of phyto chemical characterized aqueous extract of wild dried Lentinus squarrosulus (Mont.) mushroom in rats. Toxicol Res.2019; 35(2):181–90. PMid: 31015900 PMCid: PMC6467362 https://doi.org/10.5487/TR.20 19.35.2.181 DOI: https://doi.org/10.5487/TR.2019.35.2.181

OECD. 1995. Test guideline 407. Repeated dose 28-day oral toxicity study in rodents. In OECD Guidelines for the Testing of Chemicals. Organisation for Economic Cooperation and Development, Paris. p. 1-8.

Devi N, Sangeetha R. Acute and sub-acute toxicity assessment of the hydroalcoholic extract of Madhuca longifolia leaves in wistar rats. J Herbs Spices Med Plants. 2019; 25(3):287–97. https://doi.org/10.1080/10 496475.2019.1611687 DOI: https://doi.org/10.1080/10496475.2019.1611687

Adeolu AA, Matthew OA, Olufunso OO. Effects of some plants of the spurge family on haematological and biochemical parameters in rats. Vet Arhiv. 2007; 77(1):29–38.

Ibrahim KE, Al-Mutary MG, Bakhiet AO, Khan HA. Histopathology of the liver, kidney and spleen of mice exposed to gold nanoparticles. Molecules.2018; 23(8):1848. PMid: 30044410 PMCid: PMC6222535. https://doi.org/10.3390/molecules23081848 DOI: https://doi.org/10.3390/molecules23081848

Khan MS, Qais FA, Ahmad I, Hussain A, Alajmi MF. Genotoxicity inhibition by Syzygium cumini (L.) seed fraction and rutin: Understanding the underlying mechanism of DNA protection. Toxicol Res. 2018; 7(2):156–71. PMid: 30090571 PMCid: PMC6062347. https://doi.org/10.1039/C7TX00269F DOI: https://doi.org/10.1039/C7TX00269F

Ghorbanpour M, Varma A. Medicinal plants and environmental challenges. Springer, Switzerland. 2017. 1–23. https://doi.org/10.1007/978-3-319-68717-9_1 DOI: https://doi.org/10.1007/978-3-319-68717-9_22

WHO. WHO global report on traditional and complementary medicine 2019. World Health Organisation, Geneva. 2019. 1–228.

Parasuraman S. Toxicological screening. J Pharmacol Pharmacother. 2011; 2(2):74–9. PMid: 21772764 PMCid: PMC3127354. https://doi.org/10.4103/0976-500X.81895 DOI: https://doi.org/10.4103/0976-500X.81895

Saganuwan SA. Toxicity studies of drugs and chemicals in animals: An overview. Bulg J Vet Med. 2017; 20(4):291–318. https://doi.org/10.15547/bjvm.983 DOI: https://doi.org/10.15547/bjvm.983

Unuofin JO, Otunola GA, Afolayan AJ. Evaluation of acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less in Wistar rats. J Integr Med. 2018; 16(5):335–41. PMid: 30007829. https://doi.org/10.1016/j.joim.2018.07.003 DOI: https://doi.org/10.1016/j.joim.2018.07.003

Earnest OE, Ihekwereme CP, Ilodigwe EE. Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdiscip Toxicol. 2018; 11(1): 5–12. PMid: 30181707 PMCid: PMC6117820. https://doi.org/10.2478/intox-2018-0001 DOI: https://doi.org/10.2478/intox-2018-0001

Rania HA, Basha WA, Khalil WF. Subacute toxicity of Nerium oleander ethanolic extract in mice. Toxicol Res. 209; 35(3):233–9. PMid: 31341552 PMCid: PMC6629440. https://doi.org/10.5487/TR.2 019.35.3.233 DOI: https://doi.org/10.5487/TR.2019.35.3.233

Raina P, Chandrasekaran CV, Deepak M, Aggarwal A, Ruchika KG. Evaluation of sub-acute toxicity of methanolic/aqueous preparation of aerial parts of O. sanctum in Wistar rats: Clinical, haematological, biochemical and histopathological studies. J Ethno pharmacol. 2015; 175:509–17. PMid: 26456329. https://doi.org/10.1016/j.jep.2015.10.015 DOI: https://doi.org/10.1016/j.jep.2015.10.015

Kianoush S, Balali-Mood M, Mousavi SR, Shakeri MT, Dadpour B, Moradi V, Sadeghi M. Clinical, toxicological, biochemical and hematologic parameters in lead exposed workers of a car battery industry. Iran J Med Sci. 2013; 38(1):30–7.

Zohair A, Ahmed U, Walayat S, Ren J, Martin DK, Moole H, Koppe S, Yong S, Dhillon S. Liver function tests in identifying patients with liver disease. Clin Exp Gastroenterol. 2018; 11:301–7. PMid: 30197529 PMCid: PMC6112813. https://doi.org/10.2147/CEG. S160537 DOI: https://doi.org/10.2147/CEG.S160537

Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010; 2(4):170–3.

Nassar I, Pasupati T, Judson TP, Segarra I. Histopathological study of the hepatic and renal toxicity associated with the co-administration of imatinib and acetaminophen in a preclinical mouse model. Malays J Pathol. 2010; 32(1):1–11.

Ramaraj T, Ramya G, Gogulramnath M. Antigenotoxic and apoptotic activities of essential oil of Atalantia monophyla Correa. Indian J Pharmacol. 2016; 48(6):720–4. PMid: 28066114 PMCid: PMC5155477. https://doi.org/10.4103/0253-7613.194866 DOI: https://doi.org/10.4103/0253-7613.194866

Zahra S, Soltani F, Moein M. Insight into DNA protection ability of medicinal herbs and potential mechanisms in hydrogen peroxide damages model. Asian Pac J Trop Biomed. 2018; 8(2):120–9. https://doi.org/10.4103/2221-1691.225616 DOI: https://doi.org/10.4103/2221-1691.225616

Peter S, Witt KL, Revanna P, Smith-Roe SL, Dismukes J, Lloyd DG, Engelward BP, Sobol RW. Next generation high throughput DNA damage detection platform for genotoxic compound screening. Sci Rep. 2018; 8:2771. PMid: 29426857 PMCid: PMC5807538. https://doi. org/10.1038/s41598-018-20995-w DOI: https://doi.org/10.1038/s41598-018-20995-w

Qing-Ping H, Xin-Ming C, Dong-Lin H, Liang- Liang Z. Chemical composition, antioxidant, DNA damage protective, cytotoxic and antibacterial activities Cyperus rotundusrhizomes essential oil against foodborne pathogens. Sci Rep. 2017; 7:45231. PMid: 28338066 PMCid: PMC5364420. https://doi.org/10.1038/srep45231 DOI: https://doi.org/10.1038/srep45231