Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Ashok  Kumar; Pragi; Amit Sharma; Varun Kumar

doi:10.18231/j.joapr.2024.12.1.82.92

Authors

Ashok Kumar Department of Pharmacy, Faculty of Medical, Paramedical and Allied Health Sciences, Jagannath University, Jaipur, Rajasthan 303901
Pragi Department of Pharmacy, Jagannath University Bahadurgarh, Haryana 124507
Amit Sharma Department of Pharmacy, Jagannath University Bahadurgarh, Haryana 124507
Varun Kumar Department of Pharmacy, Jagannath University Bahadurgarh, Haryana 124507

DOI:

https://doi.org/10.18231/j.joapr.2024.12.1.82.92

Keywords:

Vitis vinifera, Biochemical parameters, Hepatoprotective, Nephroprotective, Histopathology

Abstract

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl₄-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl₄. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

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References

Liu MZ, Zhang YL, Zeng MZ, He FZ, Luo ZY, Luo JQ, Wen JG, Chen XP, Zhou HH, Zhang W. Pharmacogenomics and herb-drug interactions: merge of future and tradition. Evid Based Complement Alternat Med, 2015, 321091. (2015).

Giannini EG, Farinati F, Ciccarese F, Pecorelli A, Rapaccini GL, Di Marco M, Benvegnù L, Caturelli E, Zoli M, Borzio F, Chiaramonte M, Trevisani F.Italian Liver Cancer (ITA.LI.CA) group. Prognosis of untreated hepatocellular carcinoma. Hepatology, 61, 184–190 (2015)

Gillessen A, Schmidt HHJ.Silymarin as supportive treatment in liver diseases: A narrative review. Advances in Therapy, 37, 1279–1301(2020).

Jose SP, Im K, Ratheesh M, Singh S, Santosh S, Sandya S, Kumar G, Parmod C.Nephro-protective effect of a novel formulation of unopened coconut inflorescence sap powder on gentamicin induced renal damage by modulating oxidative stress and inflammatory markers. Biomedicine and Pharmacotherapy, 85, 128–135 (2017)

Karie S, Launay-Vacher V, Deray G, Isnard-Bagnis C, Renale DT. Medicaments. Nephrologieet Therapeutique, 6, 58–74 (2010)

Schortgen F. Nephrotoxicity and medications drug and renal toxicity. Reanimation,14, 436–441(2005)

Morales-Alvarez MC.Nephrotoxicity of antimicrobials and antibiotics. Advances in Chronic Kidney Disease, 27, 31–37 (2020)

Abongwa M, Rageh AG, Arowolo O, Dawurung C, Oladipo O, Atiku A, Okewole P, Shamaki D.Efficacy of Sennaoccidentalis in the amelioration of tetracycline induced hepato- and Nephro-toxicities in rabbits. Toxicology Letters, 196, S207 (2010)

Im DS, Shin HJ, Yang KJ, Jung SY, Song HY, Hwang HS, Gil HW.Cilastatin attenuates vancomycin-induced nephrotoxicity via P-glycoprotein. Toxicology Letters, 277, 9–17 (2017)

Abu-Serie MM, Habashy NH, Maher AM. In vitro anti-nephrotoxic potential of Ammi visnaga, Petroselinum crispum, Hordeum vulgare, and Cymbopogon schoenanthus seed or leaf extracts by suppressing the necrotic mediators, oxidative stress and inflammation. BMC Complement Altern Med, 19, 149. (2019).

Gupta G, Kuppachi S, Kalil RS, Buck CB, Lynch CF, EngelsEA.Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States. American Journal of Transplantation, 18, 245–252 (2018)

Hikino H, Kiso Y, Wagner H, Fiebig M. Antihepatotoxic actions of flavonolignans from Silybummarianum fruits. PlantaMedica, 50, 248–250 (1984)

Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybummarianum) for the therapy of liver disease. American Journal of Gastroenterology,93,139–143(1998)

AbouZid S. Silymarin, Natural Flavonolignans from Milk Thistle. In: Venketeshwer R, editor. Phytochemicals-A Global Perspective of Their Role in Nutrition and Health. Rijeka: Croatia InTech, 255–272 (2012)

Pietrangelo A, Borella F, Casalgrandi G, Montosi G, Ceccarelli D, Gallesi D, Giovannini F, Gasparetto A, Masini A. Antioxidant activity of silybinin vivo during long-term iron overload in rats. Gastroenterology, 109, 1941–1949 (1995)

Bosisio E, Benelli C, Pirola O. Effect of the flavanolignans of Silybummarianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacological Research, 25, 147–154 (1992)

Carini R, Comoglio A, Albano E, Poli G. Lipid peroxidation and irreversible damage in the rat hepatocyte model. Biochemical Pharmacology, 43, 2111–2115 (1992)

Sonnenbichler J, Goldberg M, Hane L, Madubunyi I, Vogl, S. Zetl I. Stimulatory effect of silibinin on the DNA synthesis in partially hepatectomized rat livers: Non-response in hepatoma and other malign cell lines. Biochemistry and Pharmacology, 35, 538–541(1986)

Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clinical Drug Investigation.22, 51–65 (2002)

Liang ZC, Owens CL, Zhong GY, ChengLL.Polyphenolic profiles detected in the ripe berries of Vitisviniferagermplasm. Food Chemistry, 129, 940–950 (2011)

Xia EQ, Deng GF, Guo YJ, Li HB.Biological activities of polyphenols from grapes. International Journal of Molecular Sciences, 11, 622–646 (2010)

Yang J, Martinson TE, Liu RH.Phytochemical profiles and antioxidant activities of wine grapes. Food Chemistry, 116,332–339(2009)

Bitsch R, Netzel M, Frank T, Strass G, Bitsch I.Bioavailability and biokinetics of anthocyanins from red grape juice and red wine. Journal of Biomedicine and Biotechnology, 5, 293–298 (2004)

Bub A, Watzl B, Blockhaus M, Briviba K, Liegibel U, Müller H, Pool-Zobel BL, Rechkemmer G.Fruit juice consumption modulates antioxidative status, immune status and DNA damage. Journal of Nutritional Biochemistry,14, 90–98 (2003)

Garcia-Alonso M, Minihane AM, Rimbach G, Rivas-Gonzalo JC, Pascual-Teresa S. Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma. Journal of Nutritional Biochemistry,20, 521–529 (2009)

Jang MS, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM.Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275, 218–220 (1997)

Del CA, Cacciorro AF, Fenu PAM, Piga A.Polyphenols, colour and antioxidant activity changes in four Italian red wines during storage. ActaAlimentaria Hung,39, 192–210 (2010)

Liang ZC, Wu BH, Fan PG, Yang CX, Duan W, Zheng X, Liu C, Li S.Anthocyanin composition and content in grape berry skin in Vitisgermplasm. Food Chemistry, 111, 837–844(2008)

Nikfardjam MSP, Márk L, Avar P, Figler M, Ohmacht R.Polyphenols, anthocyanins, and trans-resveratrol in red wines from the Hungarian villany region. Food Chemistry, 98, 453–462 (2006)

Pirniyazov AZ, Abdulladzhanova NG, Mavlyanov SM, Kamaev FG, Dalimov DN.Polyphenols from Vitisvinifera seeds. Chemistry of Natural Compounds,39, 349–355 (2003)

Tagliazucchi D, Verzelloni E, Bertolini D, Conte A.In vitro bio-accessibility and antioxidant activity of grape polyphenols. Food Chemistry, 120, 599–606(2010)

Valdez LB, Alvarez S, Zaobornyj T, Boveris A.Polyphenols and red wine as antioxidants against peroxynitrite and other oxidants. Biological Research, 37, 279–286 (2004)

Vita JA.Polyphenols and cardiovascular disease: Effects on endothelial and platelet function. American Journal of Clinical Nutrition, 81,Suppl.292S–297S (2005)

Mesbahzadeh B, Salarjavan H, Samarghandian S, Farkhondeh T. Chlorpyrifos with age-dependent effects in cardiac tissue of male rats. CurrMolPharmacol,14, 894-899 (2021)

Wen J, Chen Z, Wang S, Zhao M, Wang S, Zhao S, Zhang X. Age-related reductions in the excitability of phasic dorsal root ganglion neurons innervating the urinary bladder in female rats. Brain Res, 1752:147251 (2021)

Kim KW, Cho HJ, Khaliq SA, Son KH, Yoon MS. Comparative analyses of mTOR/Akt and muscle atrophy-related signaling in aged respiratory and gastrocnemius muscles. Int J MolSci,21:2862 (2020)

Kader MSA, Hamad AM, Alanazi MT, Alanazi AH, Ali R, Foudah A, Alqarni MH. Characterization and hepatoprotective evaluation of sesquiterpenes and diterpenes from the aerial parts of Juniperussabina L. Saudi Pharm J,27, 920–929 (2019)

Edwards CRW, Bouchier IAD. Davidson’s Principles andPractice Medicine. UK: Churchill Livingstone Press (1991)

Varley H, Alan HG. Tests in renal disease. In: Practical Clinical Biochemistry, vol. 1123. William Heinemann Medical Book Ltd., London. 1123 (1984)

Braun HP, Deneke U, Rittersdorf W. Analytical performance of reflotroncreatin kinase reagent carriers compared with the CK NAC-method. Clin. Chem,33, 988 (1987)

Lee GH, Lee HY, Choi MK, Chung HW, Kim SW, Chae HJ.Protective effect of Curcuma longaL. extract on CCl4-induced acute hepatic stress. BMC Research Note,10, 77 (2017)

Abdus SM, Mofijul SMI, Gaihre YK, Shah AL, Singh U, Sarkar IMU, Sanabria J, Biswas JC. Rice yields and nitrogen use efficiency with different fertilizers and water management under intensive lowland rice cropping systems in Bangladesh. Nutrient Cycling in Agroecosystems,106, 143–156 (2016)

Molehin OR, Oloyede OI, Idowu KA, Adeyanju AA, Olowoyeye AO, Tubi OI, Komolafe OE, GoldAS.White butterfly (Clerodendrumvolubile) leaf extract protect against carbon tetrachloride-induced hepatotoxicity in rats. Biomedicine and Pharmacotherapy,96, 924–929 (2017)

Ustuner D, Colak E, Dincer M, Tekin N, Donmez DB, Akyuz F, Colak E, Kolac UK, Entok E, Ustuner MC.Post treatment effects of OleaeuropaeaL.leaf extract on carbon tetrachloride-induced liver injury and oxidative stress in rats. Journal of Medicinal Food, 00(0),1–6 (2018)

Snyder R, Andrews LS. Toxic effects of solvents and vapors. In: Toxicology: the Basic Science of Poisons, Klassen CD (Ed.), New York: McGraw-Hill (1996)

Zafar R, Ali SM. Anti-hepatotoxic effects of root and root callus extracts of Cichoriumintybus L. Journal of Ethnopharmacology, 63, 227–231(1998)

Lin CC, Shieh DE, Yen MN. Hepatoprotective effects of fractions Ban-zhi-lian of experimental liver injuries in rats. J Ethnopharmacol, 56, 193-200 (1997)

Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AA, VernekarSN.Markers of renal function tests. North American Journal of Medical Sciences, 2, 170–173 (2010)

Pocock G, Richards CD.Human physiology. The basis of Medicine (3rd ed). Oxford University Press (2006)

Adelman RD, Spangler WL, Beasom F, Ishizaki G, Conzelman GM. (1981). Frusemide enhancement of neltimicin nephrotoxicity in dogs. Journal of Antimicrobial Chemotherapy, 7, 431–440 (1981)

Satyapal US, Kadam VL, Ghosh R. Hepatoprotective activity of Livobond a polyherbal formulation against CCl4 –induced hepatotoxicity in rats. International Journal of Pharmacy,4, 472–476 (2008)

Zhang MQ, Ren X, Zhao Q, Yue SJ, Fu XM, Li X, Chen KX, Guo YW, Shao CL, WangCY.Hepatoprotective effects of total phenylethanoid glycosides from Acanthus ilicifolius L. against carbon tetrachloride-induced hepatotoxicity. Journal of Ethnopharmacology, 256, 112795 (2020)

Vladimir-Knezevic S, Cvijanovíc O, Blazekovic B, Kindl MBM. Hepatoprotective effects of Micromeriacroaticaethanolic extract against CCl4-induced liver injury in mice. BMC Complementary and Alternative Medicine, 15, 233(2015)

Popovic D, Kocic G, Katic V, Zarubica A, Velickovic LJ, Nickovic V. P.et al.Anthocyanins protect hepatocytes against CCl4-induced acute liver injury in rats by inhibiting pro-inflammatory mediators, polyamine catabolism, lipocalin-2, and excessive proliferation of Kupffer cells, Antioxid. Basel, 8, 451(2019)

Li L, Li W, Kim YH, LeeYW.Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice. Experimental and Toxicologic Pathology, 65, 73–80 (2013)