Using Pomegranate Peel Extract to Change the Adverse Effect of Ethephon by Enhancing its Antioxidant, Anti-inflammatory, and Anti-apoptotic Effects in Rats

Main Article Content

Hamid Mahmood Abdullah Daabo
https://orcid.org/0000-0001-9861-9407

Abstract

Organophosphorus insecticide and growth regulator namely Ethephon (2-chloroethylphosphonic acid) are widely used as a ripening process accelerator and a cultivation duration inhibitor. Pomegranate extract (PPE) has recently been taken into consideration due to its pharmacological effects especially those associated with renal diseases. Thus, this study aims to investigate the possible protective effect of PPE against ethephon-induced nephrotoxicity in rats. In this study four groups of adult male rats were divided into control group, PPE 400 mg/kg group, Ethephon 250 mg/kg group, and finally, PPE + Ethephon group (treated with the same dose of PPE group and Ethephon group). In the current study, kidney function parameters (KIM-1, creatinine, and urea) along with oxidative stress markers, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2–related factor 2 (Nrf2), glutathione (GSH) and its correlated enzymes, nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) were estimated. Additionally, mediators of renal inflammation: interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB) were measured. Apoptotic biomarkers (Bax, caspase 3, and Bcl2) in addition to renal histopathological data were also investigated. Results revealed that Ethephon elicited a significant increase in oxidation markers and reduced antioxidant levels, accompanied by oxidative renal tissue injury. Consequently, administration of Ethephon was reported to provoke secretion of the pro-inflammatory mediators. Moreover, histopathological results showed that deformities in the renal tissues were noticed which is attributed to Ethephon exposure. Interestingly, co-administration of PPE and Ethephon resulted in significantly ameliorated the biochemical and histopathological alterations produced by Ethephon. Current results propose the potential effect of PPE in the protection of renal tissue from Ethephon induced nephrotoxicity in rats.

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1.
Using Pomegranate Peel Extract to Change the Adverse Effect of Ethephon by Enhancing its Antioxidant, Anti-inflammatory, and Anti-apoptotic Effects in Rats. Baghdad Sci.J [Internet]. 2022 Oct. 1 [cited 2024 Apr. 18];19(5):1045. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/6144
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How to Cite

1.
Using Pomegranate Peel Extract to Change the Adverse Effect of Ethephon by Enhancing its Antioxidant, Anti-inflammatory, and Anti-apoptotic Effects in Rats. Baghdad Sci.J [Internet]. 2022 Oct. 1 [cited 2024 Apr. 18];19(5):1045. Available from: https://bsj.uobaghdad.edu.iq/index.php/BSJ/article/view/6144

References

Hodjat M, Baeeri M, Rezvanfar MA, Rahimifard M, Gholami M, Abdollahi M. On the mechanism of genotoxicity of ethephon on embryonic fibroblast cells. Toxicol Mech Met. 2017; 27:173-180.

Yehya Kamal Al-Bayati. Estimation of some Organophosphorus Pesticides Using Carbon Paste Electrode Coupled with Molecularly Imprinted Polymers: Baghdad Sci.J. 2018; 15(3): 328-344.

Bhadoria P, Nagar M, Bahrioke V, Bhadoria AS. Effect of ethephon on the liver in albino rats: A histomorphometric study. Biomed J. 2015; 38:421-7.

Mokhtari T, Hussein Osman H-E, El-Meghawry El-Kenawy A, Dashti N. Ameliorative effect of virgin olive oil against nephrotoxicity following sub-chronic administration of ethephon in male rats. J Tradit Comp Med. 2020;10(5):487–495.

Wang S, Jin H, Tang Q, Fu J, Ren Z, Peng C, Shang L, Hao W, Wei X. The effect of ethephon on immune system in male offspring of mice. Environ Toxicol Pharmacol. 2017; 49:119-123.

Abd Eldaim MA, Tousson E, El Sayed IET, Awd WM. Ameliorative effects of Saussurea lappa root aqueous extract against Ethephon-induced reproductive toxicity in male rats. Environ Toxicol. 2019; 34:50-159.

Porter GA, Bennett WM. Nephrotoxic acute renal failure due to common drugs. Am J Physiol. 1981;241(1): F1-8.

Shirwaikar A, Issac D, Malini S. Effect of Aerva lanata on cisplatin and gentamicin models of acute renal failure. J Ethnopharmacol. 2004;90(1):81-6.

Hosohata K. Role of Oxidative Stress in Drug-Induced Kidney Injury. Int J Mol Sci. 2016;17(11):1826.

Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003 Oct 20;22(47):7265-79.

Van Pelt J, Makni Ayadi F, Rebai T, Elfeki A. Protective effects of Mentha piperita L. leaf essential oil against CCl4 induced hepatic oxidative damage and renal failure in rats. Lipids Health Dis. 2018;17(1):9.

Kaya Y, Bas O, Hanci H, et al. Acute renal involvement in organophosphate poisoning: histological and immunochemical investigations. Ren Fail. 2018;40(1):410-415.

Abdel-Daim MM, Khalil SR, Awad A, Abu Zeid EH, El-Aziz RA, El-Serehy HA. Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway to Restore Kidney Tissue from Cobalt-Mediated Oxidative Injury and Inflammation in Rats. Nutrients. 2020; 12:1031.

Daabo HMA. Protective Effect of Costus Speciosus Rhizome Extract Against Cytotoxicity Induced by Tramadol in Mice. Biointerface Res Appl Chem. 2021;11(2):9530 – 954.

Wei XL, Fang RT, Yang YH, Bi XY, Ren GX, Luo AL, Zhao M, Zang WJ. Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med. 2015; 15:389.

Baradaran Rahimi V, Ghadiri M, Ramezani M, Askari VR. Antiinflammatory and anti-cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies. Phytoth Res. 2020;34(4):685-720.

Sreekumar S, Sithul H, Muraleedharan P, Azeez JM, Sreeharshan S. Pomegranate fruit as a rich source of biologically active compounds. Biomed Res Int. 2014; 2014:686921.

Niwano Y, Saito K, Yoshizaki F, Kohno M, Ozawa T. Extensive screening for herbal extracts with potent antioxidant properties. J Clin Biochem Nutr. 2011 Jan;48(1):78-84.

Cerdá B, Llorach R, Cerón J J, Espín J C, Tomás-Barberán F A. Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eu J Nutr. 2003; 42:18–28.

Bassiri-Jahromi S. Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Onc Rev. 2018;12(1):345.

Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. N Y Sci J. 2011;4(3):27–41.

Emam NM, Anjum S, Okail HA, Ibrahim MAR, Ahmad T. Pomegranate peel extract protects against carbon tetrachloride-induced nephrotoxicity in mice through increasing antioxidants status. Biomed Rep. 2020;13(3):13.

Chinnappan SM, George A, Thaggikuppe P, Choudhary Y, Choudhary VK, Ramani Y, et al. Nephroprotective Effect of Herbal Extract Eurycoma longifolia on Paracetamol-Induced Nephrotoxicity in Rats. Evid Based Complement Alternat Med. 2019; 2019:4916519.

Vučić V, Grabež M, Trchounian A, Arsić A. Composition and Potential Health Benefits of Pomegranate: A Review. Curr Pharm Des. 2019;25(16):1817-1827.

Sandoval-Acuña C, Ferreira J, Speisky H. Polyphenols and mitochondria: an update on their increasingly emerging ROS-scavenging independent actions. Arch Biochem Biophys. 2014; 559:75-90.

27- Erfidan MA, Küpeli Akkol E, Sevimli A, Civelek T. Effects of Pomegranate (Punica granatum L.) on Paracetamol Induced Acute Hepatic Damage in Mice. Kocatepe Vet J. 2016; 9(4):273-280.

Tudor M, Slencu BG, Cuciureanu R, Cuciureanu M, Filip N, Filip C. Potential protective role of selenium in experimental subacute intoxication with ethephon in rats. Farmacia. 2018;66(3):463-467.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Bio Chem. 1951;193(1):265-75.

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-8.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys, 1959;82(1):70-77.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. (Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem. 1982;126(1):131-138.

Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158-69.

De Vega L, Fernandez RP, Mateo MC, Bustamante JB, Herrero AM, Munguira EB. Glutathione determination and a study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants. Ren Fail. 2002;24(4):421-32.

Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun. 1972;46(2):849-54.

Aebi H. Catalase in vitro. Methods Enzymol. 1984; 105:121-126.

Bancroft, J.D. and M. Gamble. Theory and practice of histological techniques.Elsevier health sciences. 2008.

Stojiljkovic N, Mihailovic D, Veljkovic S, Stoiljkovic M, Jovanovic I. Glomerular basement membrane alterations induced by gentamicin administration in rats. Exp Toxicol Pathol. 2008;60(1):69-75.

Mohana Lakshmi S, UshaKiran Reddy T, Sandhya Rani KS. A review on medicinal plants for nephroprotective activity. Asian J Pharm Clin Res. 2012;5(4):8-14.

Al-Brakati AY, Kassab RB, Lokman MS, Elmahallawy EK, Amin HK, Abdel Moneim AE. Role of thymoquinone and ebselen in the prevention of sodium arsenite-induced nephrotoxicity in female rats. Hum Exp Toxicol. 2019; 38:482-493.

Khreba NA, Abdelsalam M, Wahab AM, Sanad M, Elhelaly R, Adel M, El-Kannishy G. Kidney injury molecule 1 (KIM-1) as an early predictor for acute kidney injury in post-cardiopulmonary bypass (CPB) in open heart surgery patients. Int J Nephrol. 2019: 6265307.

Cekmen M, Otunctemur A, Ozbek E, Cakir SS, Dursun M, Polat EC, Somay A, Ozbay N. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013; 35:268-274.

Abdel Moneim AE, El-Khadragy MF. The potential effects of pomegranate (Punica granatum) juice on carbon tetrachloride-induced nephrotoxicity in rats. A J Physiol Biochem Pharmacol. 2013; 69:359-370.

Khadejah Y. Al-Muwaly Khawola A. Al-Flayeh|Asmaa A. Antioxidant and free radical scavenging effects of Iraqi sumac ( Rhus coriaria L). Baghdad Sci. J. 2013;10(3):921-33.

Mahajan L, Verma PK, Raina R, Pankaj NK, Sood S, Singh M. Alteration in thiols homeostasis, protein and lipid peroxidation in renal tissue following subacute oral exposure of imidacloprid and arsenic in Wistar rats. Toxicol Rep. 2018; 5:1114-1119.

Franco JL, Posser T, Mattos JJ, Trevisan R, Brocardo PS, Rodrigues ALS, et al. Zinc reverses malathion-induced impairment in antioxidant defenses. Toxicol Lett. 2009;187(3):137-143.

Bahr, H.I., R. Hamad, and S.A. Ismail. The impact of Lactobacillus acidophilus on hepatic and colonic fibrosis induced by ethephon in a rat model. Iran J Basic Med Sci. 2019;22(8):956-962.

Ahmed MM, Zaki NI. Assessment the ameliorative effect of pomegranate and rutin on chlorpyrifos-ethyl-induced oxidative stress in rats. J Nat Sci. 2009; 7:49–61.

Khalil SR, Mohammed WA, Zaglool AW, Elhady WM, Farag MR. Inflammatory and oxidative injury is induced in cardiac and pulmonary tissue following fipronil exposure in Japanese quail: mRNA expression of the genes encoding interleukin 6, nuclear factor kappa B, and tumor necrosis factor-alpha. Environ Pollut. 2019; 251:564-572.

Lingappan, K. NF-kappaB in Oxidative Stress. Curr Opin Toxicol. 2018; 7:81-86.

Adams LS, Seeram NP, Aggarwal BB, Takada Y, Sand D, Heber D. Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells. J Agr Food Chem. 2006; 54:980-985.

Banerjee N, Kim H, Talcott S, Mertens-Talcott S. Pomegranate polyphenolics suppressed azoxymethane-induced colorectal aberrant crypt foci and inflammation. Carcinogenesis. 2013;34(12):2814-22.

Havasi, A., Borkan SC. Apoptosis and acute kidney injury. Kidney Int. 2011;80(1):29-40.

Priante G, Gianesello L, Ceol M, Del Prete D, Anglani F. Cell Death in the Kidney. Int J Mol Sci. 2019;20(14):3598.

Albrakati, A. Neuroprotective effect of physical exercise on neuronal apoptosis induced by tramadol in cerebral cortex of rats. Biointerface Res Appl Chem. 2020; 10:7209-7222.

Al-Brakati A, Albarakati AJA, Daabo HMA, Baty RS, Salem FEH, Habotta OA, et al. Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes. Metab Brain Dis. 2020; 35(7): 1175-1187.

Yesilkaya E, Bideci A, Ozer C, Elmas C, Camurdan O, Giray SG, et al. Plant growth regulator (4-chlorophenoxy acetic acid) increases apoptosis in gonads of rats without changing hormonal levels. Horm Res. 2009;72(4):225-35.

El-Okazy AM. The effects of combination of gibberellic acid-3 (ga3) and ethephon (2-chloroethyl phosphonic acid) (plant growth regulators) on some physiological parameters in mice. J Egypt Public Health Assoc. 2008;83(1-2):67-86.

Craig EA, Yan Z, Zhao QJ. The relationship between chemical-induced kidney weight increases and kidney histopathology in rats. J Appl Toxicol. 2015;35(7):729-36.

Tousson E, El-Atrsh A, Mansour M, Assem A. Histopathological and immunohistochemical studies on the effects of Ethephon on liver and kidney in male rats. Int J Biol Markers. 2019; 1:1-6.

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