Ameliorative Effect of Eruca sativa Seeds and Its Rutin on Gentamicin‑Induced Nephrotoxicity in Male Rats via Targeting Inflammatory Status, Oxidative Stress and Kidney Injury Molecule-1 (KIM-1)/Cystatin C Expression

Reda Salah-Eldin Abdelkader, Nadia Mohamed El-Beih, Samir Attia Zaahkouk, Enas Ali El-Hussieny

Abstract


BACKGROUND: Nephrotoxicity of Gentamicin (GM), an important aminoglycoside, is still a serious issue in clinical use. Therefore, natural products are currently being used as an alternate source of medicinal substances by researchers all over the world for new medication molecules. Eruca sativa shows several health benefits that appear to be associated with the content of flavonoids. Therefore, the objective of the present study was to evaluate the effect of  E. sativa seed extract (ESE) and its active flavenol rutin (RUT) in GM-induced nephrotoxicity in adult male rats. 

METHODS: The animals were divided into 10 groups: a control group, a groups administered 150 mg/kg body weight (BW) of ESE, a group administered 300 mg/kg BW of ESE, a group administered with 50 mg/kg BW of RUT, a group administered with 100 mg/kg BW of RUT, a GM-nephrotoxic group, and four GM-nephrotoxic groups treated with the same doses of ESE and RUT as previous groups. The treatments were given orally for 4 weeks. Following the treatments animals in all groups were sacrificed. The blood samples were drawn, and the kidney tissue samples were collected for further analysis.

RESULTS: ESE alleviated the nephrotoxic effects of GM as it decreased the serum levels of creatinine, urea, Na+, K+, tumor necrosis factor-α (TNF- α), and interleukin-1β (IL-1β). Moreover, ESE was linked with kidney injury molecule-1 (KIM-1) and Cystatin C mRNA downregulation. Although treatment with pure RUT induced the same modulation of ESE in GM- nephrotoxic rats, pure RUT was more effective than ESE in the modulation of oxidative kidney injury.

CONCLUSION: The present study revealed the health-promoting effects of ESE or RUT in the attenuation of GM-induced nephrotoxicity.

KEYWORDS: nephrotoxicity, gentamicin, Eruca sativa, rutin, inflammation, KIM-1/cystatin C expression


Full Text:

PDF

References


Maldonado PD, Barrera D, Rivero I, Mata R, Medina-Campos ON, Hernández-Pando R, et al. Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage. Free Radical Biol Med. 2003; 35(3): 317–24, CrossRef.

Safa J, Argani H, Bastani B, Nezami N, Ardebili BR, Ghorbanihaghjo A, et al. Protective effect of grape seed extract on gentamicin-induced acute kidney injury. Iran J Kid Dis. 2010; 4(4): 285–91, PMID.

Kandemir FM, Ozkaraca M, Yildirim BA, Hanedan B, Kirbas A, Kilic K, et al. Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats. Ren Fail. 2015; 37(3): 518–25, CrossRef.

Quiros Y, Vicente-Vicente L, Morales AI, Lopez-Novoa J, Lopez-Hernandez FJ. An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci. 2011; 119(2): 245–56, CrossRef.

Endre Z, Pickering J, Walker R, Devarajan P, Edelstein C, Bonventre J, et al. Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int. 2012; 79(10): 1119–30, CrossRef.

Ali SS, Rizvi SZ, Muzaffar S, Ahmad A, Ali A, Hassan SH. Renal cortical necrosis: a case series of nine patients & review of literature. J Ayub Med Coll. 2003; 15(2): 41–4, PMID.

Cekmen M, Otunctemur A, Ozbek E, Cakir S, Dursun M, Polat E, et al. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013; 35(2): 268–74, CrossRef.

Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacok Inet. 2004; 19(3): 159–70, CrossRef.

Abdul-jabbar RS. Polyphenol and flavonoid contents and antioxidant activity in freshly consumed rocket (Eruca sativa). Mat Sci Eng. 2018; 454(1): 012158, CrossRef.

Jaafar NS, Jaafar IS. Eruca sativa lining: pharmacognostical and pharmacological properties and pharmaceutical preparation. Asian J Pharm Clin Res. 2019; 12: 39–45, CrossRef.

Sarwar AM, Kaur G, Jabbar Z, Javed K, Athar M. Eruca sativa seeds possess antioxidant activity and exert a protective effect on mercuric chloride-induced renal toxicity. Food Chem Toxicol. 2007; 45(6): 910–20, CrossRef.

Perron N, Brumaghim J. A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys. 2009; 53(2): 75–100, CrossRef.

Andersen OM, Markham KR, ed. Flavonoids: Chemistry, Biochemistry and Applications. New York: Taylor and Francis Group; 2006, NLMID.

Villatoro-Pulido M, Priego-Capote F, A´lvarez-Sa´nchez B, Saha S, Philo M, Obrego´n-Cano S, et al. An approach to the phytochemical profiling of rocket [Eruca sativa (Mill.) Thell]. J Sci Food Agric. 2013; 93(15): 3809–19, CrossRef.

Sharma S, Asgar A, Javed A, Jasjeet KS, Sanjula B. Rutin: therapeutic potential and recent advances in drug delivery. Expert Opin Investig Drugs. 2013; 22(8): 1063–79, CrossRef.

Korkmaz A, Kolankaya D. Protective effect of rutin on the ischemia/reperfusion induced damage in rat kidney. J Surg Res. 2010; 164(2): 309–15, CrossRef.

Javed H, Khan MM, Ahmad A, Vaibhav K, Ahmad ME, Khan A, et al. Rutin prevents cognitive impairments by ameliorating oxidative stress and neuroinflammation in rat model of sporadic dementia of Alzheimer type. Neuroscience. 2012; 210: 340–52, CrossRef.

Stanley Mainzen Prince P, Kamalakkannan N. Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. J Biochem Mol Toxicol. 2006; 20(2): 96–102, CrossRef.

Shalaby MA, Hammouda AA. Nephroprotective, diuretic and antioxidant effects of some medicinal herbs in gentamicin-nephrotoxic rats. J Intercult Ethnopharmacol. 2014; 3(1): 1–8, CrossRef.

Kim KH, Tsao R, Yang R, Cui SW. Phenolic acid profiles and antioxidant activities of wheat bran extracts and the effect of hydrolysis conditions. Food Chem. 2006; 95(3): 466–73, CrossRef.

Bibu KJ, Joy AD, Mercey KA. Therapeutic effect of ethanolic extract of Hygrophila spinosa T. Anders on Gentamicin- induced nephrotoxicity in rats. Indian J Exp Biol. 2010; 48(9): 911–7, PMID.

Karahan I, Atessahin A, Yılmaz S, Ceribas AO, Sakin F. Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicology. 2005; 215(3): 198–204, CrossRef.

Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Di Paola R, Britti D. A role for superoxide in gentamicin-mediated nephropathy in rats. Eur. J Pharmacol. 2002; 450(1): 67–76, CrossRef.

Atessahin A, Karahan I, Yilmaz S, Ceribasi AO, Princci I. The effect of manganese chloride on gentamicine-induced nephrotoxicity in rats. Pharmacol Res. 2003; 48(6): 637–42, CrossRef.

Nakajima T, Hishida A, Kato A. Mechanisms for protective effects of free radical scavengers on gentamicin-mediated nephropathy in rats. Am J Physiol. 1994; 266(3): 425–31, CrossRef.

Elgazar AF, Abo Raya AO. Nephroprotective and diuretic effects of three medicinal herbs against gentamicin-induced nephrotoxicity in male rats. Pak J Nut. 2013; 12(8): 715–22, CrossRef.

Chen SS, Gong J, Liu FT, Mohammed U. Naturally occurring polyphenolic antioxidants modulate IgE mediated mast cell activation. Immunology. 2000; 100(4): 471–80, CrossRef.

Vellosa JR, Regasini LO, Khalil NM, Silva V, Khalil OAK, Manente MM, et al. Antioxidant and cytotoxic studies for kaempferol, quercetin and isoquercitrin. Ecl Quím São Paulo. 2011; 36: 7–20, CrossRef.

Bajilan SI, Al-naqeeb AA. Effect of the aqueous extract of rocket (Eruca sativa L.) leaves on the histological structure of some organs in male mice. Journal of the college of basic education. 2011; 17: 13–21, article.

Zhang Z, naughton DP, Blake DR, Beniamin N, Winyard PG, et al. Human xanthine oxidase converts nitrite ions into nitric oxide (NO). Biochem Soc Trans. 1997; 25 (3): 524S, CrossRef.

Kayama F, Yoshida T, Kodama Y, Matsui T, Matheson JM, Luster M I. Pro‐inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin. Cytokine. 1997; 9(9): 688–95, CrossRef.

Qu S, Dai C, Lang F, Hu L, Tang Q, Wang H, et al. Rutin attenuates vancomycin-induced nephrotoxicity by ameliorating oxidative stress, apoptosis, and inflammation in rats. Antimicrob Agents Chemo. 2019; 63(1): 1545–18, CrossRef.

Okura T, Jotoku M, Irita J, Enomoto D, Nagao T, Desilva VR, et al. Association between Cystatin C and inflammation in patients with essential hypertension. Clin Exp Nephrol. 2010; 14(6): 584–8, CrossRef.

Wang Y, Feng F, Liu M, Xue J, Huang H. Resveratrol ameliorates sepsis‑induced acute kidney injury in a pediatric rat model via Nrf2 signaling pathway. Exp ther med. 2018; 16(4): 3233–3240, CrossRef.

Khandrika L, Koul S, Meachaml RB, Koul HK. Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo. PLoS one. 2012; 7(9): 44174. https://doi.org/10.1371/journal.pone.0044174">CrossRef.

Spanu S, van Roeyen CRC, Denecke B, Floege J, Mu¨ hlfeld AS. Urinary Exosomes: a novel means to non-invasively assess changes in renal gene and protein expression. PLoS one. 2014; 9(10): 109631, CrossRef.

Christian FT, Katharina F, Barbara E. Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials. Toxicol Pathol. 2012; 40(7): 1031–48, CrossRef.

Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A and Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008; 52(3): 595–605, CrossRef.

Ohse T, Vaughan MR, Kopp JB, Krofft RD, Marshall CB, Chang AM, et al. De novo expression of podocyte proteins in parietal epithelial cells during experimental glomerular disease. Am J Physiol Renal Physiol. 2010; 298(3): 702–11, CrossRef.

Stojanović VD, Vučković NM, Barišić NA, Srdić B, Doronjski AD, Peco Antić AE. Early biomarkers of renal injury and protective effect of erythropoietin on kidneys of asphyxiated newborn rats. Pediatr Res. 2014; 76(1): 11–6, CrossRef.




DOI: https://doi.org/10.18585/inabj.v14i1.1766

Indexed by:

                 

                

                 

 

The Prodia Education and Research Institute