Nephroprotective Effect of Luteolin Isolated from the Leaves of Saccharum officinarum L. against Gentamicin-Induced Nephrotoxicity in Wistar Rats: Biochemical, Gravimetric and Histopathological Evidence

References

[1] Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78(6):743–750.

[2] Hemalatha S. Nephrotoxicity, its mechanism and biomarkers: a systematic review. IP J Urol Nephrol Hepatol Sci. 2019;2(4):45–49.

[3] Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it?. Pharmacol Res. 2010;62(3):179–186.

[4] Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: current knowledge and future perspectives. EXCLI J. 2017;16:388–399.

[5] Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2011;79(1):33–45.

[6] Martinez-Salgado C, Lopez-Hernandez FJ, Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol. 2007;223(1):86–98.

[7] Laorodphun P, Cherngwelling R, Panya A, Arjinajarn P. Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress, endoplasmic reticulum stress and apoptosis. Pharm Biol. 2022;60(1):491–500.

[8] Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 5th ed. Oxford: Oxford University Press; 2015.

[9] Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20(7):933–956.

[10] Nabavi SF, Braidy N, Gortzi O, Sobarzo-Sanchez E, Daglia M, Skalicka-Wozniak K, Nabavi SM. Luteolin as an anti-inflammatory and neuroprotective agent: a brief review. Brain Res Bull. 2015;119:1–11.

[11] Ali SE, Yuan Q, Wang S, Farag MA. More than sweet: a phytochemical and pharmacological review of sugarcane (Saccharum officinarum L.). Food Biosci. 2021;44:101431.

[12] Singh A, Lal UR, Mukhtar HM, Singh PS, Shah G, Dhawan RK. Phytochemical profile of sugarcane and its potential health aspects. Pharmacogn Rev. 2015;9(17):45–54.

[13] Miglani I, Khanna Y, Sharma I, Kumar M, Singh R. Screening of the phytochemicals of sugarcane juice and its potential health aspects. Bio Sci Res Bull. 2023;39(1).

[14] Adjatin A, et al. Phytochemical screening and cytotoxicity of juices and bark extracts of sugarcane (Saccharum officinarum Linn) in Benin. Int J Biosci. 2019;14(5):95–105.

[15] Williams IO, Onyenweaku EO, Atangwho IJ. Nutritional and antimicrobial evaluation of Saccharum officinarum consumed in Calabar, Nigeria. Afr J Biotechnol. 2016;15(33):1789–1795.

[16] Ghiware NB, Aseemuddin N, Kawade RM, Vadvalkar SM. Pharmacological exploration of Saccharum officinarum leaf extracts for its anti-oxidant and anti-inflammatory activity. 2012.

[17] Pan X, Hao E, Xie J, Tang PL, Wen J, Du Z, et al. Mechanistic insights into the diuretic activity of sugarcane leaf extract using untargeted metabolomics and bioinformatics. Front Plant Sci. 2025;16:1652526.

[18] Singh R, Shukla R. Protective effect of Saccharum officinarum Linn juice in paracetamol-induced acute hepatotoxicity in albino rats. Asian J Pharm Res. 2021;11(1):17–22.

[19] Ziroldo JC, Torres LM, Gamberini MT. Sugarcane (Saccharum officinarum L.) induces psychostimulant, anxiolytic-like effects and improvement of motor performance in rats. J Ethnopharmacol. 2024;333:118476.

[20] Pallavi R, et al. Extraction of anthocyanin from sugarcane (Saccharum officinarum) peel and evaluation of its antioxidant and anticancer properties. 2012.

[21] Ogunwole E, Ebong JE, Audu LA. Detrimental effects of Saccharum officinarum juice on reproductive functions of female Wistar rats. Niger J Physiol Sci. 2023;38(1):107–112.

[22] Dewi IP, Aldiana M, Viadina ZA, Fajrin FA, Holidah D, Christianty FM. Nephroprotective effect of sugarcane (Saccharum officinarum L.) leaves ethanol extract on gentamicin-induced nephrotoxicity in rats. J Adv Pharm Technol Res. 2024;15(3):208–213.

[23] Imran M, Rauf A, Abu-Izneid T, Nadeem M, Shariati MA, Khan IA, et al. Luteolin, a flavonoid, as an anticancer agent: a review. Biomed Pharmacother. 2019;112:108612.

[24] Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potentials for cancer prevention and therapy. Curr Cancer Drug Targets. 2008;8(7):634–646.

[25] Domitrovic R, Cvijanovic O, Pugel EP, Zagorac GB, Mahmutefendic H, Skoda M. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology. 2013;310:115–123.

[26] Kang KP, et al. Luteolin ameliorates cisplatin-induced acute kidney injury in mice by regulation of p53-dependent renal tubular apoptosis. Nephrol Dial Transplant. 2011;26(3):814–822.

[27] Arslan BY, Arslan F, Erkalp K, Alagol A, Sevdi MS, Yildiz G, et al. Luteolin ameliorates colistin-induced nephrotoxicity in the rat models. Ren Fail. 2016;38(10):1735–1740.

[28] Tan X, et al. Dietary luteolin protects against HgCl2-induced renal injury via activation of Nrf2-mediated signaling in rat. J Inorg Biochem. 2018;179:24–31.

[29] Hong X, et al. Luteolin treatment protects against renal ischemia-reperfusion injury in rats. Mediators Inflamm. 2017;2017:9783893.

[30] Xin SB, et al. Protective effects of luteolin on lipopolysaccharide-induced acute renal injury in mice. Med Sci Monit. 2016;22:5173–5180.

[31] Wang GG, Lu XH, Li W, Zhao X, Zhang C. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med. 2011;2011:323171.

[32] Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 2020;18(7):e3000410.

[33] OECD. Test No. 420: Acute Oral Toxicity - Fixed Dose Procedure. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2002.

[34] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–358.

@article{1723901,
      author = {Neha Yadav, Prashant Kumar Singh},
      title = {Nephroprotective Effect of Luteolin Isolated from the Leaves of Saccharum officinarum L. against Gentamicin-Induced Nephrotoxicity in Wistar Rats: Biochemical, Gravimetric and Histopathological Evidence},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {4},
      pages = {1442-1454},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1723901.pdf},
      abstract = {Background: Gentamicin remains an important and inexpensive aminoglycoside antibiotic, but its clinical value is limited by dose-dependent injury to the proximal tubular epithelium, a process driven largely by oxidative stress. Sugarcane (Saccharum officinarum L.) leaves are rich in flavonoids, including luteolin, yet the contribution of luteolin to the reported renal benefits of sugarcane has not been tested directly.
Objective: To isolate luteolin from sugarcane leaves and evaluate its nephroprotective activity against gentamicin-induced nephrotoxicity in rats.
Methods: Shade-dried leaves were extracted with ethanol in a Soxhlet apparatus, and luteolin was isolated by silica-gel column chromatography with gradient elution. Identity was supported by thin-layer chromatography against authentic luteolin, melting point, and ultraviolet and infrared spectroscopy. After an acute oral toxicity study, thirty Wistar rats were divided into five groups of six: normal control, gentamicin control (80 mg/kg, i.p., 8 days), standard antioxidant, and low-dose and high-dose luteolin-rich fraction given orally with gentamicin. Serum creatinine, blood urea nitrogen (BUN), uric acid, kidney malondialdehyde (MDA), relative kidney weight, body weight and renal histology were assessed.
Results: The ethanolic extract yield was about 9–10% w/w, and the isolate showed an Rf of 0.62 against 0.61 for standard luteolin and UV maxima near 253 and 350 nm. No mortality or toxic signs occurred in the acute study. Gentamicin raised creatinine (0.72 to 3.18 mg/dL), BUN (18.4 to 62.5 mg/dL), uric acid (1.9 to 5.8 mg/dL), kidney MDA (2.1 to 7.9 nmol/mg) and relative kidney weight (0.62 to 1.05%), and caused tubular necrosis, casts and inflammation. The high dose of luteolin-rich fraction restored these values towards normal (creatinine 1.24 mg/dL, BUN 26.8 mg/dL, MDA 3.1 nmol/mg), gave about 80% protection, and preserved tubular architecture, comparable to the standard. The low dose gave intermediate protection.
Conclusions: Luteolin from sugarcane leaves protects against gentamicin nephrotoxicity in a dose-dependent manner, most probably by suppressing lipid peroxidation. Confirmation of purity by spectroscopic methods and mechanistic studies are warranted.},
      keywords = {luteolin; Saccharum officinarum; sugarcane leaves; gentamicin; nephrotoxicity; oxidative stress; malondialdehyde; nephroprotection},
      month = {October},
  }