Effect of Levo-carnosine co-administration on Cisplatin induced histomorphological changes in the liver of BALB/c mice
Article Sidebar
Main Article Content
Abstract
Objective: To study Cisplatin-induced histomorphological changes in the liver of mice and to evaluate the effects of Levo-carnosine co-administration on cisplatin induced hepatotoxicity.
Methods: This laboratory-based experimental study was conducted at Anatomy Department, Army Medical College, Rawalpindi, Pakistan, from November 2020 to April 2022. Ninety BALB/c mice were divided into three groups (n=30 each) and maintained on a standard chow diet. Group-I served as the control and received no treatment. Group-II was administered intraperitoneal cisplatin (8 mg/kg body weight) once weekly for four weeks. Group-III received the same cisplatin regimen plus daily oral Levo-carnosine (300 mg/kg body weight) via oral lavage. After four weeks, mice were euthanized, and livers were dissected, processed, and stained with Hematoxylin and Eosin to assess hepatic architecture, lobule perimeter, and central vein diameter.
Results: Disrupted lobular architecture was observed in 4 (13.7%) animals in Group-I, 25 (83.3%) in Group-II, and 14 (46.7%) in Group-III (p<0.001). Central vein diameter measured 6.89±1.01 µm in Group-I, 18.84±2.24 µm in Group II, and 9.42±1.22 µm in Group-III (p<0.001). Post hoc analysis revealed a significantly increased central vein diameter in Group-II compared to the other two groups (p<0.001). Hepatic lobule perimeter was 144.86±7.9 µm in Group-I, 121.59±6.89 µm in Group-II, and 137.01±7.84 µm in Group-III (p<0.001). Post-hoc analysis showed a significantly decreased hepatic lobule perimeter in Group-II compared to the other groups (p<0.001).
Conclusion: Cisplatin administration induced histomorphological liver changes in BALB/c mice, while Levo-carnosine co-administration attenuated these effects, preserving hepatic architecture and mitigating pathological alterations, suggesting its hepatoprotective potential.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Work published in KMUJ is licensed under a
Creative Commons Attribution 4.0 License
Authors are permitted and encouraged to post their work online
(e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
References
1. Fatima M, Zaidi SIH. Drug Induced Hepatotoxicity – An Ongoing Challenge. J Bahria Uni Med Dental Coll 2020;10(3):244-8. https://doi.org/10.51985/JBUMDC2020007
2. Van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers (Basel) 2022;14(3):627. https://doi.org/10.3390/cancers14030627
3. Ali S, Rasul A, Latif N, Aleem SB, Zia R, Khan B. Effect of Levo-Carnosine on Biomarkers of Oxidative Stress and Hepatotoxicity in Cisplatin-Treated Male Sprague Dawley Rats. Pak Armed Forces Med J 2022;72(4):1334-8. https://doi.org/10.51253/pafmj.v72i4.7815
4. Bai X, Ali A, Lv Z, Wang N, Zhao X, Hao H, et al. Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways. Eur J Med Chem 2021;224:113689. Eur J Med Chem 2021; 224:113689. https://doi.org/10.1016/j.ejmech.2021.113689
5. Kiss RC, Xia F, Acklin S. Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment. Int J Mol Sci 2021;22(15):8199. https://doi.org/10.3390/ijms22158199
6. Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 2019;12(1):7-15. https://dx.doi.org/10.13005/bpj/1608
7. Holditch SJ, Brown CN, Lombardi AM, Nguyen KN, Edelstein CL. Recent advances in models, mechanisms, biomarkers, and interventions in cisplatin-induced acute kidney injury. Int J Mol Sci 2019; 20(12):3011. https://doi.org/10.3390/ijms20123011
8. Abd Rashid N, Hussan F, Hamid A, Ridzuan NRA, Teoh S, Budin S. Preventive effects of Polygonum minus essential oil on cisplatin-induced hepatotoxicity in sprague dawley rats. Sains Malaysiana 2019;48(9):1975-88. http://dx.doi.org/10.17576/jsm-2019-4809-19
9. Kowaltowski AJ, de Souza-Pinto NC, Castilho RF, Vercesi AE. Mitochondria and reactive oxygen species. Free Radic Biol Med 2009;47(4):333-43. https://doi.org/10.1016/j.freeradbiomed.2009.05.004
10. Boldyrev A. Carnosine: new concept for the function of an old molecule. Biochemistry (Mosc) 2012;77(4):313-26. https://doi.org/10.1134/s0006297912040013
11. Nelson MM, Builta ZJ, Monroe TB, Doorn JA, Anderson EJ. Biochemical characterization of the catecholaldehyde reactivity of L-carnosine and its therapeutic potential in human myocardium. Amino Acids 2019; 51(1):97-102. https://doi.org/10.1007/s00726-018-2647-y
12. Sharp CN, Doll MA, Dupre TV, Shah PP, Subathra M, Siow D, et al. Repeated administration of low-dose cisplatin in mice induces fibrosis. Am J Physiol Renal Physiol 2016;310(6):F560-8. https://doi.org/10.1152/ajprenal.00512.2015
13. Abplanalp W, Haberzettl P, Bhatnagar A, Conklin DJ, O'Toole TE. Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice. J Am Heart Assoc 2019;8(13):e013041. https://doi.org/10.1161/jaha.119.013041
14. Abbas G, Shah S, Hanif M, Asghar A, Shafique M, Ashraf K. Cancer prevalence, incidence and mortality rates in Pakistan in 2018. Bull Cancer 2020;107(4):517-8. https://doi.org/10.1016/j.bulcan.2019.12.011
15. Ijaz MU, Aziz S, Faheem M, Abbas K, Nasir S, Naz H, et al. Orientin Attenuates Cisplatin-Induced Renal Toxicity by Reducing Oxidative Stress and Inflammation. Pak Vet J 2021;41(4):574-8. http://dx.doi.org/10.29261/pakvetj/2021.076
16. Sioud F, Ben Toumia I, Lahmer A, Khlifi R, Dhaouefi Z, Maatouk M, et al. Methanolic extract of Ephedra alata ameliorates cisplatin-induced nephrotoxicity and hepatotoxicity through reducing oxidative stress and genotoxicity. Environ Sci Pollut Res Int 2020;27(11):12792-801. https://doi.org/10.1007/s11356-020-07904-3
17. Abdel-Daim MM, Abdel-Rahman HG, Dessouki AA, Ali H, Khodeer DM, Bin-Jumah M, et al. Impact of garlic (Allium sativum) oil on cisplatin-induced hepatorenal biochemical and histopathological alterations in rats. Sci Total Environ 2020;710:136338. https://doi.org/10.1016/j.scitotenv.2019.136338
18. Habib SA, Abdelrahman RS, Abdel Rahim M, Suddek GM. Anti‐apoptotic effect of vinpocetine on cisplatin‐induced hepatotoxicity in mice: The role of Annexin‐V, Caspase‐3, and Bax. J Biochem Mol Toxicol 2020;34(10):e22555. https://doi.org/10.1002/jbt.22555
19. Ghanbarinejad V, Ahmadi A, Niknahad H, Ommati MM, Heidari R. Carnosine mitigates manganese mitotoxicity in an in vitro model of isolated brain mitochondria. Adv Pharm Bull 2019;9(2):294-301. https://doi.org/10.15171/apb.2019.034
20. Almansory AH, Al-Shaibani EA, Shediwah FM, Ibrahim HM. The Effect of Cisplatin and 5-Fluorouracil versus Aloe perryi extracts on Rat Liver and Kidney Tissues. PSM Vet Res 2021;6(3):59-73.
21. El-Shafai NM, Farrag F, Shukry M, Mehany H, Aboelmaati M, Abu-Ali O, et al. Effect of a Novel Hybrid Nanocomposite of Cisplatin–Chitosan on Induced Tissue Injury as a Suggested Drug by Reducing Cisplatin Side Effects. Biol Trace Elem Res 2022;200(9):4017-26. https://doi.org/10.1007/s12011-021-02994-7
22. Soliman MM, Aldhahrani A, Metwally MM. Hepatoprotective effect of Thymus vulgaris extract on sodium nitrite-induced changes in oxidative stress, antioxidant and inflammatory marker expression. Sci Rep 2021;11(1):5747. https://doi.org/10.1038/s41598-021-85264-9
23. Khedr LH, Rahmo RM, Farag DB, Schaalan MF, Hekmat M. Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29. Food Chem Toxicol 2020;140:111307. https://doi.org/10.1016/j.fct.2020.111307
24. Menon K, Cameron JD, de Courten M, de Courten B. Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial. BMJ Open 2021;11(5):e043680. https://doi.org/10.1136/bmjopen-2020-043680