Evaluation of Biochemical and Pathological Parameters at Different Doses of Cisplatin in Experimental Animal Model: Toxicological Study on an Antineoplastic Drug

Farhana Sultana, Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka 1229, BangladeshFollow
Muhammed Mohibul Islam, Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3815, BangladeshFollow
Mohammad Nurul Amin, Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka 1229, BangladeshFollow
Nusrat Jahan, Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3815, BangladeshFollow
Asma Kabir, Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka 1229, BangladeshFollow
Talha Bin Emran, Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, BangladeshFollow
Bibek Chandra Sutradhar, Department of Medicine and Surgery, Chittagong Veterinary and Animal Science University, Chittagong 4225, BangladeshFollow
Sujan Banik, Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3815, BangladeshFollow

ORCID ID

Farhana Sultana : 0000-0003-3882-2555

Muhammed Mohibul Islam : 0000-0002-3605-8867

Mohammad Nurul Amin : 0000-0002-8296-3542

Nusrat Jahan : 0000-0002-9070-5105

Asma Kabir : 0000-0002-9394-6406

Talha Bin Emran : 0000-0003-3188-2272

Bibek Chandra Sutradhar : 0000-0003-0045-5788

Sujan Banik : 0000-0001-9639-6836

Abstract

Background: This study aimed to assess the effect of cisplatin-induced toxicities on biochemical and pathological parameters such as body, liver, and kidney weights, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and blood cells (RBCs and WBCs) in white Swiss albino mice.

Methods: Cisplatin’s potential toxic effects on body, liver, and kidney weights were evaluated using standard laboratory methods. Blood biochemical levels such as BUN, creatinine, and ALT levels were determined by an auto-hemolyzer using commercial diagnostic kits. Blood cells (RBCs and WBCs) were counted under a microscope by a hemocytometer.

Results: Cisplatin’s potential toxic effects on body, liver, and kidney weights were evaluated using standard laboratory methods. Blood biochemical levels such as BUN, creatinine, and ALT levels were determined by an auto-hemolyzer using commercial diagnostic kits. Blood cells (RBCs and WBCs) were counted under a microscope by a hemocytometer.

Conclusions: This study suggested to increase caution when using cisplatin, particularly at high doses. Further investigation shall be performed to minimize its toxic effect and optimize its use.

References

Pandir D, Kara Ö. Cisplatin-induced kidney damage and the protective effect of bilberry (Vaccinium myrtillus L.): An experimental study. Turk J Med Sci. 2013;43:951–6.
Mashhadi MA, Arab MR, Azizi F, Shahraki MR. Histological study of toxic effects of cisplatin single dose injection on rat kidney. Gene Cell Tissue. 2014;1:e21536.
Ali BH, Ramkumar A, Madanagopal TT, Waly MI, Tageldin M, Al-abri S, et al. Motor and behavioral changes in mice with cisplatin induced acute renal failure. Physiol Res. 2014;63:35–45.
Li S, Nagothu K, Ranganathan G, Ali SM, Shank B, Gokden N, et al. Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin mediated acute kidney injury. Am J Physiol Renal Physiol. 2012;303:F437–48.
Aleksunes LM, Goedken MJ, Rockwell CE, Thomale J, Manautou JE, CKlaassen CD. Transcriptional regulation of renal cytoprotective genes by Nrf2 and its potential use as a therapeutic target to mitigate cisplatin-induced nephrotoxicity. J Pharmacol Exp Ther. 2010;335:2–12.
Man Q, Deng Y, Li P, Ma J, Yang Z, Yang X, et al. Licorice ameliorates cisplatin-induced hepatotoxicity through antiapoptosis, antioxidative stress, anti-inflammation, and acceleration of metabolism. Front Pharmacol. 2020;11:563750.
Borchert S, Suckrau P, Walter R, Wessolly M, Mairinger E, Steinborn J, et al. Impact of metallothionein-knockdown on cisplatin resistance in malignant pleural mesothelioma. Sci Rep. 2020;10:18677.
Duan Y, Duan J, Feng Y, Huang X, Fan W, Wang K, et al. Hepatoprotective activity of vitamin e and metallothionein in cadmium-induced liver injury in ctenopharyngodon idellus. Oxid Med Cell Longev. 2018;2018:12
Darvesh A, Bishayee A. Selenium in the prevention and treatment of hepatocellular carcinoma. Anticancer Agents Med Chem. 2010;10:338–45.
Meng Z, Wang L, Liao Y, Peng Z, Li D, Zhou X, et al. The protective effect of heme oxygenase-1 on liver injury caused by don-induced oxidative stress and cytotoxicity. Toxins. 2021;13:732.
Gong C, Qian L, Yang H, Ji L, Wei H, Zhou W, et al. Hepatotoxicity and pharmacokinetics of cisplatin in combination therapy with a traditional Chinese medicine compound of Zengmian Yiliu granules in ICR mice and SKOV-3-bearing nude mice. BMC Complement Altern Med. 2015;15:283.
Bryer E, Henry D. Chemotherapy-induced anemia: Etiology, pathophysiology, and implications for contemporary practice. Int J Clin Transfus Med. 2018;6:21–31.
Family L, Xu L, Xu H, Cannavale K, Sattayapiwat O, Page J, et al. The effect of chemotherapy-induced anemia on dose reduction and dose delay. Support Care Cancer. 2016;24:4263–71.
Lang E, Lang F. Triggers, inhibitors, mechanisms, and significance of eryptosis: The suicidal erythrocyte death. Biomed Res Int. 2015;2015:1–16.
Pan H, Shen K, Wang X, Meng H, Wang C, Jin B. protective effect of metalloporphyrins against cisplatin-induced kidney injury in mice. PLoS One. 2014;9:e86057.
Chung J, Ou X, Kulkarni R, Yang C. Counting white blood cells from a blood smear using fourier ptychographic microscopy. PLoS One. 2015;10:e0133489.
Mitazaki S, Hashimoto M, Matsuhashi Y, Honma S, Suto M, Kato N, et al. Interleukin-6 modulates oxidative stress produced during the development of cisplatin nephrotoxicity. Life Sci. 2013;92:694–700.
Pezeshki Z, Khosravi A, Nekuei M, Khoshnood S, Zandi E, Eslamian M, et al. Time course of cisplatin-induced nephrotoxicity and hepatotoxicity. J Nephropathol. 2017;6:163–7.
Garcia J, Scherer T, Chen J, Guillory B, Nassif A, Papusha V, et al. Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice. Endocrinology. 2013;154: 3118–29.
Yakabi K, Sadakane C, Noguchi M, Ohno S, Ro S, Chinen K, et al. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia. Endocrinology. 2010;151:3773–82.
Ito M, Kato K, Yamamoto S, Imazeki H, Aoki M, Oshima K, et al. Loss of body weight during neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil as predictive of poor survival of patients with esophageal squamous cell carcinoma. J Clin Oncol. 2020;38:371.
Li P, Burdmann E, Mehta R. Acute kidney injury: Global health alert. Kidney Int. 2013;83:372–6.
Palipoch S, Punsawad C. Biochemical and histological study of rat liver and kidney injury induced by cisplatin. J Toxicol Pathol. 2013;26:293–9.
Volarevic V, Djokovic B, Jankovic M, Harrell C, Fellabaum C, Djonov V et al. Molecular mechanisms of cisplatin-induced nephrotoxicity: A balance on the knife edge between renoprotection and tumor toxicity. J Biomed Sci. 2019;26:25.
Ozkok A, Edelstein C. Pathophysiology of cisplatin-induced acute kidney injury. BioMed Res Int. 2014;2014:17.
Yarijania Z, Godinia A, Madanib S, Najafia H. Reduction of cisplatin-induced renal and hepatic side effects in rat through antioxidative and anti-inflammatory properties of Malva sylvestris L. extract. Biomed Pharmacother. 2018;106:1767–74.
Liu Y, Webb HK, Fukushima H, Micheli J, Markova S, Olson JL, et al. Attenuation of cisplatin-induced renal injury by inhibition of soluble epoxide hydrolase involves nuclear factor κB signaling. J Pharmacol Exp Ther. 2012;341:725–34.
Marković SD, Djačić DS, Cvetković DM, Obradović AD, Žižić JB, Ognjanović BI, et al. Effects of acute in vivo cisplatin and selenium treatment on hematological and oxidative stress parameters in red blood cells of rats. Biol Trace Elem Res. 2011;142:660–70.
Forbes CA, Worthy G, Harker J, Kleijnen J, Kutikova L, Zelek L, et al. Dose efficiency of erythropoiesis-stimulating agents for the treatment of patients with chemotherapy-induced anemia: a systematic review. Clin Ther. 2014;36:594–610.
Gilreath JA, Stenehjem DD, Rodgers GM. Diagnosis and treatment of cancer-related anemia. Am J Hematol. 2014;89:203–212.
Radziwon P, Krzakowski M, Kalinka-Warzocha E. Anemia in cancer patients-expert group recommendations. Oncol Clin Pract. 2017;13:202–10.
Pabla N, Dong Z. Curtailing side effects in chemotherapy: A tale of PKCdelta in cisplatin treatment. Oncotarget. 2012;3:107–11.

Recommended Citation

Sultana F, Islam M, Amin M, Jahan N, Kabir A, Emran T, et al. Evaluation of Biochemical and Pathological Parameters at Different Doses of Cisplatin in Experimental Animal Model: Toxicological Study on an Antineoplastic Drug. Makara J Health Res. 2022;26.