Histological and Biochemical Evaluation of Rat Liver and Kidney Following Nitrofurantoin Administration

Subject Areas : Journal of Chemical Health Risks

Omewomano Peace Onyilo ¹ (Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria)
Efe Endurance Ahama ² (Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria)
Oghenenyerhovwo Success Okorodudu ³ (Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria)
Ehizokhale Santos Ehebha ⁴ (Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria)
Chikodili Judith Okoro ⁵ (Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria)

Received: 2024-01-25 Accepted : 2024-07-07 Published : 2024-08-20

Keywords: Nitrofurantoin, Liver, Kidney, Rat,

Abstract :

Nitrofurantoin (NFR) is an antibiotic commonly used in the management of uncomplicated urinary tract infections. The study examined histoarchitectural and biochemical alterations in the liver and kidney of Wistar rats following exposure to nitrofurantoin. Fifteen (15) adult Wistar rats comprising five (5) animals per group were randomly assigned into three groups. Group A was the control group while Groups B and C received 30mg kg-1 and 60mg kg-1 body weight of NFR respectively for thirty (30) days. Data generated from liver and renal functional markers was analyzed on graph pad prism using descriptive statistics and outcomes implicated as standard error of the mean and mean. Mean value differences were evaluated using analysis of variance (ANOVA) considering p<0.05 as statistically significant value. Upshot display periportal hepatitis in the group given 30mg kg-1 of nitrofurantoin, the hepatocytes appeared polygonal and there was vascular congestion with inflammatory cell infiltration in rats given 60mg kg-1 NFR. These features were consistent with inflammatory responses. However, liver function tests showed a significant increase in Alanine transaminase (ALT), Aspartate aminotransferase (AST), and Alkaline phosphatase (ALP) levels across treated groups when rationalized to control group (p<0.05). Also observed is a statistically significant increase in mean serum level of total protein, direct and indirect Bilirubin across treatment groups compared to control. More so, there were features consistent with normal renal histoarchitecture with tubules comprising of multiple segments and corpuscle made up of the Glomerulus surrounded by the podocytes. Conversely, renal function parameters showed a decrease in the urea level across treatment groups. Nitrofurantoin displays no histoarchitectural outcome of the kidney but elucidated negative outcome on the liver histology, therefore caution should be considered when administered as a therapeutic agent.

References:

1. Ortega Martell J.A., Naber K.G., Milhem Haddad J., 2019. Prevention of recurrent urinary tract infections: bridging the gap between clinical practice and guidelines in Latin America. Ther Adv Urol. 11, 1756287218824089.
2. Huttner A., Verhaegh E.M., Harbarth S., 2015. Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials. J Antimicrob Chemother. 70, 2456 - 2464.
3. Luk T., Edwards B.D., Bates D., Evernden C., Edwards J., 2021.Nitrofurantoin-induced liver failure: a fatal yet forgotten complication. Can Fam Phy. 67, 342- 344
4. Wonnacott S., Gala D., Shah M., Kaul D., Kumar V., 2022. An Unusual Case of Drug-Induced Liver Injury Secondary to Nitrofurantoin Use. Cureus. 14(7), e26882. Doi: 10.7759/cureus.26882
5. Abaas N.F., Haba M.K., 2015. Histopathological changes caused by the chronic effect of nitrofurantoin drug in the testes of albino mice. Bagh Sci J. 12(1), 20 - 26.
6. Appleyard S., Saraswati R., Gorard D.A., 2010. Autoimmune hepatitis triggered by nitrofurantoin: a case series. J Med Cas Rep. 4, 1 - 5.
7. Rizk A., 2011. Effect of Nitrofurantoin on the Lungs of Adult Albino Rat and the Possible Protective Role of Vitamin E. https:// scholar.cu. edu.eg/? q=aymanrizk/ publications/effect-nitrofurantoin-lungs-adult-albino-rat-and-possible-protective-role-vit.
8. Chalasani N., Bonkovsky H.L., Fontana R., 2015. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroentero. 148, 1340-1352.e7
9. Muller A.E., Verhaegh E.M., Harbarth S., 2017. Nitrofurantoin’s efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials. Clin Microbiol Infec. 23, 355 - 362
10. de Boer Y.S., Kosinski A.S., Urban T.J., 2017. Features of autoimmune hepatitis in patients with drug-induced liver injury. Clin Gastroenterol Hepatol. 15, 103-112.e2.https:// doi.org/ 10. 1016/j. cgh. 2016. 05. 043.
11. Bjornsson E.S., 2017. Drug-induced liver injury due to antibiotics. Scand.JGastroenterol. 52, 617 - 623.
12. Bessone F., Ferrari A., Hernandez N., Mendizabal M., Ridruejo E., Zerega A., Tanno F., Reggiardo M.V., Vorobioff J., Tanno H., Arrese M., Nunes V., Tagle M., Medina Caliz I., Robles Diaz M., Niu H., AlvarezAlvarez I., Stephens C., Lucena M.I., Andrade R.J., 2023. Nitrofurantoin induced liver injury: long term follow up in two prospective DILI registries.Arch Toxicol. 97, 593 - 602
13. Naidoo S., Meyers A.M., 2015. Drug and Kidney.SoutAfr Med J. 105(4), 322.
14. Namagondlu G., Low S.E.,Seneviratne R., Banerjee A., 2010. Acute renal failure from nitrofurantoin-induced acute granulomatous interstitial nephritis.QJM: Int J M.103(1), 49 - 52.
15. Ahama E.E., Igben V.O., Ubogu J., Osakue I.I., Nwabuoku U.S., Okwuribo P., Kpangban A., Odokuma E.I., 2023. Potential Nephrotoxic Sequel of the Kidney Following Exposure to Turmeric Extract in Adult Wistar Rats. J Col Med Sci Nep. 19(4), 482 - 488; DOI:10.3126/jcmsn.v19i4.48718
16. Ahama E.E., Odokuma E.I., 2023. Histomorphological Effects of Oral Nicotine administration on the testes of adult wistar rats. Journal of Chemical Health Risks. 13(2), 291 - 298. DOI: 10,22034/ jchr.2022.1949064.1488
17. Ahama E.E., Odokuma E.I., Ehebha E.S., Enakpoya O.P., 2024. Histological Sequel Following Exposure to Levonorgestrel on Wistar Rat Ovary. Journal of Chemical Health Risks. 14(1), 71-86.
18. Callaghna E., 2020. Bilirubin.Retrieved from: https://www.randox.com/tag/liver-function-tests/ (accessed 14 August, 2022).
19. Mack C.L., Adams D., Assis D.N., 2020. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases. Hepatol. 72, 671 – 722.
20. McCracken D., 2015. Nitrofurantoin Induced Liver Injury. JSM Gastroenterol Hepatol. 3(1), 1040.