Longitudinal Evaluation of Developmental Protein Malnutrition Resembling Marasmic-Kwashiorkor Condition in Wistar Rats

Overview

Journal Turk J Pharm Sci

Specialty Pharmacology

Date 2024 Nov 21

PMID 39569711

Authors

Varsha Augustin

Murali Badanthadka

Madhura R J

Vinitha Dsouza

B Mohana Kumar

A Veena Shetty

Affiliations

Soon will be listed here.

Abstract

Objectives: Protein malnutrition (PMN) is a significant public health concern that can aggravate pathological states. The impact of early malnutrition on metabolism needs extensive evaluation. Current models employ short-term diet restriction and are neither ethically correct nor clinically relevant. This study aimed to develop a PMN rat model to evaluate the effects of a low-protein diet (LPD) on physiological, hematological, biochemical, and histological changes affected by malnourishment from postweaning to the 40 week.

Materials And Methods: The PMN model was developed in Wistar rats (post-weaning) by assigning animals to patented LPD (10% protein) and a control group to a normal diet (18% protein). Developed model was confirmed by biometric, biochemcial parameters and Gomez classification of malnutrition.

Results: LPD-induced PMN showed stunted growth, altered biochemical (albumin range, 1.9 - 2.4 g/dL, total protein range, 5.1 - 6.4 g/dL), and hematological markers mean corpuscular volume (52.03 ± 1.34, 47.45 ± 0.44, p≤0.01), mean corpuscular hemoglobin (17.67 ± 0.47, 15.37 ± 0.18, p≤0.001) and mean corpuscular haemoglobin concentration (33.87 ± 0.22, 32.37 ± 0.24, p≤0.001) and significantly affected hepatic histology. A long-term study was conducted to analyze the pattern of developmental PMN and its stabilization over time.

Conclusion: The developed PMN rat model imitates clinical conditions and is confirmed as a stable, reproducible, and reliable model for short- and long-term studies. The clinical relevance of this approach opens new avenues for research in treatment, drug development, molecular interactions, and disease model development.

References

BAINTON D, Finch C . THE DIAGNOSIS OF IRON DEFICIENCY ANEMIA. Am J Med. 1964; 37:62-70. DOI: 10.1016/0002-9343(64)90212-8. View

Malta A, de Oliveira J, da Silva Ribeiro T, Tofolo L, Barella L, Prates K . Low-protein diet in adult male rats has long-term effects on metabolism. J Endocrinol. 2014; 221(2):285-95. DOI: 10.1530/JOE-13-0473. View

Rothschild M, ORATZ M, SCHREIBER S . Effects of nutrition and alcohol on albumin synthesis. Alcohol Clin Exp Res. 1983; 7(1):28-30. DOI: 10.1111/j.1530-0277.1983.tb05406.x. View

Hoffer L . Clinical nutrition: 1. Protein-energy malnutrition in the inpatient. CMAJ. 2002; 165(10):1345-9. PMC: 81630. View

Minana-Solis M, Escobar C . Post-weaning protein malnutrition in the rat produces short and long term metabolic impairment, in contrast to earlier and later periods. Int J Biol Sci. 2008; 4(6):422-32. PMC: 2586678. DOI: 10.7150/ijbs.4.422. View

Nandivada P, Potemkin A, Carlson S, Chang M, Cowan E, OLoughlin A . Elevated Alkaline Phosphatase in Infants With Parenteral Nutrition-Associated Liver Disease Reflects Bone Rather Than Liver Disease. JPEN J Parenter Enteral Nutr. 2014; 39(8):973-6. DOI: 10.1177/0148607114545995. View

Oshikoya K, Senbanjo I . Pathophysiological changes that affect drug disposition in protein-energy malnourished children. Nutr Metab (Lond). 2009; 6:50. PMC: 2794862. DOI: 10.1186/1743-7075-6-50. View

Soeters P, Wolfe R, Shenkin A . Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2018; 43(2):181-193. PMC: 7379941. DOI: 10.1002/jpen.1451. View

Getawa S, Getaneh Z, Melku M . Hematological Abnormalities and Associated Factors Among Undernourished Under-Five Children Attending University of Gondar Specialized Referral Hospital, Northwest Ethiopia. J Blood Med. 2020; 11:465-478. PMC: 7755328. DOI: 10.2147/JBM.S284572. View

10.

Weltman M, Farrell G, Liddle C . Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology. 1996; 111(6):1645-53. DOI: 10.1016/s0016-5085(96)70028-8. View

11.

Li N, Zhou H, Tang Q . Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases. Dis Markers. 2017; 2017:7089493. PMC: 5606102. DOI: 10.1155/2017/7089493. View

12.

R J M, A V, Chakraborthy A, B M, Shetty A V, Badanthadka M . Protein malnutrition in BALB/C mice: A model mimicking clinical scenario of marasmic-kwashiorkor malnutrition. J Pharmacol Toxicol Methods. 2022; 119:107231. DOI: 10.1016/j.vascn.2022.107231. View

13.

Doherty J, Adam E, Griffin G, Golden M . Ultrasonographic assessment of the extent of hepatic steatosis in severe malnutrition. Arch Dis Child. 1992; 67(11):1348-52. PMC: 1793750. DOI: 10.1136/adc.67.11.1348. View

14.

Eyzaguirre-Velasquez J, Olavarria-Ramirez L, Gonzalez-Arancibia C, Diaz-Merino C, Ariz R, Lopez S . Protein Malnutrition During Juvenile Age Increases Ileal and Colonic Permeability in Rats. J Pediatr Gastroenterol Nutr. 2016; 64(5):707-712. DOI: 10.1097/MPG.0000000000001324. View

15.

Freiman I, Pettifor J, Moodley G . Serum phosphorus in protein energy malnutrition. J Pediatr Gastroenterol Nutr. 1982; 1(4):547-50. DOI: 10.1097/00005176-198212000-00016. View

16.

Pereira S, Baker S . Hematologic studies in Kwashiorkor. Am J Clin Nutr. 1966; 18(6):413-20. DOI: 10.1093/ajcn/18.6.413. View

17.

Fukumoto S, Ozono K, Michigami T, Minagawa M, Okazaki R, Sugimoto T . Pathogenesis and diagnostic criteria for rickets and osteomalacia - proposal by an expert panel supported by Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society. Endocr J. 2015; 62(8):665-71. DOI: 10.1507/endocrj.EJ15-0289. View

18.

Oyagbemi A, Odetola A . Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage. Pharmacognosy Res. 2013; 5(4):260-4. PMC: 3807990. DOI: 10.4103/0974-8490.118817. View

19.

Merino-Sanjuan M, Catalan-Latorre A, Nacher A, Miralles-Arnau S, Jimenez-Torres N . Animal model of undernutrition for the evaluation of drug pharmacokinetics. Nutr Hosp. 2012; 26(6):1296-304. DOI: 10.1590/S0212-16112011000600016. View

20.

Adams E, Scragg J . Serum vitamin B12 concentrations in megaloblastic anemia associated with kwashiorkor and marasmus. J Pediatr. 1962; 60:580-5. DOI: 10.1016/s0022-3476(62)80122-x. View