|Year : 2013 | Volume
| Issue : 4 | Page : 260-264
Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage
Ademola A Oyagbemi1, Adebimpe A Odetola2
1 Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine; Department of Biochemistry, College of Medicine, University of Ibadan, Oyo State, Nigeria
2 Department of Biochemistry, College of Medicine, University of Ibadan, Oyo State, Nigeria
|Date of Submission||11-Sep-2012|
|Date of Decision||13-Feb-2013|
|Date of Web Publication||24-Sep-2013|
Ademola A Oyagbemi
Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Oyo State
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: This study was designed to evaluate the ameliorative and hypocholesterolemic effects of dietary supplementation of Cnidoscolus aconitifolius leaf meal (CALM) on hepatic injury and kidney injury associated with protein energy malnutrition (PEM). Materials and Methods: In this study, PEM was induced in weaning male Wistar albino rats by feeding them with low protein diet for 2 weeks. The effects of several recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed were assessed in PEM rats. Plasma biochemical parameters were assessed as well. Results: After the induction of PEM, results obtained showed significant increase in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total proteins (T.P), total bilirubin (T.Bil), triglycerides, total cholesterol, low density lipoproteins (LDL), blood urea nitrogen (BUN), and creatinine with significant reduction in plasma high density lipoproteins (HDL), albumin, sodium (Na + ), potassium (K + ), chloride (Cl− ), bicarbonate (HC03− ), and phosphate (P04 2− ) in PEM rats. Upon introduction of recovery diets containing 20% soya protein or 20% C. aconitifolius in place of soya protein or 10% soya proteins with 10% C. aconitifolius or commercial rat feed for 4 weeks caused significant (P < 0.05) reduction in plasma values of ALP, ALT, AST, T.bil, T.P., LDL, total cholesterol, triglycerides, BUN, creatinine, and significant increase in HDL and complete restoration of plasma electrolytes. Conclusions: C. aconitifolius in protein deficient diets has a protective role against hepatic injury and renal damage associated with PEM.
Keywords: Cnidoscolus aconitifolius leaf meal, hepatic injury, protein energy malnutrition, plasma biochemistry
|How to cite this article:|
Oyagbemi AA, Odetola AA. Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage. Phcog Res 2013;5:260-4
|How to cite this URL:|
Oyagbemi AA, Odetola AA. Hepatoprotective and nephroprotective effects of Cnidoscolus aconitifolius in protein energy malnutrition induced liver and kidney damage. Phcog Res [serial online] 2013 [cited 2020 Jan 25];5:260-4. Available from: http://www.phcogres.com/text.asp?2013/5/4/260/118817
| Introduction|| |
Protein energy malnutrition (PEM) has been a great source of concern to the developing countries and Sub-Saharan Africa in particular. Poverty, war, famine, and lack of good quality proteins have continued to play a staggering role in the pathogenesis of PEM. This has been reported as a common condition in most developing countries especially Africa including Nigeria, Senegal and in most of the war ravaged countries such as Somalia and Sudan in Africa. , PEM has been reported to be associated with anaemia, peroxidation of unsaturated bonds in the erythrocytes membrane, decreased osmotic fragility, disruption of cholesterol phospholipids ratio due to deficiency of scavenger receptor class B type, hepatic injury, impaired blood coagulation, fatty liver, and renal insufficiency. ,,,,,,, PEM retard growth, cause wasting and suppress host defense in humans and animals. ,,
This current research is aimed at determining the restoration of hepatic injury and kidney damage associated with PEM by the consumption of Cnidoscolus aconitifolius leaf meal. C. aconitifolius is a perennial shrub that belongs to the family Euphorbiaceae. It is commonly found in the tropics and sub-tropical region worldwide. It is commonly eaten as soup condiment in southwestern Nigeria specifically Lagos and Oyo States, where it is nick-named as "Iyana Ipaja." Its nutritional and antibacterial activities have recently been reported. , In our laboratory, the phytochemical screening, hepatoprotective, anti-inflammatory, and analgesic properties and the effect of C. aconitifolius against multi-drug resistant microorganism have been reported.  This study therefore illuminates the therapeutic significance of C. aconitifolius in liver and renal damage.
| Materials and Methods|| |
The plant was harvested fresh between October and December 2007 in Ibadan, Oyo State, Nigeria and air-dried at room temperature. It was later identified and authenticated at the herbarium of the Department of Botany and Microbiology, University of Ibadan.
Animals and diets
Forty weaning male Wistar albino rats (Rattus norvegicus) were obtained from the experimental animal house of Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan and were maintained under controlled conditions of light (12-h light/dark cycle) and temperature (30 ± 1 o C). PEM was induced according to a standard method. 
The composition of the malnourished diet is shown in the [Table 1]. After 14 days of inducing PEM, seven rats from each group were sacrificed. The remaining rats in the PEM groups were grouped into three and fed with recovery diets [Table 2] for 4 weeks while the forth group constitutes the animals that did not go through the PEM effects. Group A were fed with diet containing 10% of C. aconitifolius plus 10% soya meal, group B with 20% of C. aconitifolius without soy, group C with 20% of soya meal alone, and group D with commercial feed preparation from Ladokun feeds Nigeria Limited [Table 1].
|Table 2: Plasmas enzymes and proteins post-treatment of PEM rats with different recovery diets. (n = 5)|
Click here to view
All animals received humane care according to the criteria outline in the Guide for the Care and the Use of Laboratory Animals prepared by the National Academy Science and published by the National Institute of Health (USA). The ethic regulations have been followed in accordance with national and institutional guidelines for the protection of animals' welfare during experiment.  The experiment was conducted at Biochemistry Laboratory, Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria. The experimental animals were kept at the experimental unit of the faculty.
Blood sample collection and analysis
Blood was collected from the rats through the retro-orbital venous plexus into lithium heparinised tubes. The rats were first anaesthetized with ether to make blood collection easier. The blood was centrifuged at 4,000 revolutions per minute (rpm) for 10 min. The plasma was later separated with Pasteur pipette for analysis of plasma enzymes that included alkaline phosphatise (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein, total bilirubin, total cholesterol, HDL, LDL, and triglyceride. ,,,,,,, Plasma sodium (N + ), potassium (K + ), and phosphate (P04 2− ) ions were determined by flame photometry. The concentration of K + was calculated using the standard calibration method of Kolthoff and Elving.  Bicarbonate (HC03− ) and Chloride (Cl) anions were measured as described by Van Slyke and Aullen and Schales, respectively. ,,
The data were expressed as mean ± standard error of means (SEM). The test of significance between treated groups and the control was determined by the student t-test at P < 0.05. 
| Results|| |
The effects of C. Aconitifolius on malnourished rats
Initial results obtained before the introduction of recovery diets showed significant P < 0.01 increase in ALP, AST, T.P, and Alb. of malnourished rats as compared to the control [Table 2]. There was increase in values of T.Bil and ALT, but the increase was not significant. There was also significant increase ( P < 0.01) in total cholesterol, triglyceride, and LDL and significant reduction (P < 0.01) in HDL of malnourished rats as compared to normal control [Table 3].
|Table 3: Plasma lipid profiles post treatment of PEM rats with different recovery diets (n = 5)|
Click here to view
The plasma electrolytes obtained from malnourished rats showed significant reduction (P < 0.01) in Na + , Cl− , and significant increase (P < 0.05) for creatinine and (P < 0.01) for urea, respectively, of malnourished rats as compared with normal control [Table 4]. The reduction in the valued of K + , HC03− , and PO4 2− obtained from malnourished rats compared with the control was not statistically significant [Table 2].
|Table 4: Plasmas electrolytes levels post-treatment of PEM rats with different recovery diets (n = 5)|
Click here to view
The effects of recovery diets on plasma enzymes and electrolytes
The inclusion of 20% and 10% CALM recovery diets of C. aconitifolius without soy and with 10% soy produced significant reduction (P < 0.001) in ALP, ALT, and AST when compared with the commercial feed preparation. Supplementation of 20% soy also produced significant reduction (P < 0.01) in both ALP and AST and significant reduction (P < 0.01) in ALT values. There was no significant difference in the values of T.P and albumin between the groups on recovery diets and the control [Table 2].
Also, 20% of CALM inclusion without soy produced significant reduction (P < 0.01) in T. C., TAG, and LDL as compared with the values obtained from animals on commercial feed preparation, and 10% CALM inclusion with 10% soy significantly reduced (P < 0.01) in TAG and LDL as compared with the values obtained from animals on commercial feed preparation. Moreover, 10% CALM inclusion with 10% soy also significantly increased (P < 0.05) HDL and 20% of CALM without soy significantly increased (P < 0.01) HDL when compared with other recovery diets, respectively [Table 3].
There was increase in plasma of Na + values of the groups that received 20% of CALM without soy and soy without C. aconitifolius, but these values were not significant. There was also both significant reduction (P < 0.001) in plasma values of K + and HCO3− (P < 0.05) in animals that were administered 20% CALM without soy and 10% CALM inclusion with 10% soy HCO3− (P < 0.05) when compared to rats that received commercial feed preparation. There was also significant increase (P < 0.05) in both plasma values of PO4 2− of animals on 20% CALM inclusion without soy and 10% CALM with 10% soy supplementation when compared with commercial feed preparation, respectively. Both 20% of CALM without soy and 10% CALM with 10% soy supplementation completely restored the plasma electrolytes to normal, with the exception of plasma Na + and K + plasma concentration. Plasma creatinine values were significantly reduced with the supplementation of 20% CALM inclusion without soy and 10% CALM with 10% soy and 10% soy alone at P < 0.05, P < 0.01, and P < 0.01, respectively [Table 4]. Results obtained show significant reduction in the plasma values of urea at P < 0.001 for 20% CALM inclusion without soy and 10% CALM with 10% soy at P < 0.001 [Table 4]. Moreover, 10% CALM, 20% CALM, and 10% soy alone also significantly reduced plasma creatinine at P < 0.05, P < 0.01, and P < 0.01, respectively [Table 4].
| Discussion|| |
The significant increase in the values of ALT, AST, ALP, total protein, and total bilirubin and significant reduction in albumin obtained in malnourished rats in this work is an indication of extensive damage to the liver and kidney due to induction of PEM. Biochemical parameters ranging from hypoalbuminaemia, anaemia with significant increase in serum ALT, and AST in PEM have been extensively discussed.  Hypoalbuminaeinia alone, as observed in the PEM rats, has also been reported. ,,, Taken together, these results therefore corroborate the aberrations in liver enzymes, total protein, and albumin that are obtained in PEM rats. The three recovery diets show similar hepato-protective effects in malnourished rats after supplementation.
According to this work, PEM also resulted in significant increase in total cholesterol, triglycerides, and lower density lipoproteins and significant reduction in HDL. The alteration in these lipid profiles caused by PEM shows that PEM could be a predisposing factor to coronary heart disease (CHD) in malnourished individuals. The aberration in lipid profiles was corrected with supplementation of 20% CALM inclusion without soy and 10% CALM with 10% soy. Inclusion of soya meal in protein deficient diet slightly corrected the elevated plasma lipid, but could not ameliorate increased LDL.
The increase in blood urea nitrogen (BUN) and creatinine indicates the impairment of kidney function because of PEM. The impairment of kidney function as shown by elevated BUN and creatinine, which are associated with PEM has also been reported.  Different recovery diets were able to ameliorate the abnormally increased BUN and creatinine, but pronounced effect was observed from the animals that received 20% CALM inclusion without soy and 10% CALM with 10% soy.
The plasma electrolytes were also significantly reduced by induction of PEM. The electrolytes depleted are Na + , K +],[ Cl− , HC03− , and P04 2− . These electrolytes are implicated in homeostasis and metabolic function and their depletion can result in grave metabolic disorders. The depletion in serum electrolytes has been reported to be associated with PEM. ,
The depletion observed in plasma electrolytes was adequately restored post-treatment with various recovery diets as compared to control animals. The plasma sodium, chloride, and phosphate ions were completely replenished with 10% and 20% CALM inclusion and soy meal supplementation. On the other hand, potassium ions could not be completely restored by any of the recovery diets; this might be due to the duration of experiment. Soy meal was much effective in restoring plasma bicarbonate to near normal values. Therefore, inclusion of 10% and 20% CALM alone or with 20% soy meal could be used to ameliorate and rejuvenate electrolyte loss or imbalance that is associated with gastrointestinal disorders such as vomiting and diarrhoea. Our laboratory worked extensively medicinal properties and toxicities that might be associated with this plant in question. ,,,,,,
In conclusion, the current research demonstrated that the hepatic and kidney damage that are associated with PEM could be ameliorated with 10% and 20% CALM alone or with 20% soy meal inclusion in protein deficient diets especially in poverty ravage countries in Sub-Saharan Africa. Similarly, 10% and 20% CALM alone or with 20% soy meal could also be substituted in the diets of patients suffering from gastrointestinal disturbances. The cholesterol lowering properties of C. aconitifolius could be potentially utilized to ameliorate CHD in malnourished individuals. This benefit is outstanding in this work. The concentration of plasma creatinine and BUN was also maintained at low level with the supplementation of 10% and 20% CALM or with 20% soy meal. Hence, different recovery diets as shown in this research have nephro-protective effect. Further studies are needed to confirm the antioxidant activities of C. aconitifolius and the possible underlying mechanisms that are associated with the hepato and nephro-protective effects. This plant is cheaper and serves as an alternative source of novel plant protein to soy bean.
| References|| |
|1.||Nnakwe N. The effect and causes of protein-energy malnutrition in Nigerian children. Nutr Res 1995;15:785-94. |
|2.||Idohou-Dossou N, Wade S, Guiro AT, Sarr CS, Diaham B, Cisse D, et al. Nutritional status of preschool Senegalese children: Long-term effects of early severe malnutrition. Br J Nutr 2003;90:1123-32. |
|3.||Borelli P, Blatt S, Pereira J, deMaurino BB, Tsujita M, desonja AC, et al. Reduction of erythroid progenitors in protein-energy malnutrition. Br J Nutr 2007;97:307-14. |
|4.||Brzezinzka-Slebodzinska E. Erythrocytes osmotic fragility test as the measure of defence against free radicals in rabbits of different age. Acta Vet Hung 2001;49:413-19. |
|5.||Ramanadhan M, Kaplay SS. Erythrocytes osmotic fragility protein energy malnutrition: Cholesterol, phospholipids and Ca2+, Mg2+ adenosine triphosphate. Biochem Med 1982;27:226-31. |
|6.||Meurs I, Hoeksra M, van Warooij EJ, Hildebrand RB, Kuiper J, Kuiper F, et al. HDL cholesterol level are important factors for determining the life span of erythrocytes. Exp Hematol 2005;33:1309-19. |
|7.||Rana S, Sodhi CP, Mehta S, Vaiphei K, Katyal R, Thakur S, et al. Protein energy malnutrition and oxidative injury in growing rates. Hum Exp Toxicol 1998;15:81-14. |
|8.||Chang YL, Sohn HS, Chan KC, Berdanier CD, Hargrove JL. Low dietary protein impairs blood coagulation in BHE/cdb rats. J Nutr 1997;127:1279-83. |
|9.||Etukudo MH, Agbedana EO, Akinyinka OO, Osifo BO. Plasma electrolytes total cholesterol, liver enzymes status in protein energy malnutrition. Afr J Med Sci 1999;28:81-5. |
|10.||Chandnas SM, Kulinskaya E, Farrington K. A dramatic reduction of normalized protein catabolic rate occurs late in the course of progressive renal insufficiency. Nephro Dial Transplant 2005;20:2130-38. |
|11.||Kopple JD. Pathophysiology of protein-energy wasting in chronic renal failure. J Nutr 1999;129:2475-515. |
|12.||Redmond HP, Shon J, Kelly CJ, Leon P, Daly JM. Protein calorie malnutrition impairs host defense against Candida albicans. J Surg Res 1991;50:552-55. |
|13.||Sayed-el N, Mohammed AG, Nofal L, Mahfouz A, Zeid HA. Malnutrition among pre-school children in Alexandria, Egypt. J Health Popul Nutr 2001;19:275-80. |
|14.||Ganiyu O. Effect of some post-harvest treatment on the nutritional properties of Cnidoscolus aconitifolius leaf. Pak J Nutr 2005;4:226-30. |
|15.||Awoyinka AO, Balogun IO, Ogunnowo AA. Phytochemical screening and in vitro bioactivity of Cnidoscolus aconitifolius (Euphorbiaceae). J Med Plant Res 2007;1:063-65. |
|16.||Adaramoye AO, Aluko A, Oyagbemi AA. Cnidoscolus aconitifolius leaf extract protects against hepatic damage induced by chronic ethanol administration in Wistar rats. Alcohol Alcohol 2011;46:451-8. |
|17.||Adelusi SA, Olowokere JO. A rapid method of induction of post-natal protein-energy malnutrition (PEM) in laboratory animals. Niger J Appl Sci 1985;3:171-4. |
|18.||PHS (Public Health Service). Public health service policy on humane care and the use of laboratory animals. US Department of Health and Humane Services, Washington DC, USA. 1996:99-158. |
|19.||Tietz NW, Shuey DF. Reference intervals for alkaline phosphatise activity determined by the IFCC and AACC reference methods. Clin Chem 1986;32:1593-4. |
|20.||Bergmeyer HU, Horder M, Rej R. Approved recommendation of IFCC methods for the measurement of catalytic concentration of enzymes. Part 3. IFCC method for alanine aminotransferase. J Clin Chem Clin Biochem 1985;24:418-89. |
|21.||Klauke R, Schmidt E, Lorentz K. Recommendations for carrying out standard IFCC procedures for the catalytic concentrations of creatinine kinase aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase at 37C. Standardization Committee of the German Society for Clinical Chemistry, Enzyme Working Group of the Ferman Society for Clinical Chemistry. Eur J Clin Chem Clin Biochem 1988;31:901-9. |
|22.||Keller A. Total Serum protein. In: Kaplan LA, Pesce AJ, editors. Clinical Chemistry, Theory, Analysis, and Correlation. St. Lious: Mosby Company, USA; 1984. |
|23.||Schlebusch H, Schneider C, Liappis N. Bilirubin determination in neonatal sera: Precision, accuracy and sensitivity to hemoglobin interferences of six routine methods. Clin Chem 1995;41:95. |
|24.||Abell L, Levy BB, Brodie BB, Kendall FE. A sample method for the estimation plasma total cholesterol in serum and demonstration of its specificity. J Bio Chem 1995;357-66. |
|25.||Warnick GR, Albers JJ. Heparin Mg2+ quantitation of high density lipoprotein cholesterol. An ultra-filtration procedure for lipemic samples. Clin Chem 1978;24:900-4. |
|26.||Fredickson DS, Levy RI, Lindgren FP. A comparison of irritable abnormal lipoprotein patterns as defined by two different techniques. In Clin Zuvest 1968;47:2446-57. |
|27.||Van HE, Zilversmit DB. Micro-method for the direct determination of plasma triglyceride. J Lab Clin Med 1957;50:152-7. |
|28.||Kolthoff IM, Elving PJ. Treatise on analytical chemistry; part I and II. John Wiley and Sons. 1976;15:15-105. |
|29.||van Slyke W, Aulle HS. Text book of clinical chemistry Philadelphia W. S. Co. 1977; 112-97. |
|30.||Schales O, Schales S. Determination of chloride in Laboratory. J Biol Chem 1971;140:879. |
|31.||Bailey NT. Statistical Methods in Biology. 2nd ed. Cambridge University Press, Cambridge; 1992. |
|32.||Taiwo OO, Thomas KD. Plasma biochemical parameter in Nigeria children with protein energy malnutrition. East Afr Med J 1992;69:428-32. |
|33.||Ibrahim SA, Eltom AM, Abdul-Rahman AM, Saeed BO. Correlation of some biochemical parameters with clinical features of protein energy malnutrition. East Afr Med J 1994;71:77-82. |
|34.||Dufor DR. Effects of food ingestion on routine Laboratory tests. Clin Chem 1998;4461-36. |
|35.||Young DS. Effects of Pre-analytical Variables on Clinical Laboratory Test, 2nd ed. Washington, DC: AACC Press; 1997. |
|36.||Jan N, Sydney Y. Creatinine and creatine clearance. Healthwise Incorporated; 2006. |
|37.||Oyagbemi AA, Odetola AA. Hepatoprotective effects of ethanolic extract of Cnidoscolus aconitifolius on paracetamol induced-hepatic damage in rats. Pak J Biol Sci 2010;13:164-9. |
|38.||Azeez OI, Oyagbemi AA, Oyeyemi MO, Odetola AA. Ameliorative effects of Cnidoscolus aconitifolius on anaemia, erythrocyte osmotic fragility, and abnormal sperm morphometry in alloxan-treated Wistar rats. Afri Health Sci 2010;10:283-91. |
|39.||Oyagbemi AA, Ogunleye AO, Lawal TO, Azeez IO. The effects of Cnidoscolus aconitifolius to multi-drug resistant micro-organism (in vitro). Afri J Biotech 2011;10:413-5. |
|40.||Oyagbemi AA, Odetola AA, Azeez OI. Phytochemical investigation and proximate analysis on the leaves of Cnidoscolus aconitifolius. J Med Food 2011;14:322-4. |
|41.||Onasanwo SA, Oyagbemi AA, Saba AB. Anti-inflammatory and analgesic properties of the ethanolic extract of Cnidoscolus aconitifolius in rats and mice. J Basic Clin Physiol Pharmacol 2011;22:37-41. |
|42.||Saba AB, Oyagbemi AA, Azeez OI. Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by ethanolic leaf extract of Cnidoscolus aconitifolius (EECA) in rats. Niger J Physiol Sci 2011;25:139-47. |
|43.||Adaramoye AO, Aluko A, Oyagbemi AA. Cnidoscolus aconitifolius leaf extract protects against hepatic damage induced by chronic ethanol administration 2011;46:451-8. |
[Table 1], [Table 2], [Table 3], [Table 4]
|This article has been cited by|
||Phytochemical and pharmacological aspects of Cnidoscolus Pohl species: a systematic review
| ||Raimundo Gonçalves de Oliveira-Júnior,Christiane Adrielly Alves Ferraz,Ana Paula de Oliveira,Camila Souza Araújo,Layanne Feitosa da Silva Oliveira,Laurent Picot,Larissa Araújo Rolim,Pedro José Rolim-Neto,Jackson Roberto Guedes da Silva Almeida |
| ||Phytomedicine. 2017; |
|[Pubmed] | [DOI]|
||Tanshinone IIA protects against pulmonary arterial hypertension in broilers
| ||Guoliang Hu,Yalu Song,Shanlin Ke,Huabin Cao,Caiying Zhang,Guangfu Deng,Fei Yang,Sihui Zhou,Pei Liu,Xiaoquan Guo,Ping Liu |
| ||Poultry Science. 2016; : pew322 |
|[Pubmed] | [DOI]|