|
|
ORIGINAL ARTICLE |
|
Year : 2017 | Volume
: 5
| Issue : 1 | Page : 9-13 |
|
Histomorphological effects of nicotine on the kidney
Emmanuel Igho Odokuma, Joan Eseoghene Adogbeji
Department of Human Anatomy and Cell Biology, Delta State University, Abraka, Nigeria
Date of Web Publication | 11-Jul-2017 |
Correspondence Address: Emmanuel Igho Odokuma Department of Human Anatomy and Cell Biology, College of Health Sciences, Delta State University, Abraka Nigeria
![Login to access the Email id](http://www.medknow.com/images/email.gif) Source of Support: None, Conflict of Interest: None ![Crossref citations](http://www.medknow.com/journals/images/crossref.png) | Check |
DOI: 10.4103/2315-7992.210254
Introduction: This experimental animal study was designed to investigate the histomorphological effects of nicotine on the kidneys of matured adult Wistar rats. Materials and Methods: Permission for the study was obtained from the Department of Human Anatomy and Cell Biology Ethics Committee (DELSU/CHS/ANA/68/43), and it involved 36 rats which were randomly assigned into three test and one control group. While animals in the control group (Group A) received only water and feed, 2 mg/day, 4 mg/day, and 6 mg/day of pure nicotine in solution was orally administered to test Groups B, C, and D, respectively (dose: 50 mg/kg/day). At the end of 7, 21, and 42 days, one experimental animal was selected from each of the groups at random, euthanized, and the harvested kidneys processed by standard techniques The obtained tissue samples were viewed with a digital light microscope (Scopetek DCM 500, 20.0 mega pixel) connected through a USB to an HP computer. Results: The control group showed normal histomorphologic features, but the test groups which were dose and time dependent showed progressive histological alterations. Glomerulosclerosis and widening of the glomerular space were observed following acute and subacute exposure unlike with the chronically exposed rats in which an intact renal structural integrity was documented. Conclusion: This study that prolonged exposure to orally administered nicotine within normal doses had minimal effects on the kidneys of adult Wistar rats. Keywords: Acute, chronic, histology, kidney, nicotine
How to cite this article: Odokuma EI, Adogbeji JE. Histomorphological effects of nicotine on the kidney. Ann Bioanthropol 2017;5:9-13 |
Introduction | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
Nicotine has been defined as a potent acetyl cholinergic alkaloid found in the leaves of the nightshade family plants, Solanaceae.[1] The natural product of tobacco has been documented to occur in these leaves in which and constitutes about 0.6–3.0% of the dry weight of the plant Nicotinia tobacom.[2] It has been reported that nicotine is commonly ingested as a powdered form called “tobacco snuff” which is either inhaled (sniffed) through the nose or ingested orally [3] nicotine has been demonstrated to display stimulant functions which at high dose and chronic ingestion, may display toxic and addictive effects.[4] This agent is the active ingredient in most cigarettes which when inhaled passes from the lungs to the brain within seconds and immediately stimulates the release of many chemical messengers.[5],[6]
The presence of renal nicotinic acetylcholine receptor (nAChR) has been documented to enable the actions of nicotine on the kidney with subsequent excretion in urine.[7],[8] This agent has been revealed to enhance vasoconstriction thereby modulating arterial blood pressure with resultant glomerular hypertension,[9] whereas another study explained that long-term oral administration of nicotine preserved renal function and reduced inflammation in rats with progressive kidney.[10] Though some studies have however demonstrated that nicotine containing products like tobacco may have been implicated in the formation of malignant renal neoplasms,[11],[12] these sources of nicotine (e.g., tobacco), however, contain complexes which may act in synergy or in antagonism with nicotine. Since the specific effect of nicotine on the kidneys have rarely been reported, the index study was directed at investigating the acute, subacute, and chronic histomorphological effects of nicotine on renal histoarchitecture. This study will create awareness on the possible effects of nicotine, on the kidneys, thus educating the users of this agent, which is present in several popular house hold beverages.
Materials and Methods | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
Materials
Animal handling
The experiment involved 36 adult Wistar rats of both sexes (18 males and 18 females), weighing between 100 and 20 and obtained from animal house in the Department of Human Anatomy and Cell Biology, Faculty of Basic Medical Science, Delta State University, Abraka.
Ethical considerations
Approval for this study was obtained from the Ethics Committee of the Department of Human Anatomy and Cell Biology, Delta State University, Abraka, with protocol number DELSU/CHS/ANA/68/43, and it conformed to the provision of the Declaration of Helsinki.[13]
Pharmacological agent
About 25 grams of nicotine hydrogen salt tartrate (95% nicotine);[14] Sigma life science 614-002-00-x United Kingdom, which was purchased from Rovet Scientific shop in Benin-City, Edo State, Nigeria.
Methodology
The animals were divided randomly into four groups (one control and three test groups), all of which were fed with growers mash and water ad libidum.[15],[16],[17] The test agent was orally administered to the experimental groups, furthers divided into B, C, and D based on the dose of nicotine administered, each consisting of eight animals.
The lethal orals dose for nicotine in rats has been demonstrated to be 50 mg/kg per body weight [18] and the recorded experimental animal weights ranged between 100 and 200 g. Animals in Groups B, C, and D received 2 mg, 4 mg, and 6 mg of nicotine, respectively.[19] The agent was administered 12 h to achieve a regular plasma concentration. The experiment lasted for 42 days.[20]
Method of tissue collection
One control and two test animals were selected from test Groups B, C, and D, respectively, at the end of the 7th, 21st, and 42nd day, (to assess the effects of the studies calculated doses nicotine during each of these periods). The experimental models were weighed and euthanized by cervical dislocation. Incisions were made from the chin vertically to the pubic quadrant. The kidneys which were then carefully harvested from the retroperitoneum, weighed, and fixed in 10% formaldehyde.[21] Following cut-up, sections of kidneys were placed in tissue cassettes and processed by standard histological procedures.[21] Slides were viewed with a digital light microscope eye piece Scopetek DCM 500, 5.0 Mega pixel connected by USB 2.0 to a computer.
Results | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
Control group for days 7, 21 and 42
As displayed in Figures a1-c1, the slides of the control group in the corresponding days are shown. The micrographs show intact histo and cytoarchitectural features of the kidneys. These are features of normal renal parenchyma.
Test group 1: Day 7
As displayed in Figures a2-c2, for rats exposed to 2 mg, 4 mg, and 6 mg of nicotine for 7 days, sections of the kidneys were composed of several variably sized renal tubules separated by a loose connective tissue stroma in which were few blood vessels. The bowman's spaces were lined by flattened epithelium. Within the intervening, vaguely lobulated glomeruli were few capillaries and mesangial cells. There was mild interstitial intraglomerular vascular congestion and glomerular collapse, but renal pelvis was intact. These features were in keeping with mild renal congestion.
Test group 2: Day 21
As displayed in Figures a3-c3 for rats exposed to 2 mg, 4 mg, and 6 mg nicotine for 21 days, sections of the kidney were composed of a cortex and a medulla. There was marked distortion of the glomeruli with several foci of glomerulosclerosis. The medullary ducts were present but were lined predominantly by flattened epithelial cells. Majority of the blood vessels displayed moderate congestion.
Test group 3: Day 42
As displayed in Figures a4-c4, rats exposed to 2 mg, 4 mg, and 6 mg nicotine for 42 days showed sections of the kidney composed of a cortex, medulla, and minor calyx.
Several glomeruli were present within the cortex intermixed with renal tubules both of which had normal histo- and cyto-architectural features. The medullary ducts were separated by a thin connective tissue stroma in which were thin walled blood vessels. The calyces were lined by a transitional epithelium. The observed findings were in keeping with normal renal parenchyma.
Discussion | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
The index study has demonstrated that acute (7 day) oral administration of nicotine mildly disrupted the histological and cytological organization of the kidney. There was a dose-dependent mild increase in bowman's space and vascular congestion when compared with the control group. This alteration which could be attributed to the vasoconstrictive potential of nicotine on the blood vessels by suppressing the production of an important vasodilator (nitric oxide),[22] correlated positively with the report of a previous finding.[23] Increases in bowman's space may compromise the ultra-filtrating functions of the glomeruli by simultaneous shrinking of the glomeruli resulting in a decrease in glomerular filtration rate. The findings were in tandem with a previous study which reported that persistent exposure to nicotine altered renal function ultimately progressing to renal disease.[22] This was however unlike Agarwal et al.'s report were nicotine, was documented to be renoprotective, albeit, following prolonged nicotine exposure.[10] The observed differences may therefore not be unrelated with the differences in duration of both studies which may further indicate the time dependent effects of the agent.![](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Farticles%2F2017%2F5%2F1%2Fimages%2FAnnBioanthropol_2017_5_1_9_210254_i1.jpg)
![](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Farticles%2F2017%2F5%2F1%2Fimages%2FAnnBioanthropol_2017_5_1_9_210254_i2.jpg)
![](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Farticles%2F2017%2F5%2F1%2Fimages%2FAnnBioanthropol_2017_5_1_9_210254_i3.jpg)
![](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Farticles%2F2017%2F5%2F1%2Fimages%2FAnnBioanthropol_2017_5_1_9_210254_i4.jpg)
The mild interstitial intraglomerular congestion, which was observed in the experimental groups further buttressed the likelihood that nicotine affected the pressure within the renal corpuscle which was similar to a previous finding were nicotine was reported to potentiate glomerular hydrostatic pressure.[22] Previous studies have also reported that exposure to nicotine for 2–3 weeks was suitable to produce deleterious effect on the kidney.[24],[25] The mechanisms by which this damages occurred were however obscure. From this study, however, it could be inferred that nicotine may act via extensive stimulation of renal stromal rTest group 1: Day 7 eceptors.[26] Although another author concluded that the mechanism of action was by damage to the renal tubules and blood vessels,[27] vague understanding of the specific mechanisms responsible for this observation has however been noted by others.[27],[28]
It was further revealed that animals exposed to nicotine for 42 days showed no morphological or histological alterations in the experimental group when compared with the control group. Sections from the chronically exposed experimental groups had a better histological profile when compared with those of day's 7 and day's 21. The normal histo- and cyto-architecture observed in the experimental group was an indication that prolonged oral consumption of nicotine were not be nephrotoxic which corroborated reports of Agarwal et al. in which long-term oral nicotine were observed to improve renal morphology as well as reduce renal inflammation.[10]
The extensive glomerulosclerosis and increase in intra glomerular and interstitial space as well as vascular damages which were evident at day 7 and day 21 was however not present in day 42, it may therefore be inferred, unlike previously reported, that chronic exposure to nicotine may display scant nephrotoxicity.
Conclusion | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
Result from this study has shown that long-term oral administration of nicotine preserved normal renal morphology.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | | ![Top](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Farrow_top.gif) |
1. | Karaconji IB. Facts about nicotine toxicity. Arh Hig Rada Toksikol 2005;56:363-71. ![Back to cited text no. 1](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
2. | Hoffman D. Chemistry and Toxicology In: Klauser MD. Cigars; Health Effects and Trends. National Cancer Institute 2012;9:57-8. |
3. | Ureme SO, Ibeagha ID, Maduka IG, Ibeagbulam OG. The concentrations of methaemoglogin, carboxyhaemoglobin and some haematological parameters in tobacco snuff addicts in Igbo of Nigeria. Niger J Physiol Sci 2007;22:27-32. ![Back to cited text no. 3](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
4. | Hatsukami DK, Severson HH. Oral spit tobacco: Addiction, prevention and treatment. Nicotine Tob Res 1999;1:21-44. ![Back to cited text no. 4](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
5. | Pomerleau OF, Rosecrans J. Neuroregulatory effects of nicotine. Psychoneuroendocrinology 1989;14:407-23. ![Back to cited text no. 5](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
6. | Rusted J, Graupner L, O'Connell N, Nicholls C. Does nicotine improve cognitive function? Psychopharmacology (Berl) 1994;115:547-9. |
7. | Feng S, Kapur S, Sarkar M, Muhammad R, Mendes P, Newland K, et al. Respiratory retention of nicotine and urinary excretion of nicotine and its five major metabolites in adult male smokers. Toxicol Lett 2007;173:101-6. ![Back to cited text no. 7](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
8. | Agarwal PK, Hellemons ME, Zelle DM, van Ree RM, van den Born J, van der Heide JJ, et al. Smoking is a risk factor for graft failure and mortality after renal transplantation. Am J Nephrol 2011;34:26-31. ![Back to cited text no. 8](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
9. | Goodman MT, Morgenstern H, Wynder EL. A case-control study of factors affecting the development of renal cell cancer. Am J Epidemiol 1986;124:926-41. ![Back to cited text no. 9](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
10. | Agarwal PK, van den Born J, van Goor H, Navis G, Gans RO, Bakker SJ. Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria. Am J Physiol Renal Physiol 2012;302:F895-904. ![Back to cited text no. 10](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
11. | Muscat JE, Hoffmann D, Wynder EL. The epidemiology of renal cell carcinoma. A second look. Cancer 1995;75:2552-7. ![Back to cited text no. 11](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
12. | Ritz E, Benck U, Franek E, Keller C, Seyfarth M, Clorius J. Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease. J Am Soc Nephrol 1998;9:1798-804. ![Back to cited text no. 12](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
13. | Animal Research Ethics: A Handbook of USP Researchers. Vol. 2. South Pacific: Research Office Publishers; 2005. p. 3-4. |
14. | Oyeyipo IP, Raji Y, Emikpe BO, Bolarinwa AF. Effects of nicotine on sperm characteristics and fertility profile in adult male rats: A possible role of cessation. J Reprod Infertil 2011;12:201-7. ![Back to cited text no. 14](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
15. | Bellhorn RW. Lighting in the animal environment. Lab Anim Sci 1980;30 (2 Pt 2):440-50. |
16. | Obernier JA, Baldwin RL. Establishing an appropriate period of acclimatization following transportation of laboratory animals. ILAR J 2006;47:364-9. ![Back to cited text no. 16](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
17. | Kasane IHE, Inhila KJ, Nevalainen JI, Valsanen SB, Mertanen AMO, Mering SM, et al. A novel dietary restriction method for group-housed animals: Weight gain and clinical chemistry characterization. R Soc Med J 2009;43:138-48. |
18. | Klassen CD, Amdur MO, Doull J. Casarett and Doull's Toxicology: The Basic Science of Poisons. 5 th ed. New York: McGraw-Hill; 1995. |
19. | Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol 2014;88:5-7. ![Back to cited text no. 19](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
20. | Hukkanen J, Jacob P 3 rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev 2005;57:79-115. |
21. | Culling CF. Handbook of Histopathological and Histochemical Techniques. 3 rd ed., Vol. 5. London: Butterworth and Co. Limited; 1974. p. 73-109. |
22. | Gabbai FB, Khang SJ. Effect of nicotine administration on glomerular heamodynamic in normal rats with experimental diabetes. J Am Soc Nephrol 2001;12:253. |
23. | Adedayo AD, Tijani AA, Musa AA, Adeniyi TD. Histological study of smoke extract of tobacco nicotiana on the heart, liver, lungs, kidney, and testes of male Sprague-Dawley rats. Niger Med J 2011;52:217-22. [Full text] |
24. | Orth SR, Ritz E. The renal risks of smoking: An update. Curr Opin Nephrol Hypertens 2002;11:483-8. ![Back to cited text no. 24](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
25. | Halimi JM, Mimran A. Renal effects of smoking: Potential mechanisms and perspectives. Nephrol Dial Transplant 2000;15:938-40. ![Back to cited text no. 25](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
26. | Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, et al. Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. FEBS J 2007;274:3799-845. ![Back to cited text no. 26](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
27. | Tamaoki L, Oshiro-Monreal FM, Helou CM. Effects of nicotine exposure on renal function of normal and hypercholesterolemic rats. Am J Nephrol 2009;30:377-82. ![Back to cited text no. 27](/ServeContent?url=http%3A%2F%2Fwww.bioanthrojournal.org%2Fimages%2Fref_top.gif) [ PUBMED] |
28. | Budisavljevic MN, Ploth DW. Nicotine and the kidney: Mr. Hyde, and perhaps some Dr. Jekyll. Am J Physiol Renal Physiol 2012;302:F1082-3. |
|